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Int. j. cardiovasc. sci. (Impr.) ; 35(2): 214-219, Mar.-Apr. 2022. tab
Article in English | LILACS | ID: biblio-1364976


Abstract Background Various studies are ongoing related to the radioprotective agents. Herbal preparations are currently becoming popular because of their beneficial effects with fewer side effects compared to the synthetic/semi-synthetic medicines, and Nigella sativa oil (NSO) is only one of them. Objective To investigate NSO for its antioxidant effects on the heart tissue of rats exposed to ionizing radiation (IR). Methods Thirty six male albino Wistar rats, divided into four groups, were designated to group I (IR plus NSO group) that received both 5 Gray of gamma IR to total cranium and NSO; group II (IR alone group) that received IR plus saline, group III (control group of NSO) that received saline and did not receive NSO or IR; group IV (control group) that received only sham IR. Alterations in Total antioxidant status (TAS) and Total oxidant status (TOS), Oxidative stres index (OSI), Sulhydryl group (SH), Lipid hydroperoxide (LOOH), Paraoxonase (PON) levels, Arylesterase (ARE) and Ceruloplasmin (CER) activities in homogenized heart tissue of rats were measured by biochemical methods. Results In heart tissue of the rats in the IR alone group (group II) LOOH, TOS and OSI levels were found to be higher, ARE activity and TAS level were found to be lower than all of the other groups (p < 0.01). These results also support that IR increases oxidative stress and NSO's protective effect. Conclusion NSO would reduce the oxidative damage in the irradiated heart tissue in the experimental rat model.

Animals , Male , Rats , Radiation-Protective Agents/therapeutic use , Plant Oils/therapeutic use , Nigella sativa , Oxidative Stress/drug effects , Heart/radiation effects , Antioxidants/therapeutic use , Plants, Medicinal , Radiation-Protective Agents/analysis , Rats, Inbred Strains , Rats, Wistar , Oxidative Stress/radiation effects , Plant Preparations/therapeutic use , Cardiotoxicity/drug therapy , Heart/drug effects , Phytotherapy
Int. braz. j. urol ; 48(1): 131-156, Jan.-Feb. 2022. tab, graf
Article in English | LILACS | ID: biblio-1356297


ABSTRACT Purpose: Sperm DNA fragmentation (SDF) and seminal oxidative stress are emerging measurable factors in male factor infertility, which interventions could potentially reduce. We evaluated (i) the impact of lifestyle changes combined with oral antioxidant intake on sperm DNA fragmentation index (DFI) and static oxidation-reduction potential (sORP), and (ii) the correlation between DFI and sORP. Materials and Methods: We conducted a prospective study involving 93 infertile males with a history of failed IVF/ICSI. Ten healthy male volunteers served as controls. Semen analysis was carried out according to 2010 WHO manual, whereas seminal sORP was measured using the MiOXSYS platform. SDF was assessed by sperm chromatin structure assay. Participants with DFI >15% underwent a three-month lifestyle intervention program, primarily based on diet and exercise, combined with oral antioxidant therapy using multivitamins, coenzyme Q10, omega-3, and oligo-elements. We assessed changes in semen parameters, DFI, and sORP, and compared DFI results to those of volunteers obtained two weeks apart. Spearman rank correlation tests were computed for sORP and DFI results. Results: Thirty-eight (40.8%) patients had DFI >15%, of whom 31 participated in the intervention program. A significant decrease in median DFI from 25.8% to 18.0% was seen after the intervention (P <0.0001). The mean DFI decrease was 7.2% (95% CI: 4.8-9.5%; P <0.0001), whereas it was 0.42% (95%CI; -4.8 to 5.6%) in volunteers (P <0.00001). No differences were observed in sperm parameters and sORP. Based on paired sORP and DFI data from 86 patients, no correlation was observed between sORP and DFI values (rho=0.03). Conclusion: A 3-month lifestyle intervention program combined with antioxidant therapy reduced DFI in infertile men with elevated SDF and a history of failed IVF/ICSI. A personalized lifestyle and antioxidant intervention could improve fertility of subfertile couples through a reduction in DFI, albeit controlled trials evaluating reproductive outcomes are needed before firm conclusions can be made. Trial registration number and date: NCT03898752, April 2, 2019.

Humans , Male , Infertility, Male/drug therapy , Antioxidants/metabolism , Antioxidants/therapeutic use , Spermatozoa , Fertilization in Vitro , Pilot Projects , Prospective Studies , Oxidative Stress , DNA Fragmentation , Life Style
Rev. Assoc. Med. Bras. (1992) ; 68(1): 87-93, Jan. 2022. tab, graf
Article in English | LILACS | ID: biblio-1360707


SUMMARY OBJECTIVE: The aim of this study was to evaluate the hepatoprotective effect and mechanism of action of artichoke leaf extract in hepatic ischemia/reperfusion injury. METHODS: Rats were divided into three groups such as sham, control, and artichoke leaf extract groups. Antioxidant enzyme activities and biochemical parameters were examined from the tissue and serum obtained from the subjects. Histopathological findings were scored semiquantitatively. RESULTS: Statistically, the antioxidant activity was highest in the artichoke leaf extract group, the difference in biochemical parameters and C-reactive protein was significant compared with the control group, and the histopathological positive effects were found to be significantly higher. CONCLUSIONS: As a result, artichoke leaf extract had a hepatoprotective effect and that this effect was related to the antioxidant and anti-inflammatory effects of artichoke.

Animals , Rats , Reperfusion Injury/prevention & control , Reperfusion Injury/drug therapy , Cynara scolymus , Plant Extracts/therapeutic use , Plant Extracts/pharmacology , Liver , Antioxidants/metabolism , Antioxidants/therapeutic use , Antioxidants/pharmacology
Odontoestomatol ; 24(39): 1-14, 2022.
Article in Spanish | LILACS, BNUY, BNUY-Odon | ID: biblio-1370336


Numerosos reportes demuestran la presencia de biomarcadores de estrés oxidativo en la saliva de fumadores y hay un creciente interés en correlacionar estos procesos moleculares con la etiología de algunas enfermedades orales, como la periodontitis, una enfermedad inmunoinflamatoria crónica relacionada con un desequilibrio de la homeostasis redox celular. Objetivo: realizar una revisión narrativa sobre la relación entre la disminución de la capacidad antioxidante salival inducida por humo de tabaco, la periodontitis y el potencial uso de farmacología redox para el tratamiento de esta patología. Métodos: se realizó una búsqueda bibliográfica en bases de datos como PUBMED (NLM, NIH, NCBI) y SciELO. Resultados: existe evidencia que relaciona la baja capacidad antioxidante salival con un retraso en el restablecimiento de las condiciones normales en la cavidad oral ante el desarrollo de periodontitis. A su vez, el estado inflamatorio asociado colabora sinérgicamente, provocando un mayor daño tisular con pérdida de tejidos de soporte dentario, fenómeno que podría ser modulado por la acción de farmacología redox. Conclusiones: la intervención con farmacología redox, podría atenuar los biomarcadores de progresión de la enfermedad periodontal, constituyendo una herramienta prometedora para utilizar en conjunto con las estrategias de tratamiento tradicionales.

Numerous reports demonstrate the presence of oxidative stress biomarkers in the saliva of smokers and there is a growing interest in correlating these molecular processes with the etiology of some oral diseases, such as periodontitis, a chronic immunoinlammatory disease related to an imbalance of cellular redox homeostasis. Aims: achieve a narrative review on the relationship between the decrease in salivary antioxidant capacity induced by tobacco smoke, periodontitis, and the potential use of redox pharmacology for the treatment of this pathology. Methods: a bibliographic search was carried out in databases such as PUBMED (NLM, NIH, NCBI) and SciELO. Results: there is evidence that relates the low salivary antioxidant capacity with a delay in the reestablishment of normal conditions in the oral cavity before the development of periodontitis. In turn, the associated inflammatory state collaborates synergistically, causing greater tissue damage with loss of dental support tissues, a phenomenon that could be modulated by the action of redox pharmacology. Conclusions: intervention with redox pharmacology could attenuate the biomarkers of periodontal disease progression, constituting a promising tool to be used in conjunction with traditional treatment strategies.

Muitos artigos demonstram a presença de biomarcadores de estresse oxidativo na saliva de fumantes e há um interesse crescente em correlacionar esses processos moleculares com a etiologia de algumas doenças bucais, como a periodontite, uma doença imunoinlamatória crônica relacionada a um desequilíbrio da redox celular homeostase. Objetivo: realizar uma revisão narrativa sobre a relaçã o entre a diminuiçã o da capacidade antioxidante salivar induzida pela fumaça do tabaco, periodontite e o uso potencial da farmacologia redox para o tratamento desta patologia. Métodos: uma pesquisa bibliográica foi realizada usando bases de dados como PUBMED (NLM, NIH, NCBI) e SciELO. Resultados: há evidências que relacionam a baixa capacidade antioxidante salivar com o retardo no restabelecimento das condições normais da cavidade oral antes do desenvolvimento da periodontite. Por sua vez, o estado inflamatório associado colabora sinergicamente, causando maior dano tecidual com perda de tecidos de suporte dentário, fenômeno que poderia ser modulado pela açã o da farmacologia redox. Conclusões: a intervençã o com a farmacologia redox poderia atenuar os biomarcadores de progressã o da doença periodontal, constituindo-se em uma ferramenta promissora para ser utilizada em conjunto com estratégias tradicionais de tratamento.

Humans , Periodontitis/etiology , Periodontitis/drug therapy , Saliva/metabolism , Oxidative Stress , Tobacco Smoking/adverse effects , Antioxidants/therapeutic use , Oxidation-Reduction , Biomarkers , Oxidative Stress/drug effects , Homeostasis
Rev. Soc. Bras. Clín. Méd ; 19(2): 128-138, abr.-jun. 2021.
Article in Portuguese | LILACS | ID: biblio-1379287


O vitiligo é uma desordem dermatológica complexa, cuja patogênese ainda não é totalmente esclarecida. Apesar de não apresentar complicações funcionais no organismo dos pacientes acometidos, o vitiligo pode resultar em um grande impacto psicossocial. Desse modo, é importante que os médicos saibam como conduzir o tratamento dessa patologia. O objetivo deste estudo foi documentar as terapias disponíveis para o tratamento do vitiligo, assim como apontar pesquisas que relataram a utilização dessas opções terapêuticas e os dados resultantes. As terapias abordadas foram corticoides tópicos e sistêmicos, fototerapia e fotoquimioterapias, antioxidantes, imunomoduladores, fenilalanina, despigmentação, procedimentos cirúrgicos e novas abordagens. A monoterapia parece ser menos eficaz no tratamento do vitiligo. A associação de medicação tópica e/ou sistêmica com o uso da fototerapia ultravioleta B de banda estreita parece ser o padrão-ouro para a repigmentação da pele dos pacientes. Medicamentos novos estão em estudo, porém sua eficácia e o estudo dos possíveis efeitos colaterais, principalmente a longo prazo, têm que ser melhores investigados. É necessário que o médico dermatologista, em conjunto com o paciente, escolha a melhor terapia dentre as disponíveis, de acordo com critérios clínicos e a possibilidade de acesso ao tratamento pelo portador. O acompanhamento e a abordagem por uma equipe multiprofissional também são importantes. (AU)

Vitiligo is a complex dermatological disorder, whose pathogenesis has not yet been fully elucidated. Although it does not present functional complications in the affected patients' body, vitiligo can result in a great psychosocial impact. Therefore, it is important that physicians know how to conduct its treatment. This study aimed at documenting the available therapies for the treatment of vitiligo, as well as pointing out studies reporting the use of these therapeutic options and their resulting data. The therapies addressed were topical and systemic corticosteroids, phototherapy, and photochemotherapies, antioxidants, immunomodulators, phenylalanine, depigmentation, surgical procedures, and new approaches. Monotherapy appears to be less effective in the treatment of vitiligo. The combination of topical and/or systemic medication with the use of narrowband ultraviolet B phototherapy seems to be the gold standard for the patients' skin repigmentation. New drugs are under study, but their effectiveness and study of possible side effects, especially in the long run, have to be better investigated. It is necessary that the dermatologist, together with the patient, choose the best therapy among those available, according to clinical criteria and the possibility of access to treatment by the patient. Monitoring and approach by a multiprofessional team is also important. (AU)

Humans , Vitiligo/therapy , Phenylalanine/therapeutic use , Placental Extracts/therapeutic use , PUVA Therapy , Ultraviolet Rays , Vitiligo/surgery , Vitiligo/drug therapy , Vitiligo/radiotherapy , Adrenal Cortex Hormones/therapeutic use , Plant Preparations/therapeutic use , Low-Level Light Therapy , Brosimum gaudichaudii/therapeutic use , Polypodium , Lasers, Excimer/therapeutic use , Lasers, Gas/therapeutic use , Immunologic Factors/therapeutic use , Phytotherapy , Antioxidants/therapeutic use
Arq. bras. med. vet. zootec. (Online) ; 73(2): 311-319, Mar.-Apr. 2021. tab
Article in English | LILACS, VETINDEX | ID: biblio-1248952


The objective of this study was to evaluate the rate of conception, metabolic, and structural conditions of cryopreserved bovine sperm cells, plus extender with IGF-1 and glutathione (GSH). 12 ejaculations of Nelore bulls were used, submitted to treatments: control, gSH (2mM/mL), IGF-1 (100ng/mL) and gSH (1mM/mL) + IGF-1 (50ng/mL). After cryopreservation and thawing the semen passed the fast thermo resistance test (TTR), plasma membrane and acrosomal integrity (PIAI), mitochondrial membrane potential (AP), oxidative stress, and conception rate. Tukey test was used for the statistical analysis of the parametric variables and the Friedman test for nonparametric. The gestation percentage was compared by the Chi-square test. There was no statistical difference (P<0.05) between treatments for the TTRr variable. Otherwise in the oxidative stress evaluated with the CellROX probe was noted that the IGF-1 showed the highest number of reactive cells (P<0.05). The PIAI, AP and gestation rate showed no difference among treatments (P>0.05), with an average of conceptions of 36.58%. It is concluded that IGF-1, gSH and their association did not cause changes in sperm motility, mitochondrial potential, plasma and acrosomal membrane integrity. IGF-1 increased oxidative stress, however, there was no difference in the gestation rate among the treatments.(AU)

Objetivou-se avaliar a taxa de concepção, as condições metabólicas e estrutural das células espermáticas bovinas criopreservadas, acrescidas de diluidores com fator de crescimento semelhante à insulina do tipo 1(IGF-1) e glutationa (GSH). Foram utilizados 12 ejaculados de touros da raça Nelore, submetidos aos tratamentos: controle, gSH (2mM/mL), IGF-1 (100ng/mL) e gSH (1mM/mL) + IGF-1 (50ng/mL). Após a criopreservação e descongelação, o sêmen passou pelos testes de termorresistência rápida (TTRr), integridade de membrana plasmática e acrossomal (PIAI), alto potencial mitocondrial (AP), estresse oxidativo e taxa de concepção. Utilizou-se o teste de Tukey para as análises estatísticas das variáveis paramétricas e o teste de Friedman para as não paramétricas, com significância de 5%. A percentagem de gestação foi comparada pelo teste do qui-quadrado. Não hove diferença estatística (P<0,05) entre os tratamentos para a variável TTRr. Já no estresse oxidativo avaliado com a sonda CellROX, observou-se que o IGF-1 apresentou maior quantidade de células reativas (P<0,05), 36,38± 24,10. A PIAI, o AP e a taxa de gestação não apresentaram diferença entre tratamentos (P>0,05), com média de concepções de 36,58%. Conclui-se que o IGF-1, a gSH e a sua associação não causaram mudanças na motilidade espermática, no potencial mitocondrial, na integridade da membrana plasmática e acrossomal. O IGF-1 aumentou o estresse oxidativo, porém sem diferença na taxa de gestação entre os tratamentos.(AU)

Animals , Male , Cattle , Semen Preservation/methods , Semen Preservation/veterinary , Insulin-Like Growth Factor I , Cryopreservation/veterinary , Glutathione , Antioxidants/therapeutic use
Chinese Medical Journal ; (24): 1897-1907, 2021.
Article in English | WPRIM | ID: wpr-887658


Oxidative stress is caused by the imbalance between the generation of free radicals/reactive oxygen species (ROS) and the antioxidant defense systems, which can activate various transcription factors and affect their transcriptional pathways. Oxidative stress plays an important role in the occurrence and development of leukemia and is closely related to the treatment and prognosis of leukemia. The standard chemotherapy strategies for the pre-treatment of leukemia have many drawbacks. Hence, the usage of antioxidants and oxidants in the treatment of leukemia is being explored and has been preliminarily applied. This article reviews the research progress of oxidative stress and leukemia. In addition, the application of antioxidants treatment in leukemia has been summarized.

Antioxidants/therapeutic use , Humans , Leukemia/drug therapy , Oxidative Stress , Reactive Oxygen Species
Rev. bras. ter. intensiva ; 32(1): 108-114, jan.-mar. 2020. tab, graf
Article in English, Portuguese | LILACS | ID: biblio-1138452


RESUMO Objetivo: Avaliar a efetividade da estratificação para identificar e escolher alvos para terapia antioxidante em um modelo de sepse letal em animais e pacientes que desenvolveram hipotensão prolongada. Métodos: Submeteu-se um grupo de ratos à sepse induzida por ligadura e punção do ceco. Os animais foram divididos em dois grupos: os com níveis plasmáticos altos e os com níveis plasmáticos baixos de interleucina-6. Após a estratificação, administrou-se aos animais N-acetilcisteína mais desferroxamina ou soro fisiológico a partir de 3 e 12 horas após a cirurgia. Em pacientes hipotensos, N-acetilcisteína mais desferroxamina ou placebo foram administrados dentro de 12 horas após o cumprimento dos critérios para inclusão. Resultados: O uso de N-acetilcisteína mais desferroxamina aumentou a sobrevivência no modelo com ligadura mais punção do ceco quando a administração ocorreu 3 e 12 horas após indução da sepse. Ao utilizar os níveis de interleucina-6 para separar os animais que receberam antioxidantes, o efeito protetor só foi observado nos animais que tinham níveis elevados de interleucina-6. O efeito antioxidante de N-acetilcisteína mais desferroxamina foi similar nos dois grupos, porém observou-se diminuição significante dos níveis plasmáticos de interleucina-6 no grupo que apresentava elevado nível de interleucina-6. Em comparação com pacientes tratados com antioxidantes no subgrupo que tinha baixos níveis plasmáticos de interleucina-6, aqueles que tinham níveis elevados de interleucina-6 tiveram menor incidência de lesão renal aguda, porém não foram diferentes em termos de severidade da lesão renal aguda ou da mortalidade na unidade de terapia intensiva. Conclusão: Direcionar a terapia antioxidante para um elevado fenótipo inflamatório selecionaria uma população responsiva.

ABSTRACT Objective: To examine the effectiveness of stratification to identify and target antioxidant therapy for animal models of lethal sepsis and in patients who develop sustained hypotension. Methods: Rats were subjected to sepsis induced by cecal ligation and puncture. Animals were divided into two groups: those with high and low plasma levels of interleukin-6. Following stratification, N-acetylcysteine plus deferoxamine or saline was administered to animals starting 3 and 12 hours after surgery. N-Acetylcysteine plus deferoxamine or placebo was administered within 12 hours of meeting the inclusion criteria in hypotensive patients. Results: N-Acetylcysteine plus deferoxamine increased survival in the cecal ligation and puncture model when administered 3 and 12 hours after sepsis induction. When dividing animals that received antioxidants using plasma interleukin-6 levels, the protective effect was observed only in those animals with high IL-6 levels. The antioxidant effect of N-acetylcysteine + deferoxamine was similar in the two groups, but a significant decrease in plasma interleukin-6 levels was observed in the high-interleukin-6-level group. Compared with patients treated with antioxidants in the low-interleukin-6 subgroup, those in the high-interleukin-6 subgroup had a lower incidence of acute kidney injury but were not different in terms of acute kidney injury severity or intensive care unit mortality. Conclusion: Targeting antioxidant therapy to a high inflammatory phenotype would select a responsive population.

Humans , Animals , Male , Adult , Middle Aged , Aged , Rats , Acetylcysteine/therapeutic use , Sepsis/drug therapy , Deferoxamine/therapeutic use , Antioxidants/therapeutic use , Prognosis , Retrospective Studies , Treatment Outcome , Rats, Wistar
Article in English | LILACS, BBO | ID: biblio-1101285


Abstract Objective: To investigate the expression of High Mobility Group Box 1 (HMGB1) and Heat Shock Protein-70 (HSP-70) during orthodontic tooth movement (OTM) after (-)- Epigallocatechin-3-Gallate (EGCG) in East Java Green Tea (Camelia Sinensis) Methanolic Extract (GTME) administration in vivo. Material and Methods: 28 Wistar rats (Rattus Novergicus) was used and divided into 4 groups accordingly: K- without EGCG and OTM; K+ with OTM, without EGCG for 14 days; T1with OTM for 14 days and EGCG for 7 days; treatment group 2 (T2) with OTM and EGCG for 14 days. OTM animal model was achieved through the installation of the OTM device by means of NiTi close coil spring with 10g force placed between the first incisor and first maxillary molars. The samples were terminated on Day 14. The pre-maxillary was isolated for the immunohistochemical examination. Analysis of Variance (ANOVA) then continued with Tukey Honest Significant Difference (HSD) (p<0.05) was performed to analyze the data. Results: The highest HMGB1 and HSP-70 expression were found in the K+ group pressure side, meanwhile the lowest HMGB1 and HSP-70 expression were found in K- group tension side in the alveolar bone. There was a significant decrease of HMGB1 and HSP-70 expression in T2 compared to T1 and K+ with significant between groups (p<0.05; p=0.0001). Conclusion: The decreased expression of HMGB1 and HSP-70 in alveolar bone of OTM wistar rats due to post administration of GTME that consisted EGCG.

Animals , Rats , Tooth Movement Techniques/instrumentation , Rats, Wistar , HMGB1 Protein , Heat-Shock Proteins , Antioxidants/therapeutic use , Tea , Bone and Bones , Immunohistochemistry , Analysis of Variance , Models, Animal , Incisor , Indonesia , Molar
Acta cir. bras ; 35(1): e202000103, 2020. tab, graf
Article in English | LILACS | ID: biblio-1088520


Abstract Purpose To investigate the protective effect of Ganoderma lucidum on testicular torsion/detorsion (T/D)-induced ischemia-reperfusion (I/R) injury. Methods Thirty male Wistar albino rats were randomly categorized into 3 groups: Group 1: sham, Group 2 ( T/D): 2,5 hours of ischemia and 7 days of reperfusion, Group 3 (T/D+ G. lucidum ): 2,5 hours of ischemia and 7 days of reperfusion and 7 days of 20 mg/kg via gastric gavage G. lucidum polysaccharides per day. Biochemical assays of Malondialdehyde (MDA), superoxide dismutase (SOD), Catalase (CAT), Glutathione (GSH) levels , histopathology and expression levels of VEGF and Bcl-2 with immunohistochemical methods were examined in testicular tissue. Results G. lucidum treatment was found to have prevented the T/D-induced I/R injury by decreasing MDA levels of the testis. SOD, CAT and GSH activities were decreased in group 2, while they were increased in group 3 (p<0.001) and significant improvement in the tube diameter was observed in group 3. Bcl-2-positive germinal cells were lowered in group 3 compared to the group 2. VEGF expression showed an increase in group 2, whereas it decreased in group 3. Conclusion The antioxidant G. lucidum is thought to induce angiogenesis by reducing the apoptotic effect in testicular torsion-detorsion.

Animals , Male , Rats , Spermatic Cord Torsion/complications , Testis/blood supply , Reperfusion Injury/prevention & control , Reishi/chemistry , Antioxidants/therapeutic use , Spermatic Cord Torsion/metabolism , Superoxide Dismutase/metabolism , Testis/drug effects , Testis/pathology , Reperfusion Injury/etiology , Catalase/metabolism , Random Allocation , Rats, Wistar , Vascular Endothelial Growth Factor A/metabolism , Drug Evaluation, Preclinical , Malondialdehyde/metabolism , Antioxidants/pharmacology
Braz. arch. biol. technol ; 63: e20200131, 2020. tab, graf
Article in English | LILACS | ID: biblio-1132247


Abstract Gallic acid (GA), as a strong antioxidant, was selected in this study to investigate its possible nephroprotective effects against gentamicin (GM)-induced nephrotoxicity. Twenty-four rats were separated into three groups (n=8): group 1 (control group) received saline (0.5 mL/day), group 2 (GM group) received GM (100 mg/kg/day), and group 3 (treated group) received GM (100 mg/kg/day) and GA (100mg/kg/day). All treatments were performed intraperitoneally for 12 days. After 12 days, the rats were euthanized, and kidneys were removed immediately. For serum preparation, blood samples were collected before killing. Kidney paraffin sections were prepared from one of the kidneys and stained by the periodic acid-Schiff process. GA significantly decreased GM-induced renal histopathological injuries, including tubular necrosis, tubular cast, and leucocyte infiltration compared with the GM group. Additionally, GA significantly improved proteinuria, serum levels of urea and creatinine, and serum activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) compared with nephrotoxic animals. Furthermore, GA caused a significant improvement in the levels of cholesterol (Chol), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and cardiac risk ratios 1 and 2 in comparison with nephrotoxic animals. GA administration was observed to significantly improve the levels of lipid peroxidation, nitric oxide (NO), and glutathione (GSH) compared with the GM group. Finally, the activities and gene expression levels of catalase (CAT) and glutathione peroxidase (GPX) significantly increased following GA administration compared with the GM group. Our results indicated that GA has potential protective effects against GM nephrotoxicity by reducing oxidative stress in rats.

Animals , Male , Rats , Gentamicins/adverse effects , Oxidative Stress/drug effects , Gallic Acid/therapeutic use , Kidney Diseases/drug therapy , Anti-Bacterial Agents/adverse effects , Antioxidants/therapeutic use , Biomarkers , Cholesterol , Rats, Wistar , Disease Models, Animal , Gallic Acid/chemistry , Kidney Diseases/chemically induced , Kidney Diseases/pathology , Lipoproteins, HDL , Lipoproteins, LDL
Int. j. morphol ; 37(4): 1422-1428, Dec. 2019. graf
Article in English | LILACS | ID: biblio-1040148


Paracetamol (also called acetaminophen, or APAP) overdose causes acute damage to the liver and kidneys in both humans and experimental animal models via the induction of the oxidative stress pathway. We sought to determine whether the combined antioxidants and anti-inflammatory compounds, resveratrol (RES) and quercetin (QUR) can protect against kidney injury induced by a toxic dose of APAP in a rat model of APAP-induced acute kidney injury. Rats were either received a single dose of APAP (2 g/kg) before being sacrificed after 24 hours or were pre-treated for 7 days with combined doses of RES (30 mg/kg) and QUR (50 mg/kg) before being given a single dose of APAP and then sacrificed 24 hours post APAP ingestion. Harvested kidney tissues were prepared for light microscopy staining, and tissue samples were assayed for (i) biomarkers of oxidative stress and antioxidant, malondialdehyde (MDA) and superoxide dismutase (SOD); and (ii) biomarkers of inflammation, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Hematoxylin and eosin (H&E) stained images showed that APAP overdose induced acute kidney injury as demonstrated by widening of glomeruli space (Bowman space), tubular dilatation, numerous cellular debris in the renal tubules with tubular epithelial degeneration, and vacuolization, which were effectively protected by RES+QUR except a partial protection of the glomeruli space was observed. In addition, APAP significantly (p<0.05) modulated tissue levels of MDA, SOD, TNF-α, and IL-6, which were protected by RES+QUR. Furthermore, a significant (p<0.0001) positive correlation was observed between glomeruli space and TNF-α, (r=0.8899), IL-6 (r=0.8986), and MDA (r=0.8552), whereas glomeruli space scoring versus SOD showed negative correlation (r= - 0.7870). We conclude that resveratrol plus quercetin substantially protects against APAP-induced acute kidney injury in rats, possibly via the augmentation of antioxidants and inhibition of oxidative stress and inflammation.

La sobredosis de paracetamol (también llamado acetaminofen o APAP) causa un daño agudo en el hígado y los riñones, tanto en humanos como en modelos animales experimentales, a través de la inducción de la vía del estrés oxidativo. Intentamos determinar si los antioxidantes y los compuestos antiinflamatorios combinados, el resveratrol (RES) y la quercetina (QUR) pueden proteger contra la lesión renal inducida por una dosis tóxica de APAP en un modelo de rata de lesión renal aguda inducida por APAP. Las ratas recibieron una dosis única de APAP (2 g / kg) antes de ser sacrificadas después de 24 horas o se trataron previamente durante 7 días con dosis combinadas de RES (30 mg / kg) y QUR (50 mg / kg), antes de ser tratadas, se administró una dosis única de APAP y luego fueron sacrificadas 24 horas después de la ingestión. Los tejidos renales recolectados se tiñeron con H-E y fueron observados a través de microscopía óptica. Las muestras de tejido se analizaron para (i) biomarcadores de estrés oxidativo y antioxidante, malondialdehído (MDA) y superóxido dismutasa (SOD); y (ii) biomarcadores de inflamación, factor de necrosis tumoral alfa (TNF-α) e interleucina-6 (IL-6). Las imágenes teñidas con H & E mostraron que la sobredosis de APAP indujo daño renal agudo como lo demuestra la ampliación del espacio glomerular, la dilatación tubular, numerosos desechos celulares en los túbulos renales con degeneración epitelial tubular y la vacuolización, que se protegieron eficazmente con RES + QUR Se observó una protección parcial del espacio glomerular. Además, APAP modificó significativamente (p <0.05) los niveles tisulares de MDA, SOD, TNF-α e IL-6, que estaban protegidos por RES + QUR. Además, se observó una correlación positiva significativa (p <0,0001) entre el espacio glomerular y el TNF-α, (r = 0,8899), IL-6 (r = 0,8986) y MDA (r = 0,8552), mientras que la puntuación del espacio glomerular versus SOD mostró correlación negativa (r = - 0,7870). Concluimos que el resveratrol más quercetina protege sustancialmente contra la lesión renal aguda inducida por APAP en ratas, posiblemente a través del aumento de antioxidantes y la inhibición del estrés oxidativo y la inflamación.

Animals , Rats , Quercetin/therapeutic use , Acute Kidney Injury/drug therapy , Resveratrol/therapeutic use , Acetaminophen/toxicity , Quercetin/pharmacology , Oxidative Stress/drug effects , Disease Models, Animal , Drug Therapy, Combination , Acute Kidney Injury/chemically induced , Resveratrol/pharmacology , Acetaminophen/antagonists & inhibitors , Anti-Inflammatory Agents/therapeutic use , Antioxidants/therapeutic use
Braz. j. otorhinolaryngol. (Impr.) ; 85(6): 766-773, Nov.-Dec. 2019. tab, graf
Article in English | LILACS | ID: biblio-1055506


Abstract Introduction: Ototoxicity refers to cellular damage or function impairment developing in the inner ear in association with any therapeutic agent or chemical substance, and still represents the principal side-effect restricting the use of cisplatin. Objective: The aim of this study was to perform a biochemical, functional and histopathological investigation of the potential protective effect of eugenol against cisplatin-induced ototoxicity. Methods: The study was performed with 24 female Sprague Dawley rats. Distortion product otoacoustic emissions tests were performed on all animals, which were randomized into four equal groups. A single intraperitoneal dose of 15 mg/kg cisplatin was administered to cisplatin group, while the eugenol group received 100 mg/kg eugenol intraperitoneal for five consecutive days. 100 mg/kg eugenol was administered to cisplatin + eugenol group for 5 days. On the third day, these rats were received a single dose of 15 mg/kg cisplatin. The control group was given 8 mL/kg/day intraperitoneal saline solution for five days. The distortion product otoacoustic emissions test was repeated 24 h after the final drug administration. All animals were sacrificed, and the cochleas were subsequently used for biochemical and histopathological examinations. Results: Cisplatin caused oxidative stress in the cochlea, impaired the cochlear structure and significantly reduced signal noise ratio levels. Administration of eugenol together with cisplatin reversed these effects and provided functional, biochemical and histopathological protection. Conclusion: The study findings represent the first indication in the literature that eugenol may protect against ototoxicity by raising levels of antioxidant enzymes and lowering those of oxidant parameters.

Resumo Introdução: A ototoxicidade refere-se ao dano celular ou comprometimento da função da orelha interna associado a qualquer agente terapêutico ou substância química e ainda representa o principal efeito colateral que restringe o uso da cisplatina. Objetivo: O objetivo deste estudo foi realizar uma investigação bioquímica, funcional e histopatológica do potencial efeito protetor do eugenol contra a ototoxicidade induzida pela cisplatina. Método: O estudo foi realizado com 24 ratos fêmeas Sprague Dawley. Testes de emissões otoacústicas por produto de distorção foram realizados em todos os animais, os quais foram randomizados em quatro grupos iguais. Uma única dose intraperitoneal de 15 mg/kg de cisplatina foi administrada ao grupo cisplatina, enquanto o grupo eugenol recebeu 100 mg/kg de eugenol intraperitoneal por cinco dias consecutivos. Foram administrados 100 mg/kg de eugenol ao grupo cisplatina + eugenol durante 5 dias. No terceiro dia, estes ratos receberam uma dose única de 15 mg/kg de cisplatina. O grupo controle recebeu 8 mL/kg/dia de solução salina intraperitoneal por cinco dias. O teste de emissões otoacústicas por produto de distorção foi repetido 24 horas após a administração final do medicamento. Todos os animais foram sacrificados e as cócleas foram posteriormente utilizadas para exames bioquímicos e histopatológicos. Resultados: A cisplatina causou estresse oxidativo na cóclea, prejudicou a estrutura coclear e reduziu significativamente os níveis da relação sinal/ruído. A administração de eugenol juntamente com a cisplatina reverteu esses efeitos e forneceu proteção funcional, bioquímica e histopatológica. Conclusão: Os achados do estudo representam a primeira indicação na literatura de que o eugenol pode proteger contra a ototoxicidade, eleva os níveis de enzimas antioxidantes e diminui os níveis dos parâmetros oxidantes.

Animals , Female , Rats , Eugenol/therapeutic use , Cisplatin/toxicity , Hearing Loss/prevention & control , Antineoplastic Agents/toxicity , Antioxidants/therapeutic use , Rats, Sprague-Dawley , Otoacoustic Emissions, Spontaneous/drug effects , Cochlea/drug effects , Cochlea/pathology , Disease Models, Animal , Hearing Loss/chemically induced
Arq. neuropsiquiatr ; 77(8): 579-589, Aug. 2019. tab, graf
Article in English | LILACS | ID: biblio-1019465


ABSTRACT In this review, we discuss the therapies used in the treatment of patients with Duchenne muscular dystrophy since the first description of the disease. A short description is given of the various theories based on disease pathogenesis, which give the substrates for the many therapeutic interventions. A brief review of the methods of evaluation used in therapeutic trials is made. Of all the treatments, the only drugs that are still considered able to modify the course of the disease are the corticosteroids (prednisone/prednisolone/deflazacort). Other drugs (coenzyme Q10 and creatine) have had a little effect in a few functions without adverse reactions. Idebenone seems to improve the respiratory function in the long term. The trials with mRNA transcription, through nonsense mutations or exon 51 skipping, show some beneficial results in a few functional tests, but they are limited to a small set of DMD patients.

RESUMO Nesta revisão são discutidas as terapêuticas empregadas no tratamento da distrofia muscular de Duchenne desde a descrição da doença. Apresentamos as diversas teorias que fundamentaram as intervenções terapêuticas, com uma breve descrição dos tipos de avaliação empregados nos ensaios terapêuticos. Dentre todos os tratamentos, a única medicação que até agora modificou o curso da doença foram os corticosteroides (prednisona/prednisolona/deflazacort). A coenzima Q10 e creatina tiveram algum efeito pequeno em algumas funções e evolução da doença sem efeitos colaterais. O idebenone mostrou efeito benéfico na função respiratória em longo prazo. As tentativas de intervir no gene da distrofina utilizando técnicas de transcrição do mRNA através das mutações sem sentido e técnicas que pulam o exon 51 mostram resultado muito discreto em algumas provas funcionais e limitado a uma parcela pequena de casos.

Humans , Muscular Dystrophy, Duchenne/drug therapy , Calcium Channel Blockers/therapeutic use , Cholinesterase Inhibitors/therapeutic use , Dystrophin/drug effects , Dystrophin/metabolism , Adrenal Cortex Hormones/therapeutic use , Muscular Dystrophy, Duchenne/metabolism , Anti-Inflammatory Agents/therapeutic use , Antioxidants/therapeutic use
Rev. cuba. obstet. ginecol ; 45(2): e290, abr.-jun. 2019. tab
Article in Spanish | LILACS, CUMED | ID: biblio-1093644


Los suplementos dietarios tales como vitaminas, minerales y antioxidantes mejoran la ingesta de nutrientes. Recientemente se ha descrito que, especialmente aquellos que contienen altas propiedades antioxidantes también mejoran la capacidad fértil. Se presenta el caso de un voluntario de 37 años con posible infertilidad masculina y se desea determinar el efecto del consumo de antioxidantes sobre la calidad seminal. Se realizó evaluación de los parámetros seminales convencionales y funcionales antes y después del uso del suplemento dietario Male Fertility. Se observó que el uso del suplemento dietario incrementó la concentración espermática, el potencial de membrana mitocondrial alto y la capacidad antioxidante del semen; además disminuyó la producción de 1as reactivas de oxígeno, la lipoperoxidación y la fragmentación de la cromática espermática. El suplemento dietario Male Fertility contiene altas concentraciones de vitamina A, C, E, B2, B3, B12, folato, zinc, selenio, acetil L-carnitina, coenzima Q10, L-metionina y licopeno. Se ha descrito que la ingesta de cada uno de estos compuestos tiene efectos positivos sobre la calidad seminal. El reporte de este caso permitió observar que el uso de suplementos dietarios ricos en vitaminas y antioxidantes puede mejorar la calidad seminal a través de la disminución del efecto adverso de las especies reactivas del oxígeno y por el incremento de las moléculas antioxidantes en el plasma seminal(AU)

Dietary supplements such as vitamins, minerals and antioxidants improve nutrient intake. Recently it has been described that, especially those containing high antioxidant properties also improve fertility. We report here the case of a 37-year-old volunteer with possible male infertility and we want to determine the effect of antioxidant consumption on semen quality. Evaluation of the conventional and functional seminal parameters was performed before and after the use of the Male Fertility dietary supplement. The use of this supplement was observed to increased the sperm concentration, the mitochondrial membrane potential and the antioxidant capacity of the semen. In addition, the production of oxygen reactants, lipoperoxidation and fragmentation of the spermatic chromatin decreased. The dietary supplement Male Fertility contains high concentrations of vitamin A, C, E, B2, B3, B12, folate, zinc, selenium, acetyl L-carnitine, coenzyme Q10, L-methionine and lycopene. The ingestion of each of these compounds has been described to have positive effects on seminal quality. The report of this case allowed to observe that the use of dietary supplements rich in vitamins and antioxidants can improve the seminal quality through the decrease of the adverse effect of the reactive oxygen species and by the increase of the antioxidant molecules in the seminal plasma(AU)

Humans , Male , Adult , Semen Analysis/methods , Infertility, Male/therapy , Antioxidants/therapeutic use
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; 41(3): 245-253, May-June 2019. tab
Article in English | LILACS | ID: biblio-1011490


Objective: Bipolar depression is characterized by neurobiological features including perturbed oxidative biology, reduction in antioxidant levels, and a concomitant rise in oxidative stress markers. Bipolar depression manifests systemic inflammation, mitochondrial dysfunction, and changes in brain growth factors. The depressive phase of the disorder is the most common and responds the least to conventional treatments. Garcinia mangostana Linn, commonly known as mangosteen, is a tropical fruit. The pericarp's properties may reduce oxidative stress and inflammation and improve neurogenesis, making mangosteen pericarp a promising add-on therapy for bipolar depression. Methods: Participants will receive 24 weeks of either 1,000 mg mangosteen pericarp or placebo per day, in addition to their usual treatment. The primary outcome is change in severity of mood symptoms, measured using the Montgomery-Åsberg Depression Rating Scale (MADRS), over the treatment phase. Secondary outcomes include global psychopathology, quality of life, functioning, substance use, cognition, safety, biological data, and cost-effectiveness. A follow-up interview will be conducted 4 weeks post-treatment. Conclusion: The findings of this study may have implications for improving treatment outcomes for those with bipolar disorder and may contribute to our understanding of the pathophysiology of bipolar depression. Clinical trial registration: Australian and New Zealand Clinical Trial Registry, ACTRN12616000028404.

Humans , Bipolar Disorder/drug therapy , Garcinia mangostana/chemistry , Depressive Disorder/drug therapy , Fruit/chemistry , Antioxidants/therapeutic use , Placebos/therapeutic use , Quality of Life , Australia
Rev. habanera cienc. méd ; 18(2): 194-216, mar.-abr. 2019. tab, graf
Article in Spanish | LILACS, CUMED | ID: biblio-1014163


Introducción: En la actualidad se ha incrementado el uso de antioxidantes en el ámbito deportivo, sin embargo, no existe evidencia concluyente del efecto de estas sustancias en la mejora del desempeño físico de los atletas. Objetivo: Determinar la efectividad del uso de suplementos antioxidantes en la mejoría del desempeño físico atlético. Material y Métodos: Se realizó una revisión bibliográfica en bases de datos en línea como Pubmed, Scopus, la Web of Knowledge y el buscador google academic. Se incluyeron solo trabajos originales de estudios doble ciego relacionados con la intervención de un suplemento antioxidante. El periodo de revisión fue del 2009 a diciembre del 2017. Desarrollo: Se identificaron un total de 1053 artículos de los cuales 33 cumplieron con los criterios de inclusión de la revisión. De acuerdo con el tipo de suplemento, 2 correspondieron a vitaminas, 9 a polifenoles, 11 comerciales y los 9 restantes diversos. La antigüedad de los artículos analizados fue de 4,8 ± 2,4 años, en cuanto a la obsolescencia, determinado por el semiperiodo de Burton y Kleber y el índice de Price, fue 5,5 y 61,0 por ciento respectivamente. Conclusiones: Hasta el momento no existe evidencia sólida de que la ingesta de suplementos antioxidantes mejore el desempeño físico atlético. Son pocos los resultados positivos en alguna de las variables evaluadas, por tal motivo se requiere de mayor evidencia para poder dilucidar el efecto de los suplementos antioxidantes(AU)

Introduction: At present, the use of antioxidants in the sports field has increased. However, there is no conclusive evidence of the effect of these substances in improving the physical performance of athletes. Objective: To determine the effectiveness of antioxidant supplements in the improvement of athletic physical performance. Material and Methods: A bibliographic review was carried out through the search on online databases such as Pubmed, Scopus, the Web of Knowledge and Google Scholar search engine. Only original double-blind studies related to the intervention of an antioxidant supplement were included. The review period was from 2009 to December 2017. Development: A total of 1053 articles were identified, of which 33 met the inclusion criteria for the review. Regarding the type of supplement, 2 of them corresponded to vitamins, 9 to polyphenols, 11 to commercials, and the remaining 9 ones to several types. The historic period of the articles analyzed was 4.8 ± 2.4 years in terms of obsolescence, which was determined by the Burton and Kleber half-period and the Price index (5.5 and 61.0 percent respectively). Conclusions: To date, there is no solid evidence that the intake of antioxidant supplements improves physical athletic performance. There are few positive results in some of the evaluated variables; for this reason, more evidence is required to elucidate the effect of antioxidant supplements(AU)

Humans , Male , Female , Sports/standards , Antioxidants/therapeutic use
Braz. j. otorhinolaryngol. (Impr.) ; 85(1): 55-62, Jan.-Feb. 2019. tab, graf
Article in English | LILACS | ID: biblio-984047


Abstract Introduction: Cisplatin is one of the main chemotherapeutic agents used for the treatment of many types of cancer. However, ototoxicity, one of the most serious side effects of cisplatin, restricts its usage. Objective: We aimed to investigate the protective effects of whortleberry extract against cisplatin-induced ototoxicity by evaluating hearing and histopathological cochlear damage and by measuring the biochemical parameters affected byoxidative stress. Methods: Forty-eight male rats were included in the study after performing Distortion Product Otoacoustic Emission test to confirm that their hearing levels were normal. The rats were randomly divided into six groups: the control group, the sham group, and, which received only whortleberry extract, only cisplatin, cisplatin + 100 mg whortleberry extract, cisplatin + 200 mg whortleberry extract, respectively. Audiologic investigation was performed by performing the Distortion Product Otoacoustic Emission test at the beginning and at the eighth day of the study. Cardiac blood samples were collected for biochemical analysis, and the rats were sacrificed to obtain cochlear histopathological specimens on the eighth day. Results: The results revealed that whortleberry protects hearing against cisplatin-induced ototoxicity independent of the dose. However, high doses of whortleberry extract are needed to prevent histopathological degeneration and oxidative stress. Conclusion: The results obtained in this study show that whortleberry extract has a protective effect against cisplatin-induced ototoxicity.

Resumo Introdução: A cisplatina é um dos principais agentes quimioterápicos utilizados para o tratamento de muitos tipos de câncer. No entanto, a ototoxicidade, um dos efeitos colaterais mais graves da cisplatina, restringe seu uso. Objetivo: Nosso objetivo foi investigar os efeitos protetores do extrato de uva-do-monte contra a ototoxicidade induzida por cisplatina, avaliar o dano auditivo e histopatológico coclear e medir os parâmetros bioquímicos afetados pelo estresse oxidativo. Método: Foram incluídos no estudo 48 ratos machos após teste de emissão otoacústica evocada por produto de distorção para confirmar que seus níveis de audição eram normais. Os ratos foram divididos aleatoriamente em seis grupos: o grupo controle, o grupo simulado, o que recebeu apenas extrato de uva-do-monte, o que recebeu apenas cisplatina, o que recebeu cisplatina + 100 mg de extrato de uva-do-monte e o que recebeu cisplatina + 200 mg de extrato de uva-do-monte, respectivamente. A investigação audiológica foi feita através do teste de emissão otoacústica de produto de distorção no início e no oitavo dia do estudo. As amostras de sangue cardíaco foram coletadas para análise bioquímica e os ratos foram sacrificados para obtenção de espécimes histopatológicos cocleares no oitavo dia. Resultados: Os resultados revelaram que o extrato de uva-do-monte protege a audição contra a ototoxicidade induzida por cisplatina, independentemente da dose. No entanto, são necessárias doses elevadas do extrato para evitar a degeneração histopatológica e o estresse oxidativo. Conclusão: Os resultados obtidos neste estudo mostram que o extrato de uva-do-monte tem um efeito protetor contra a ototoxicidade induzida por cisplatina.

Animals , Male , Cisplatin/toxicity , Cochlea/drug effects , Protective Agents/therapeutic use , Hearing/drug effects , Anthocyanins/therapeutic use , Antineoplastic Agents/toxicity , Reference Values , Acoustic Stimulation , Random Allocation , Reproducibility of Results , Treatment Outcome , Rats, Wistar , Otoacoustic Emissions, Spontaneous/drug effects , Cochlea/pathology , Oxidative Stress/drug effects , Antioxidants/therapeutic use
Acta cir. bras ; 34(9): e201900904, 2019. tab, graf
Article in English | LILACS | ID: biblio-1054694


Abstract Purpose: Ganoderma lucidum, a kind of mushroom used for its antioxidant, anti-inflammatory, and immunomodulatory activities, was investigated in the present study for its possible healing effect on calvarial defects with bone grafts. Methods: Wistar male rats (n = 30) were divided into 3 groups: 1) the control (defect) group (n = 10), 2) defect and graft group (n = 10), and 3) defect, graft, and G. lucidum treated group (n = 10). The G. lucidum was administered to the rats at 20 mL/kg per day via gastric lavage. Results: In the defect and graft group, osteonectin positive expression was observed in osteoblast and osteocyte cells at the periphery of the small bone trabeculae within the graft area. In the defect, graft, and G. lucidum treated group, osteonectin expression was positive in the osteoblast and osteocyte cells and positive osteonectin expression in new bone trabeculae. The expression of matrix metalloproteinase-9 (MMP-9) was positive in the inflammatory cells, fibroblast cells, and degenerated collagen fibril areas within the defect area. Conclusion: This study shows that, with its antioxidant and anti-inflammatory properties, G. Lucidum is an important factor in the treatment of calvarial bone defects.

Animals , Male , Rats , Skull/surgery , Bone Regeneration/drug effects , Bone Transplantation , Reishi/chemistry , Anti-Inflammatory Agents/therapeutic use , Antioxidants/therapeutic use , Skull/drug effects , Immunohistochemistry , Osseointegration/drug effects , Rats, Wistar , Disease Models, Animal
J. appl. oral sci ; 27: e20180211, 2019. tab, graf
Article in English | LILACS, BBO | ID: biblio-984568


Abstract Objective The aim of this study was to evaluate the effects of gliclazide on oxidative stress, inflammation, and bone loss in an experimental periodontal disease model. Material and Methods Male albino Wistar rats were divided into no ligature, ligature, and ligature with 1, 5, and 10 mg/kg gliclazide groups. Maxillae were fixed and scanned using micro-computed tomography to quantify linear and bone volume/tissue volume (BV/TV) and volumetric bone loss. Histopathological, immunohistochemical and immunofluorescence analyses were conducted to examine matrix metalloproteinase-2 (MMP-2), cyclooxygenase 2 (COX-2), cathepsin K, members of the receptor activator of the nuclear factor kappa-Β ligand (RANKL), receptor activator of nuclear factor kappa-Β (RANK), osteoprotegerin (OPG) pathway, macrophage migration inhibitory factor (MIF), superoxide dismutase-1 (SOD-1), glutathione peroxidase-1 (GPx-1), NFKB p 50 (Cytoplasm), NFKB p50 NLS (nuclear localization signal), PI3 kinase and AKT staining. Myeloperoxidase activity, malondialdehyde and glutathione levels, while interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) levels were evaluated by spectroscopic ultraviolet-visible analysis. A quantitative reverse transcription polymerase chain reaction was used to quantify the gene expression of the nuclear factor kappa B p50 subunit (NF-κB p50), phosphoinositide 3-kinase (PI3k), protein kinase B (AKT), and F4/80. Results Micro-computed tomography showed that the 1 mg/kg gliclazide treatment reduced linear bone loss compared to the ligature, 5 mg/kg gliclazide, and 10 mg/kg gliclazide treatments. All concentrations of gliclazide increased bone volume/tissue volume (BV/TV) compared to the ligature group. Treatment with 1 mg/kg gliclazide reduced myeloperoxidase activity, malondialdehyde, IL-1β, and TNF-α levels (p≤0.05), and resulted in weak staining for COX-2, cathepsin k, MMP-2, RANK, RANKL, SOD-1, GPx-1,MIF and PI3k. In addition, down-regulation of NF-κB p50, PI3k, AKT, and F4/80 were observed, and OPG staining was strong after the 1 mg/kg gliclazide treatment. Conclusions This treatment decreased neutrophil and macrophage migration, decreased the inflammatory response, and decreased bone loss in rats with ligature-induced periodontitis.

Animals , Male , Periodontitis/drug therapy , Alveolar Bone Loss/drug therapy , Oxidative Stress/drug effects , Gliclazide/pharmacology , Antioxidants/pharmacology , Periodontitis/pathology , Immunohistochemistry , Random Allocation , Reproducibility of Results , Alveolar Bone Loss/pathology , Fluorescent Antibody Technique , Macrophage Migration-Inhibitory Factors/adverse effects , Tumor Necrosis Factor-alpha/analysis , Rats, Wistar , Peroxidase/analysis , Reverse Transcriptase Polymerase Chain Reaction , Matrix Metalloproteinase 2/analysis , Interleukin-1beta/analysis , RANK Ligand/analysis , Receptor Activator of Nuclear Factor-kappa B/analysis , X-Ray Microtomography , Cathepsin K/analysis , Gingiva/pathology , Gingiva/chemistry , Gliclazide/therapeutic use , Glutathione/analysis , Malondialdehyde/analysis , Neutrophils/drug effects , Antioxidants/therapeutic use