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Int. arch. otorhinolaryngol. (Impr.) ; 24(1): 47-52, Jan.-Mar. 2020. graf
Article in English | LILACS | ID: biblio-1090559


Abstract Introduction Cisplatin damages the auditory system and is related to the generation of free radicals. Glutathione peroxidase is an endogenous free radicals remover. Objective To investigate the mechanisms involved in otoprotection by N-acetylcys- teine through the expression of glutathione peroxidase in outer hair cells from rats treated with cisplatin. Methods Male Wistar rats were intraperitoneally injected with cisplatin (8 mg/Kg) and/or received oral administration by gavage of N-acetylcysteine (300 mg/Kg) for 3 consecutive days. On the 4th day, the animals were euthanized and beheaded. The tympanic bullae were removed and prepared for scanning electron microscopy and Results Among the groups exposed to ototoxic doses of cisplatin, there was an increase in glutathione peroxidase immunostaining in two groups, the one exposed to cisplatin alone, and the group exposed to both cisplatin and N-acetylcysteine. Conclusion The expression of glutathione peroxidase in the outer hair cells of rats exposed to cisplatin showed the synthesis of this enzyme under cellular toxicity conditions.

Animals , Male , Acetylcysteine/therapeutic use , Free Radical Scavengers/therapeutic use , Cisplatin/toxicity , Oxidative Stress/drug effects , Antineoplastic Agents/toxicity , Acetylcysteine/metabolism , Acetylcysteine/pharmacology , Microscopy, Electron, Scanning , Evoked Potentials, Auditory, Brain Stem , Free Radical Scavengers/metabolism , Free Radical Scavengers/pharmacology , Fluorescent Antibody Technique , Cisplatin/therapeutic use , Rats, Wistar , Cochlea/anatomy & histology , Cochlea/drug effects , Free Radicals , Glutathione Peroxidase/metabolism , Hearing Loss, Sensorineural/prevention & control
Einstein (Säo Paulo) ; 18: eAO5022, 2020. graf
Article in English | LILACS | ID: biblio-1090060


ABSTRACT Objective To evaluate the effects of oxidative stress on insulin signaling in cardiac tissue of obese mice. Methods Thirty Swiss mice were equally divided (n=10) into three groups: Control Group, Obese Group, and Obese Group Treated with N-acetylcysteine. After obesity and insulin resistance were established, the obese mice were treated with N-acetylcysteine at a dose of 50mg/kg daily for 15 days via oral gavage. Results Higher blood glucose levels and nitrite and carbonyl contents, and lower protein levels of glutathione peroxidase and phosphorylated protein kinase B were observed in the obese group when compared with their respective control. On the other hand, treatment with N-acetylcysteine was effective in reducing blood glucose levels and nitrite and carbonyl contents, and significantly increased protein levels of glutathione peroxidase and phosphorylated protein kinase B compared to the Obese Group. Conclusion Obesity and/or a high-lipid diet may result in oxidative stress and insulin resistance in the heart tissue of obese mice, and the use of N-acetylcysteine as a methodological and therapeutic strategy suggested there is a relation between them.

RESUMO Objetivo Avaliar os efeitos do estresse oxidativo sobre a sinalização da insulina em tecido cardíaco de camundongos obesos. Métodos Utilizaram-se 30 camundongos Swiss subdivididos igualmente (n=10) em três grupos: Grupo Controle, Grupo Obeso e Grupo Obeso Tratado com N-acetilcisteína. Após estabelecidas a obesidade e a resistência à insulina, os camundongos obesos foram tratados diariamente, durante 15 dias, via gavagem oral, com N-acetilcisteína na dose de 50mg/kg. Resultados Observaram-se maiores níveis de glicose sanguínea, conteúdos de nitrito e carbonil, e menores níveis proteicos de glutationa peroxidase e proteína quinase B fosforilada no Grupo Obeso quando comparado a seu respectivo controle. Por outro lado, o tratamento com N-acetilcisteína se mostrou eficiente em diminuir os níveis glicêmicos, os conteúdos de nitrito e carbonil, e aumentar significativamente os níveis proteicos de glutationa peroxidase e proteína quinase B fosforilada, quando comparados ao Grupo Obeso. Conclusão Obesidade e/ou dieta hiperlipídica levam a estresse oxidativo e à resistência à insulina no tecido cardíaco de camundongos obesos, e o uso da N-acetilcisteína como estratégia metodológica e terapêutica sugeriu haver relação entre ambos.

Humans , Animals , Male , Mice , Acetylcysteine/pharmacology , Insulin Resistance/physiology , Free Radical Scavengers/pharmacology , Oxidative Stress/physiology , Diet, High-Fat , Myocardium/metabolism , Reference Values , Spectrophotometry , Blood Glucose/analysis , Body Weight , Blotting, Western , Reactive Oxygen Species/analysis , Oxidative Stress/drug effects , Protein Carbonylation , Fluoresceins/analysis
Biol. Res ; 53: 28, 2020. graf
Article in English | LILACS | ID: biblio-1124213


BACKGROUND: Kidney ischemia-reperfusion injury is a common pathophysiological phenomenon in the clinic. A large number of studies have found that the tyrosine protein kinase/signal transducer and activator of transcription (JAK/STAT) pathway is involved in the development of a variety of kidney diseases and renal protection associated with multiple drugs. Edaravone (EDA) is an effective free radical scavenger that has been used clinically for the treatment of postischemic neuronal injury. This study aimed to identify whether EDA improved kidney function in rats with ischemia-reperfusion injury by regulating the JAK/STAT pathway and clarify the underlying mechanism. METHODS: Histomorphological analysis was used to assess pathological kidney injury, and mitochondrial damage was observed by transmission electron microscopy. Terminal deoxynucleotidyl transferase-mediated dUTP nick endlabeling (TUNEL) staining was performed to detect tubular epithelial cell apoptosis. The expression of JAK2, P-JAK2, STAT3, P-STAT3, STAT1, P-STAT1, BAX and Bcl-2 was assessed by western blotting. Mitochondrial function in the kidney was assessed by mitochondrial membrane potential (ΔψM) measurement. RESULTS: The results showed that EDA inhibited the expression of p-JAK2, p-STAT3 and p-STAT1, accompanied by downregulation of the expression of Bax and caspase-3, and significantly ameliorated kidney damage caused by ischemia-reperfusion injury (IRI). Furthermore, the JC-1 dye assay showed that edaravone attenuated ischemia-reperfusion-induced loss of kidney (ΔψM). CONCLUSION: Our findings indicate that EDA protects against kidney damage caused by ischemia-reperfusion through JAK/STAT signaling, inhibiting apoptosis and improving mitochondrial injury.

Animals , Male , Rats , Reperfusion Injury/drug therapy , Free Radical Scavengers/pharmacology , Edaravone/pharmacology , Signal Transduction/drug effects , Rats, Sprague-Dawley , Apoptosis , STAT Transcription Factors/drug effects , Janus Kinases/drug effects , Mitochondria
An. acad. bras. ciênc ; 89(1,supl): 577-589, May. 2017. tab, graf
Article in English | LILACS | ID: biblio-886660


ABSTRACT Peel extracts of litchi and rambutan, and that of tamarind seed coat were investigated in relation to their utility in skin-aging treatments. Standardized extracts of tamarind were significantly (p < 0.05) more efficient at O2 •- scavenging (IC50 = 27.44 ± 0.09) than those of litchi and rambutan (IC50 = 29.57 ± 0.30 and 39.49 ± 0.52 μg/ml, respectively) and the quercetin standard (IC50 = 31.88 ± 0.15 μg/ml). Litchi extract proved significantly (p < 0.05) more effective for elastase and collagenase inhibition (88.29 ± 0.25% and 79.46 ± 0.92%, respectively) than tamarind (35.43 ± 0.68% and 57.69 ± 5.97%) or rambutan (31.08 ± 0.38% and 53.99 ± 6.18%). All extracts were safe to human skin fibroblasts and inhibit MMP-2, with litchi extract showing significantly (p < 0.01) enhanced inhibition over the standard, vitamin C (23.75 ± 2.74% and 10.42 ± 5.91% at 0.05 mg/ml, respectively). Extracts suppress melanin production in B16F10 melanoma cells through inhibition of tyrosinase and TRP-2, with litchi extract being the most potent, even more so than kojic acid (standard). These results highlight the potential for adding value to agro-industrial waste, as the basis for the sustainable production of innovative, safe, anti-aging cosmetic products.

Humans , Plant Extracts/pharmacology , Skin Aging/drug effects , Tamarindus/chemistry , Sapindaceae/chemistry , Litchi/chemistry , Antioxidants/pharmacology , Phenols/pharmacology , Administration, Cutaneous , Free Radical Scavengers/pharmacology , Cosmetics , Fibroblasts/drug effects , Fruit/chemistry , Antioxidants/isolation & purification
Mem. Inst. Oswaldo Cruz ; 112(2): 146-154, Feb. 2017. graf
Article in English | LILACS | ID: biblio-841766


BACKGROUND Leishmaniasis is a parasitosis caused by several species of the genus Leishmania. These parasites present high resistance against oxidative stress generated by inflammatory cells. OBJECTIVES To investigate oxidative stress and molecular inflammatory markers in BALB/c mice infected with L. amazonensis and the effect of antioxidant treatment on these parameters. METHODS Four months after infection, oxidative and inflammatory parameters of liver, kidneys, spleen, heart and lungs from BALB/c mice were assessed. FINDINGS In liver, L. amazonensis caused thiol oxidation and nitrotyrosine formation; SOD activity and SOD2 protein content were increased while SOD1 protein content decreased. The content of the cytokines IL-1β, IL-6, TNF-α, and the receptor of advanced glycation endproducts (RAGE) increased in liver. Treatment with the antioxidant N-acetyl-cysteine (20 mg/kg b.w) for five days inhibited oxidative stress parameters. MAIN CONCLUSIONS L. amazonensis induces significant alterations in the redox status of liver but not in other organs. Acute antioxidant treatment alleviates oxidative stress in liver, but it had no effect on pro-inflammatory markers. These results indicate that the pathobiology of leishmaniasis is not restricted to the cutaneous manifestations and open perspectives for the development of new therapeutic approaches to the disease, especially for liver function.

Animals , Mice , Acetylcysteine/pharmacology , Leishmania mexicana , Leishmaniasis, Cutaneous/metabolism , Leishmaniasis, Cutaneous/pathology , Oxidative Stress/drug effects , Oxidative Stress/physiology , Free Radical Scavengers/pharmacology , Liver/drug effects , Liver/enzymology , Mice, Inbred BALB C
Braz. j. med. biol. res ; 50(12): e6087, 2017. graf
Article in English | LILACS | ID: biblio-888963


Using an iron overload mouse model, we explored the protective effect of deferasirox (DFX) and N-acetyl-L-cysteine (NAC) on injured bone marrow hematopoietic stem/progenitor cells (HSPC) induced by iron overload. Mice were intraperitoneally injected with 25 mg iron dextran every 3 days for 4 weeks to establish an iron overload (Fe) model. DFX or NAC were co-administered with iron dextran in two groups of mice (Fe+DFX and Fe+NAC), and the function of HSPCs was then examined. Iron overload markedly decreased the number of murine HSPCs in bone marrow. Subsequent colony-forming cell assays showed that iron overload also decreased the colony forming capacity of HSPCs, the effect of which could be reversed by DFX and NAC. The bone marrow hematopoiesis damage caused by iron overload could be alleviated by DFX and NAC.

Animals , Male , Acetylcysteine/pharmacology , Triazoles/pharmacology , Benzoates/pharmacology , Hematopoietic Stem Cells/drug effects , Iron Chelating Agents/pharmacology , Free Radical Scavengers/pharmacology , Iron Overload/prevention & control , Protective Agents/pharmacology , Reference Values , Time Factors , Reproducibility of Results , Treatment Outcome , Reactive Oxygen Species/analysis , Colony-Forming Units Assay , Disease Models, Animal , Flow Cytometry , Hematopoiesis/drug effects , Mice, Inbred C57BL
Braz. j. med. biol. res ; 50(12): e6533, 2017. graf
Article in English | LILACS | ID: biblio-888965


N-acetylcysteine (NAC) inhibits nociceptive transmission. This effect has been associated partly with its antioxidant properties. However, the effect of NAC on the levels of lipid hydroperoxides (a pro-oxidant marker), content of ascorbic acid (a key antioxidant molecule of nervous tissue) and total antioxidant capacity (TAC) is unknown. Thus, our study assessed these parameters in the lumbosacral spinal cord of rats with chronic constriction injury (CCI) of the sciatic nerve, one of the most commonly employed animal models of neuropathic pain. Thirty-six male Wistar rats weighing 200-300 g were equally divided into the following groups: Naive (rats did not undergo surgical manipulation); Sham (rats in which all surgical procedures involved in CCI were used except the ligature), and CCI (rats in which four ligatures were tied loosely around the right common sciatic nerve). All rats received intraperitoneal injections of NAC (150 mg·kg−1·day−1) or saline for 1, 3, or 7 days. Rats were killed 1, 3, and 7 days after surgery. NAC treatment prevented the CCI-induced increase in lipid hydroperoxide levels only at day 1, although the amount was higher than that found in naive rats. NAC treatment also prevented the CCI-induced increase in ascorbic acid content, which occurred at days 1, 3, and 7. No significant change was found in TAC with NAC treatment. The changes observed here may be related to the antinociceptive effect of NAC because modulation of oxidative-stress parameters seemed to help normalize the spinal cord oxidative status altered by pain.

Animals , Male , Acetylcysteine/pharmacology , Free Radical Scavengers/pharmacology , Neuralgia/drug therapy , Neuralgia/metabolism , Oxidative Stress/drug effects , Spinal Cord/drug effects , Spinal Cord/metabolism , Antioxidants , Ascorbic Acid/analysis , Biomarkers/analysis , Constriction , Lipid Peroxides/analysis , Rats, Wistar , Reactive Oxygen Species/metabolism , Reproducibility of Results , Sciatic Neuropathy , Time Factors , Treatment Outcome
J. bras. pneumol ; 42(1): 9-14, Jan.-Feb. 2016. graf
Article in Portuguese | LILACS | ID: lil-776473


Objective : To investigate the effects of N-acetylcysteine (NAC) and pentoxifylline in a model of remote organ injury after hind-limb ischemia/reperfusion (I/R) in rats, the lungs being the remote organ system. Methods : Thirty-five male Wistar rats were assigned to one of five conditions (n = 7/group), as follows: sham operation (control group); hind-limb ischemia, induced by clamping the left femoral artery, for 2 h, followed by 24 h of reperfusion (I/R group); and hind-limb ischemia, as above, followed by intraperitoneal injection (prior to reperfusion) of 150 mg/kg of NAC (I/R+NAC group), 40 mg/kg of pentoxifylline (I/R+PTX group), or both (I/R+NAC+PTX group). At the end of the trial, lung tissues were removed for histological analysis and assessment of oxidative stress. Results : In comparison with the rats in the other groups, those in the I/R group showed lower superoxide dismutase activity and glutathione levels, together with higher malondialdehyde levels and lung injury scores (p < 0.05 for all). Interstitial inflammatory cell infiltration of the lungs was also markedly greater in the I/R group than in the other groups. In addition, I/R group rats showed various signs of interstitial edema and hemorrhage. In the I/R+NAC, I/R+PTX, and I/R+NAC+PTX groups, superoxide dismutase activity, glutathione levels, malondialdehyde levels, and lung injury scores were preserved (p < 0.05 for all). The differences between the administration of NAC or pentoxifylline alone and the administration of the two together were not significant for any of those parameters (p > 0.05 for all). Conclusions : Our results suggest that NAC and pentoxifylline both protect lung tissue from the effects of skeletal muscle I/R. However, their combined use does not appear to increase the level of that protection.

Objetivo : Investigar os efeitos da N-acetilcisteína (NAC) e pentoxifilina em um modelo de lesão pulmonar remota após isquemia/reperfusão (I/R) de membro posterior em ratos. Métodos : Trinta e cinco ratos Wistar machos foram divididos em cinco grupos (n = 7/grupo), cada qual submetido ao seguinte: operação simulada (grupo controle); isquemia de membro posterior, induzida por pinçamento da artéria femoral esquerda por 2 h, seguida por de 24 h de reperfusão (grupo I/R); e isquemia de membro posterior, como descrito acima, seguida de injeção intraperitoneal (antes da reperfusão) de 150 mg/kg de NAC (grupo I/R+NAC), 40 mg/kg de pentoxifilina (grupo I/R+PTX) ou ambas (grupo I/R+NAC+PTX). Ao final do experimento, tecidos pulmonares foram removidos para análise histológica e avaliação do estresse oxidativo. Resultados : Comparados aos ratos dos outros grupos, os do grupo I/R apresentaram menor atividade de superóxido dismutase e menores níveis de glutationa, além de maiores níveis de malondialdeído e maiores escores de lesão pulmonar (p < 0,05 para todos). Infiltração celular inflamatória intersticial dos pulmões também foi bem maior no grupo I/R do que nos outros grupos. Além disso, os ratos do grupo I/R apresentaram vários sinais de edema intersticial e hemorragia. Nos grupos I/R+NAC, I/R+PTX e I/R+NAC+PTX, a atividade de superóxido dismutase, níveis de glutationa, níveis de malondialdeído e escores de lesão pulmonar foram preservados (p < 0,05 para todos). As diferenças entre a administração de NAC ou pentoxifilina isoladamente e a das duas combinadas não foi significativa para nenhum desses parâmetros (p > 0,05 para todos). Conclusões : Nossos resultados sugerem que tanto NAC quanto pentoxifilina protegem o tecido pulmonar dos efeitos de I/R de músculo esquelético. Entretanto, seu uso combinado não parece aumentar o nível dessa proteção.

Animals , Male , Acetylcysteine/pharmacology , Free Radical Scavengers/pharmacology , Ischemia/prevention & control , Lung Injury/prevention & control , Lung/blood supply , Pentoxifylline/pharmacology , Reperfusion Injury/prevention & control , Acetylcysteine/therapeutic use , Disease Models, Animal , Free Radical Scavengers/therapeutic use , Glutathione/analysis , Hindlimb/blood supply , Lung Injury/pathology , Lung/drug effects , Lung/pathology , Malondialdehyde/analysis , Oxidative Stress , Pentoxifylline/therapeutic use , Random Allocation , Rats, Wistar , Reproducibility of Results , Superoxide Dismutase/analysis , Time Factors
Int. braz. j. urol ; 41(5): 935-944, Sept.-Oct. 2015. tab, graf
Article in English | LILACS | ID: lil-767061


ABSTRACT Purpose: For most cases, urolithiasis is a condition where excessive oxalate is present in the urine. Many reports have documented free radical generation followed by hyperoxaluria as a consequence of which calcium oxalate (CaOx) deposition occurs in the kidney tissue. The present study is aimed to exam the antilithiatic potency of the aqueous extract (AE) of Terminalia arjuna (T. arjuna). Materials and Methods: The antilithiatic activity of Terminalia arjuna was investigated in vitro nucleation, aggregation and growth of the CaOx crystals as well as the morphology of CaOx crystals using the inbuilt software ‘Image-Pro Plus 7.0’ of Olympus upright microscope (BX53). Antioxidant activity of AE of Terminalia arjuna bark was also determined in vitro. Results: Terminalia arjuna extract exhibited a concentration dependent inhibition of nucleation and aggregation of CaOx crystals. The AE of Terminalia arjuna bark also inhibited the growth of CaOx crystals. At the same time, the AE also modified the morphology of CaOx crystals from hexagonal to spherical shape with increasing concentrations of AE and reduced the dimensions such as area, perimeter, length and width of CaOx crystals in a dose dependent manner. Also, the Terminalia arjuna AE scavenged the DPPH (2, 2-diphenyl-1-picrylhydrazyl) radicals with an IC50 at 13.1µg/mL. Conclusions: The study suggests that Terminalia arjuna bark has the potential to scavenge DPPH radicals and inhibit CaOx crystallization in vitro. In the light of these studies, Terminalia arjuna can be regarded as a promising candidate from natural plant sources of antilithiatic and antioxidant activity with high value.

Antioxidants/pharmacology , Calcium Oxalate/chemistry , Plant Extracts/pharmacology , Terminalia/chemistry , Urinary Calculi/prevention & control , Analysis of Variance , Biphenyl Compounds/chemistry , Crystallization , Free Radical Scavengers/pharmacology , Phytotherapy , Picrates/chemistry , Reference Values , Reproducibility of Results , Urinary Calculi/chemistry
Int. braz. j. urol ; 41(3): 576-583, May-June 2015. tab, ilus
Article in English | LILACS | ID: lil-755872



The objective of the present study was to investigate the role of pentoxifylline (PTX) on remote testicular injury caused by unilateral hind limb ischemia/reperfusion of rats.

Materials and Methods

Twenty healthy male Wistar rats were allocated randomly into two groups: ischemia/reperfusion (IR group) and ischemia/reperfusion + pentoxifylline (IR+PTX group). Ischemia was induced by placement of a rubber tourniquet at the greater trochanter for 2h. Rats in IR+PTX group received PTX (40 mg/kg IP) before the reperfusion period. At 24h after reperfusion, testes were removed and levels of superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT) and myeloperoxidase (MPO) activity were determined in testicular tissues. Three rats of each group were used for wet/ dry weight ratio measurement. Testicular tissues were also examined histopathologically under light microscopy.


Activities of SOD and CAT in testicular tissues were decreased by ischemia/ reperfusion (P<0.05). Significantly increased MDA levels in testicular tissues were decreased by PTX treatment (P<0.05). MPO activity in testicular tissues in the IR group was significantly higher than in the IR+PTX group (P<0.05). The wet/dry weight ratio of testicular tissues in the IR group was significantly higher than in the IR+PTX group (P<0.05). Histopathologically, there was a statistically significant difference between two groups (P<0.05).


According to histological and biochemical findings, we conclude that PTX has preventive effects in the testicular injury induced by hind limb ischemia/reperfusion.


Animals , Male , Free Radical Scavengers/pharmacology , Hindlimb/blood supply , Pentoxifylline/pharmacology , Reperfusion Injury/prevention & control , Testis/drug effects , Catalase/analysis , Disease Models, Animal , Ischemia/complications , Ischemia/prevention & control , Malondialdehyde/analysis , Peroxidase/analysis , Random Allocation , Rats, Wistar , Reproducibility of Results , Reperfusion Injury/complications , Superoxide Dismutase/analysis , Time Factors , Treatment Outcome , Testis/chemistry , Testis/metabolism , Testis/pathology
Rev. bras. cir. cardiovasc ; 30(2): 173-181, Mar-Apr/2015. tab, graf
Article in English | LILACS | ID: lil-748938


Abstract Introduction: Pharmacological therapy is a strategy for the prevention of complications associated with ischemia and reperfusion injury that occurs after volume replacement in the treatment of hemorrhagic shock. Objective: The aim of this study was to evaluate the effect of N-acetylcysteine associated with fluid resuscitation in cardiac injury in a rat hemorrhagic shock model. Methods: Mice Wister male rats were randomly and subjected to controlled hemorrhagic shock for 60 min. and then, subjected to resuscitation with Ringer lactate. In a group of six animals, 150mg/kg of N-acetylcysteine were added to fluid volume replacement. The animals were observed for 120 min and after this period, were euthanized and cardiac tissue was collected for histopathological analysis and measurement of thiobarbituric acid reactive substances and pro-and anti-inflammatory interleukin. Results: Cardiac tissue of the group treated with N-acetylcysteine showed lower concentrations of thiobarbituric acid reactive substances (0.20±0.05 vs. 0.27±0.05, P=0.014) and reduced histopathological damage and edema when compared to the group whose volume replacement occurred only with Ringer lactate. There was no difference in the expression of cytokines interleukin 6 (2,138.29±316.89 vs. 1,870.16±303.68, P=0.091) and interleukin 10 (1.019,83±262,50 vs. 848.60±106.5, P=0.169) between the treated groups. Conclusion: The association of N-acetylcysteine on volume replacement attenuates oxidative stress in the heart, as well myocardial damage and edema, but does not modify the expression of inflammatory cytokines. .

Resumo Introdução: A terapia farmacológica é uma estratégia de prevenção das complicações associadas à lesão de isquemia e reperfusão tecidual que ocorre após a reposição volêmica no tratamento do choque hemorrágico. Objetivo: O objetivo deste estudo foi avaliar a repercussão da N-acetilcisteína associada à reposição volêmica na lesão cardíaca em modelo de choque hemorrágico em ratos. Métodos: Ratos Wistar, machos, foram randomizados e submetidos ao choque hemorrágico controlado por 60 minutos e, depois, submetidos à reposição volêmica com Ringer Lactato. Em um grupo de seis animais, foram adicionados 150 mg/Kg de N-acetilcisteína ao fluido de reposição volêmica. Os animais foram observados por 120 minutos e após este período foram submetidos à eutanásia e coleta do tecido cardíaco para análise histopatológica e dosagem de substâncias reativas ao ácido tiobarbitúrico e interleucinas pró e anti-inflamatórias. Resultados: Foi observada menor concentração de substâncias reativas ao ácido tiobarbitúrico (0,20±0,05 vs. 0,27±0,05, P=0,014) e menor dano histopatológico e edema no tecido cardíaco do grupo tratado com N-acetilcisteína em relação ao grupo cuja reposição volêmica ocorreu somente com Ringer Lactato. Não foi observada diferença da expressão das citocinas interleucina 6 (2.138,29±316,89 vs. 1.870,16±303,68, P=0,091) e interleucina 10 (1.019,83±262,50 vs. 848,60±106,5, P=0,169) entre os grupos tratados. Conclusão: A associação da N-acetilcisteína na reposição volêmica atenua o estresse oxidativo no coração, assim como dano e edema miocárdicos, porém, não modifica a expressão de citocinas inflamatórias. .

Animals , Male , Acetylcysteine/pharmacology , Free Radical Scavengers/pharmacology , Heart/drug effects , Shock, Hemorrhagic/drug therapy , Arterial Pressure , Acetylcysteine/therapeutic use , Fluid Therapy/methods , Free Radical Scavengers/therapeutic use , /analysis , /analysis , Isotonic Solutions/pharmacology , Isotonic Solutions/therapeutic use , Lactic Acid/blood , Myocardium/metabolism , Myocardium/pathology , Oxidative Stress/drug effects , Potassium/blood , Random Allocation , Rats, Wistar , Reproducibility of Results , Reperfusion Injury/prevention & control , Resuscitation/methods , Shock, Hemorrhagic/metabolism , Time Factors , Thiobarbiturates/analysis
Arch. endocrinol. metab. (Online) ; 59(1): 66-70, 02/2015. graf
Article in English | LILACS | ID: lil-746441


Objective Obstructive sleep apnea is a common disorder associated with aging and obesity. Apneas cause repeated arousals, intermittent hypoxia, and oxidative stress. Changes in glucolipidic profile occur in apnea patients, independently of obesity. Animal models of sleep apnea induce hyperglycemia. This study aims to evaluate the effect of the antioxidants melatonin and N-acetylcysteine on glucose, triglyceride, and cholesterol levels in animals exposed to intermittent hypoxia. Materials and methods Two groups of Balb/c mice were exposed to intermittent hypoxia (n = 36) or sham intermittent hypoxia (n = 36) for 35 days. The intermittent hypoxia group underwent a total of 480 cycles of 30 seconds reducing the inspired oxygen fraction from 21% to 7 ± 1% followed by 30 seconds of normoxia, during 8 hours daily. Melatonin or N-acetylcysteine were injected intraperitonially daily from day 21 on. Results At day 35, glucose levels were significantly higher in the intermittent hypoxia group than in the control group. The intermittent hypoxia groups receiving N-acetylcysteine and vehicle showed higher glucose levels than the group receiving melatonin. The lipid profile was not affected by intermittent hypoxia or antioxidant administration. Conclusions The present results suggest that melatonin prevents the well-recognized increase in glucose levels that usually follows exposure to intermittent hypoxia. Further exploration of the role of melatonin in sleep apnea is warranted. Arch Endocrinol Metab. 2015;59(1):66-70 .

Animals , Hypoxia/drug therapy , Antioxidants/pharmacology , Hyperglycemia/drug therapy , Melatonin/pharmacology , Sleep Apnea, Obstructive/drug therapy , Acetylcysteine/pharmacology , Hypoxia/blood , Blood Glucose/analysis , Body Weight/drug effects , Cholesterol/blood , Disease Models, Animal , Free Radical Scavengers/pharmacology , Mice, Inbred BALB C , Time Factors , Triglycerides/blood
Biol. Res ; 48: 1-11, 2015. graf, tab
Article in English | LILACS | ID: biblio-950785


BACKGROUND: Atriplex laciniata L. was investigated for phenolic, flavonoid contents, antioxidant, anticholinesterase activities, in an attempt to explore its effectiveness in Alzheimer's and other neurological disorders. Plant crude methanolic extract (Al.MeF), subsequent fractions; n-hexane (Al.HxF), chloroform (Al.CfF), ethyl acetate (Al.EaF), aqueous (Al.WtF), Saponins (Al.SPF) and Flavonoids (Al.FLVF) were investigated for DPPH, ABTS and H2O2 free radical scavenging activities. Further these extracts were subjected to acetylcholinesterase (AChE) & butyrylcholinesterase (BChE) inhibitory activities using Ellman's assay. Phenolic and Flavonoid contents were determined and expressed in mg Gallic acid GAE/g and Rutin RTE/g of samples respectively. RESULTS: In DPPH free radicals scavenging assay, Al.FLVF, Al.SPF and Al.MeF showed highest activity causing 89.41 ± 0.55, 83.37 ± 0.34 and 83.37 ± 0.34% inhibition of free radicals respectively at 1 mg/mL concentration. IC50 for these fractions were 33, 83 and 82 µg/mL respectively. Similarly, plant extracts showed high ABTS scavenging potential, i.e. Al.FLVF (90.34 ± 0.55), Al.CfF (83.42 ± 0.57), Al.MeF (81.49 ± 0.60) with IC50 of 30, 190 and 70 µg/ml respectively. further, H2O2 percent scavenging was highly appraised in Al.FLVF (91.29 ±0.53, IC50 75), Al.SPF (85.35 ±0.61, IC50 70) and Al.EaF (83.48 ± 0.67, IC50 270 µg/mL). All fractions exhibited concentration dependent AChE inhibitory activity as; Al.FLVF, 88.31 ± 0.57 (IC50 70 µg/mL), Al.SPF, 84.36 ± 0.64 (IC50 90 µg/mL), Al.MeF, 78.65 ± 0.70 (IC50 280 µg/mL), Al.EaF, 77.45 ± 0.46 (IC50 270 µg/mL) and Al.WtF 72.44 ± 0.58 (IC50 263 µg/mL) at 1 mg/mL. Likewise the percent BChE inhibitory activity was most obvious in Al.FLVF 85.46 ± 0.62 (IC50 100 µg/mL), Al.CfF 83.49 ± 0.46 (IC50 160 µg/mL), Al.MeF 82.68 ± 0.60 (IC50 220 µg/mL) and Al.SPF 80.37 ± 0.54 (IC50 120 µg/mL). CONCLUSIONS: These results stipulate that A. laciniata is enriched with phenolic and flavonoid contents that possess significant antioxidant and anticholinestrase effects. This provide pharmacological basis for the presence of compounds that may be effective in Alzheimer's and other neurological disorders.

Saponins/metabolism , Flavonoids/metabolism , Plant Extracts/pharmacology , Cholinesterase Inhibitors/pharmacology , Atriplex/chemistry , Alzheimer Disease/drug therapy , Antioxidants/pharmacology , Phenols/analysis , Phenols/metabolism , Acetylcholinesterase/metabolism , Saponins/isolation & purification , Spectrophotometry , Sulfonic Acids/metabolism , Flavonoids/analysis , Butyrylcholinesterase/metabolism , Cholinesterase Inhibitors/isolation & purification , Free Radical Scavengers/pharmacology , Oxidative Stress/drug effects , Inhibitory Concentration 50 , Benzothiazoles/metabolism , Medicine, Traditional , Antioxidants/isolation & purification
Biol. Res ; 48: 1-17, 2015. graf, tab
Article in English | LILACS | ID: biblio-950779


BACKGROUND: Excessive production of free radicals causes direct damage to biological molecules such as DNA, proteins, lipids, carbohydrates leading to tumor development and progression. Natural antioxidant molecules from phytochemicals of plant origin may directly inhibit either their production or limit their propagation or destroy them to protect the system. In the present study, Monodora myristica a non-timber forest product consumed in Cameroon as spice was screened for its free radical scavenging properties, antioxidant and enzymes protective activities. Its phenolic compound profile was also realized by HPLC. RESULTS: This study demonstrated that M. myristica has scavenging properties against DPPH',OH',NO', and ABTS'radicals which vary in a dose depending manner. It also showed an antioxidant potential that was comparable with that of Butylated Hydroxytoluene (BHT) and vitamin C used as standard. The aqueous ethanol extract of M. myristica barks (AEH); showed a significantly higher content in polyphenolic compounds (21.44 ± 0.24 mg caffeic acid/g dried extract) and flavonoid (5.69 ± 0.07 quercetin equivalent mg/g of dried weight) as compared to the other studied extracts. The HPLC analysis of the barks and leaves revealed the presence of several polyphenols. The acids (3,4-OH-benzoic, caffeic, gallic, O- and P- coumaric, syringic, vanillic), alcohols (tyrosol and OH-tyrosol), theobromine, quercetin, rutin, catechine and apigenin were the identified and quantified polyphenols. All the tested extracts demonstrated a high protective potential on the superoxide dismutase (SOD), catalase and peroxidase activities. CONCLUSION: Finally, the different extracts from M. myristica and specifically the aqueous ethanol extract reveal several properties such as higher free radical scavenging properties, significant antioxidant capacities and protective potential effects on liver enzymes.

Plant Extracts/pharmacology , Free Radical Scavengers/pharmacology , Spices , Annonaceae/chemistry , Polyphenols/chemistry , Antioxidants/pharmacology , Peroxidases/drug effects , Picrates/metabolism , Sulfonic Acids/metabolism , Superoxide Dismutase/drug effects , Flavonoids/analysis , Biphenyl Compounds/metabolism , In Vitro Techniques , Cameroon , Plant Extracts/chemistry , Catalase/drug effects , Forests , Chromatography, High Pressure Liquid , Hydroxyl Radical/metabolism , Plant Leaves/chemistry , Plant Bark/chemistry , Benzothiazoles/metabolism , Nitric Oxide/metabolism
Indian J Exp Biol ; 2014 Nov; 52(11): 1062-1070
Article in English | IMSEAR | ID: sea-153788


Antimicrobial screening of several novel 4-thiazolidinones with benzothiazole moiety has been performed. These compounds were evaluated for antimicrobial activity against a panel of bacterial and fungal strains. The strains were treated with these benzothiazole derivatives at varying concentrations, and MIC’s were calculated. Structures of these compounds have been determined by spectroscopic studies viz., FT-IR, 1H NMR, 13C NMR and elemental analysis. Significant antimicrobial activity was observed for some members of the series, and compounds viz. 3-(4-(benzo[d]thiazol-2-yl) phenyl)-2-(4-methoxyphenyl)thiazolidin-4-one and 3-(4-(benzo[d]thiazol-2-yl)phenyl)-2-(4-hydroxy phenyl)thiazolidin-4-one were found to be the most active against E.coli and C.albicans with MIC values in the range of 15.6–125 μg/ml. Preliminary study of the structure–activity relationship revealed that electron donating groups associated with thiazolidine bearing benzothiazole rings had a great effect on the antimicrobial activity of these compounds and contributes positively for the action. DNA cleavage experiments gave valuable hints with supporting evidence for describing the mechanism of action and hence showed a good correlation between their calculated MIC’s and its lethality.

Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Benzothiazoles/chemical synthesis , Benzothiazoles/chemistry , Benzothiazoles/pharmacology , Candida/drug effects , DNA, Bacterial/drug effects , DNA, Circular/drug effects , Disk Diffusion Antimicrobial Tests , Drug Evaluation, Preclinical , Electrophoresis, Agar Gel , Free Radical Scavengers/pharmacology , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Microbial Sensitivity Tests , Molecular Structure , Thiazolidines/chemical synthesis , Thiazolidines/chemistry , Thiazolidines/pharmacology
Acta cir. bras ; 29(7): 445-449, 07/2014. tab, graf
Article in English | LILACS | ID: lil-714569


PURPOSE: To investigate if expression of genes encoding pro and anti-apoptotic proteins in the rat enteric endothelial cells stimulated by intestinal ischemia followed by reperfusion (IR) can be modified by treatment with heparin (HP). METHODS: Eighteen adult Wistar rats were divided in three groups: sham group submitted to laparotomy only (SG), ischemia followed by reperfusion group (IRG); ischemia followed by reperfusion plus pretreatment with HP 100 (IRG+HP). Ischemia was performed by clamping of the superior mesenteric artery. After 60 min of ischemia, metal clamps were removed for reperfusion for 120 min. Gene expression of encoding pro (Casp1, Casp6, Casp3, Cflar, Fas and Pgl) and anti-apoptotic (Bcl2, Bcl2l1 and Naip2) proteins in rat enteric endothelial cells was evaluated by PCR microarray method. RESULTS: Compared to rat endothelial cells of SG, the expression of pro-apoptotic genes was up-regulated in IRG while anti-apoptotic genes were down-regulated. In contrast, the expression of anti-apoptotic genes in IRG+HP was up-regulated while pro-apoptotic genes was down-regulated compared to SG. CONCLUSION: The attenuation by heparin of intestinal ischemia-reperfusion previously demonstrated in rodents could be related with ability of this drug to stimulate and reduce gene expression of encoding anti and pro-apoptotic proteins, respectively. .

Animals , Male , Apoptosis Regulatory Proteins/drug effects , Endothelial Cells/drug effects , Gene Expression/drug effects , Heparin/pharmacology , Intestines/blood supply , Ischemia/drug therapy , Reperfusion Injury/drug therapy , Apoptosis Regulatory Proteins/genetics , Constriction , Down-Regulation , Endothelial Cells/pathology , Free Radical Scavengers/pharmacology , Intestines/pathology , Ischemia/pathology , Mesenteric Artery, Superior , Rats, Wistar , Real-Time Polymerase Chain Reaction , Reproducibility of Results , Reperfusion Injury/pathology , Time Factors , Treatment Outcome , Up-Regulation
Braz. j. med. biol. res ; 47(5): 398-402, 02/05/2014. graf
Article in English | LILACS | ID: lil-709435


Morphine is a potent analgesic opioid used extensively for pain treatment. During the last decade, global consumption grew more than 4-fold. However, molecular mechanisms elicited by morphine are not totally understood. Thus, a growing literature indicates that there are additional actions to the analgesic effect. Previous studies about morphine and oxidative stress are controversial and used concentrations outside the range of clinical practice. Therefore, in this study, we hypothesized that a therapeutic concentration of morphine (1 μM) would show a protective effect in a traditional model of oxidative stress. We exposed the C6 glioma cell line to hydrogen peroxide (H2O2) and/or morphine for 24 h and evaluated cell viability, lipid peroxidation, and levels of sulfhydryl groups (an indicator of the redox state of the cell). Morphine did not prevent the decrease in cell viability provoked by H2O2 but partially prevented lipid peroxidation caused by 0.0025% H2O2 (a concentration allowing more than 90% cell viability). Interestingly, this opioid did not alter the increased levels of sulfhydryl groups produced by exposure to 0.0025% H2O2, opening the possibility that alternative molecular mechanisms (a direct scavenging activity or the inhibition of NAPDH oxidase) may explain the protective effect registered in the lipid peroxidation assay. Our results demonstrate, for the first time, that morphine in usual analgesic doses may contribute to minimizing oxidative stress in cells of glial origin. This study supports the importance of employing concentrations similar to those used in clinical practice for a better approximation between experimental models and the clinical setting.

Animals , Rats , Analgesics, Opioid/pharmacology , Glioma/drug therapy , Hydrogen Peroxide/administration & dosage , Morphine/pharmacology , Oxidative Stress/drug effects , Cell Line, Tumor , Cell Survival , Free Radical Scavengers/pharmacology , Glioma/metabolism , Lipid Peroxidation/drug effects , Models, Biological , Morphine/administration & dosage , Oxidation-Reduction , Protective Factors , Sulfhydryl Compounds/analysis
Braz. j. med. biol. res ; 47(3): 231-236, 03/2014. graf
Article in English | LILACS | ID: lil-704623


Studies have shown that edaravone may prevent liver injury. This study aimed to investigate the effects of edaravone on the liver injury induced by D-galactosamine (GalN) and lipopolysaccharide (LPS) in female BALB/c mice. Edaravone was injected into mice 30 min before and 4 h after GalN/LPS injection. The survival rate was determined within the first 24 h. Animals were killed 8 h after GalN/LPS injection, and liver injury was biochemically and histologically assessed. Hepatocyte apoptosis was measured by TUNEL staining; proinflammatory cytokines [tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)] in the liver were assayed by ELISA; expression of caspase-8 and caspase-3 proteins was detected by Western blot assay; and caspase-3 activity was also determined. Results showed that GalN/LPS induced marked elevations in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Edaravone significantly inhibited elevation of serum AST and ALT, accompanied by an improvement in histological findings. Edaravone lowered the levels of TNF-α and IL-6 and reduced the number of TUNEL-positive cells. In addition, 24 h after edaravone treatment, caspase-3 activity and mortality were reduced. Edaravone may effectively ameliorate GalN/LPS-induced liver injury in mice by reducing proinflammatory cytokines and inhibiting apoptosis.

Animals , Female , Antipyrine/analogs & derivatives , Apoptosis/drug effects , Cytokines/drug effects , Chemical and Drug Induced Liver Injury/prevention & control , Free Radical Scavengers/pharmacology , Alanine Transaminase/blood , Antipyrine/pharmacology , Aspartate Aminotransferases/blood , /analysis , /metabolism , /analysis , Chemical and Drug Induced Liver Injury/physiopathology , Enzyme-Linked Immunosorbent Assay , Endotoxins/toxicity , Galactosamine/toxicity , Hepatocytes/drug effects , In Situ Nick-End Labeling , /analysis , Lipopolysaccharides/toxicity , Mice, Inbred BALB C , Random Allocation , Tumor Necrosis Factor-alpha/analysis
Indian J Exp Biol ; 2014 Feb; 52(2): 133-138
Article in English | IMSEAR | ID: sea-150341


Free radical scavenging activity, ferrous ion chelating capacity, reducing power and genoprotective effect of the aqueous leaf extracts of four unexplored endemic Curcuma spp. (C. vamana, C. neilgherrensis, C. mutabilis, C. haritha) were found to be dose-dependent and were highest in C. vamana. DNA protection property of the extracts was evaluated against H2O2/UV-induced oxidative damage. DNA-methyl green displacement assay showed that these extracts were free of DNA intercalating compounds. Further, hemolysis assay also showed that the extracts were non-toxic to human erythrocytes. The results highlight C. vamana as a promising source for herbal preparations possessing high antioxidant potential and genoprotective activity.

Antioxidants/pharmacology , Curcuma/chemistry , DNA Damage/drug effects , DNA, Plant/drug effects , Free Radical Scavengers/metabolism , Free Radical Scavengers/pharmacology , Humans , Iron Chelating Agents/metabolism , Iron Chelating Agents/pharmacology , Oxidative Stress/drug effects , Physarum polycephalum/drug effects , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Leaves/chemistry
Korean Journal of Urology ; : 756-763, 2014.
Article in English | WPRIM | ID: wpr-227268


PURPOSE: Limited studies have shown antifibrotic effects of pentoxifylline, captopril, simvastatin, and tamoxifen. No comparisons are available of the effects of these drugs on prevention of renal and bladder changes in partial urethral obstruction (PUO). MATERIALS AND METHODS: The rats were divided into six groups (n=7). The sham-operated rats (group I) only underwent laparotomy and did not receive any treatments. The PUO groups (group II-VI) received normal saline (PUO+NS), pentoxifylline (100 mg/kg/d; PUO+PEN), captopril (35 mg/kg/d; PUO+CAP), simvastatin (15 mg/kg/d; PUO+SIM), or tamoxifen (10 mg/kg/d; PUO+TAM) by gavage for 28 days. Then, the volume and/or length of the kidney components (tubules, vessels, and fibrous tissue) and the bladder components (epithelial and muscular layers, fibrous tissue, fibroblast and fibrocyte number) were quantitatively evaluated on the microscopic sections by use of stereological techniques. RESULTS: The volume of renal and bladder fibrosis was significantly ameliorated in the PUO+PEN group, followed by the PUO+CAP, PUO+SIM, and PUO+TAM groups. Also, the volume and length of the renal tubules and vessels and bladder layers were more significantly protected in the PUO+PEN group, followed by the PUO+CAP, PUO+SIM, and PUO+TAM groups. CONCLUSIONS: Treatment of PUO with PEN was more effective in the prevention of renal and bladder fibrosis and in the preservation of renal and bladder structures.

Angiotensin-Converting Enzyme Inhibitors/pharmacology , Animals , Captopril/pharmacology , Disease Models, Animal , Estrogen Antagonists/pharmacology , Free Radical Scavengers/pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Kidney/drug effects , Male , Pentoxifylline/pharmacology , Rats , Simvastatin/pharmacology , Tamoxifen/pharmacology , Urethral Obstruction/drug therapy , Urinary Bladder Neck Obstruction/drug therapy