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1.
Braz. j. biol ; 84: e250936, 2024. graf
Article in English | MEDLINE, LILACS, VETINDEX | ID: biblio-1345557

ABSTRACT

Abstract This study was carried out to evaluate the effect of Glutamine, as a dipeptide or a free amino acid form, on the progression of burn injuries in rats. Thirty male Wistar rats were burned with a comb metal plate heated in boiling water (98 °C) for three minutes, creating four rectangular full-thickness burn areas separated by three unburned interspaces (zone of stasis) in both dorsum sides. The animals were randomized into three groups (n=10): saline solution (G1-Control) and treated groups that orally received Glutamine as dipeptide (G2-Dip) or free amino acid (G3-FreeAA). Two and seven days after burn injury, lesions were photographed for unburned interspaces necrosis evolution assessment. Seven days after injury, glutathione seric was measured and histopathological analysis was performed. By photographs, there was a significant reduction in necrosis progression in G3-Free-AA between days two and seven. Histopathological analysis at day 7 showed a significantly higher stasis zone without necrosis and a higher number of fibroblasts in G2-Dip and G3-FreeAA compared with G1-Control. Also, glutathione serum dosage was higher in G2-Dip. The plasmatic glutathione levels were higher in the G2-Dip than the G1-Control, and there was a trend to higher levels in G3-FreeAA. The reduction in histological lesions, greater production of fibroblasts, and greater amounts of glutathione may have benefited the evolution of burn necrosis, which showed greater preservation of interspaces.


Resumo Este estudo foi realizado para avaliar o efeito da Glutamina, como um dipeptídeo ou forma de aminoácido livre, na progressão de queimaduras em ratos. Trinta ratos Wistar machos foram queimados com um pente de metal aquecido em água fervente (98 °C) por três minutos, criando quatro áreas retangulares queimadas separadas por três interesespaços não queimados (zona de estase) em ambos os lados do dorso. Os animais foram randomizados em três grupos (n = 10): solução salina (G1-Controle) e grupos tratados que receberam glutamina via oral como dipeptídeo (G2-Dip) ou aminoácido livre (G3-FreeAA). Dois e sete dias após a queimadura, as lesões foram fotografadas para avaliação da evolução da necrose entre os espaços não queimados. Sete dias após a lesão, foi dosada a glutationa sérica e realizada análise histopatológica. Pelas fotografias, houve uma redução significativa na progressão da necrose no G3-Free-AA entre os dias dois e sete. A análise histopatológica no dia 7 mostrou uma zona de estase significativamente maior sem necrose e número mais elevado de fibroblastos em G2-Dip e G3-FreeAA em comparação com G1-Controle. Os níveis plasmáticos de glutationa foram maiores no G2-Dip em relação ao G1-Controle, e houve tendência a níveis mais elevados no G3-FreeAA. A redução das lesões histológicas, maior produção de fibroblastos, maior quantidade de glutationa podem ter beneficiado a evolução da necrose da queimadura, que mostrou maior preservação dos interespaços.


Subject(s)
Animals , Male , Rats , Burns/drug therapy , Glutamine , Rats, Wistar , Dipeptides , Disease Models, Animal , Amino Acids
2.
Braz. j. biol ; 83: e248032, 2023. graf
Article in English | MEDLINE, LILACS, VETINDEX | ID: biblio-1278557

ABSTRACT

Abstract A new species of nematode parasite of the subfamily Pudicinae (Heligmosomoidea: Heligmonellidae) is described from the small intestine of Proechimys simonsi (Rodentia: Echimyidae) from the locality of Nova Cintra in the municpality of Rodrigues Alves, Acre state, Brazil. The genus Pudica includes 15 species parasites of Neotropical rodents of the families Caviidae, Ctenomyidae, Dasyproctidae, Echimyidae, Erethizontidae, and Myocastoridae. Four species of this nematode were found parasitizing three different species rodents of the genus Proechimys in the Amazon biome. Pudica wandiquei n. sp. can be differentiated from all other Pudica species by the distance between the ends of rays 6 and 8 and the 1-3-1 pattern of the caudal bursa in both lobes.


Resumo Uma nova espécie de nematódeo da subfamília Pudicinae (Heligmosomoidea: Heligmonellidae) é descrito parasitando o intestino delgado de Proechimys simonsi (Rodentia: Echimyidae) em Nova Cintra, município de Rodrigues Alves, Estado do Acre, Brasil. O gênero Pudica inclui 15 espécies parasitas de roedores Neotropicais das famílias: Caviidae, Ctenomyidae, Dasyproctidae, Echimyidae, Erethizontidae e Myocastoridae. Destas, quatro espécies de nematódeos foram encontradas parasitando três diferentes espécies do roedor Proechimys no bioma Amazônia. Pudica wandiquei n. sp. é diferente das outras espécies de Pudica pela distância entre os raios 6 e 8 e pelo tipo da bolsa caudal, que é 1-3-1 em ambos os lados.


Subject(s)
Animals , Parasites , Trichostrongyloidea , Nematoda , Rodentia , Brazil
3.
Braz. j. biol ; 83: e237412, 2023. tab, graf
Article in English | MEDLINE, LILACS, VETINDEX | ID: biblio-1355854

ABSTRACT

Abstract Only few studies have focus on animals that received Pilocarpine (Pilo) and did not develop behavioral status epilepticus (SE) and, whether they may become epileptic in the model's chronic phase. Previews works observed mossy fiber sprouting in the hippocampus of Non-SE (NSE) rats, while others observed spontaneous and recurrent seizures (SRS) 6 - 8 months after animals received Pilo. It is known that neuronal excitability is influenced by female hormones, as well as, the occurrence of SE in castrated and non-castrated female rats. However, it is not known whether females that received Pilo and did not show SE, may have SRS. The aim of this work was to investigate whether castrated and non-castrated female rats that did not show behavioral SE after Pilo, will develop SRS in the following one-year. For that, animals received 360 mg/kg of Pilo and were video monitored for 12 months. SE females from castrated and non-castrated groups became epileptic since the first month after drug injection. Epileptic behaviors were identified watching video monitoring recordings in the fast speed. Castrated and Non-castrated NSE animals showed behaviors resembling seizures described by Racine Scale stages 1 - 3. Motor alterations showed by NSE groups could be observed only when recordings were analyzed in slow speed. In addition, behavioral manifestations as, rhythmic head movements, sudden head movements, whole body movements and immobility were also observed in both, SE and NSE groups. We concluded that NSE female rats may have become epileptic. Adding to it, slow speed analysis of motor alterations was essential for the observation of NSE findings, which suggests that possibly many motor alterations have been underestimated in epilepsy experimental research.


Resumo Poucos são os estudos com foco em animais que receberam Pilocarpina (Pilo) e não desenvolveram status epilepticus (SE) comportamental e, se os mesmos se tornarão epilépticos na fase crônica do modelo. Autores observaram o brotamento das fibras musgosas no hipocampo de ratos Não-SE (NSE), enquanto outros observaram crises espontâneas e recorrentes (CER) 6 - 8 meses após receberam a droga. A excitabilidade neuronal é influenciada pelos hormônios femininos e, da mesma forma, a ocorrência de SE em ratas castradas e não-castradas. Entretanto, não é sabido se as fêmeas que não apresentam SE terão CER. O objetivo deste trabalho foi investigar se fêmeas castradas e não castradas que não tiveram SE comportamental após a injeção de Pilo desenvolverão CER dentro de um ano. Para isto, os animais receberam 360 mg/kg de Pilo e foram videomonitorados por 12 meses. As fêmeas SE castradas e não-castradas se tornaram epilépticas desde o primeiro mês pós Pilo. O comportamento epiléptico foi identificado assistindo as gravações na velocidade rápida. As fêmeas NSE castradas e não-castradas apresentaram comportamentos similares aos estágios 1 - 3 da Escala de Racine. As alterações motoras nestes grupos (NSE) foram observadas apenas quando as videomonitoração foi analisada na velocidade lenta. Além destas, manifestações comportamentais como movimentos rítmicos da cabeça, movimentos súbitos da cabeça, movimentos de todo o corpo e imobilidade também foram observadas em ambos grupos, SE e NSE. Concluímos que as fêmeas NE podem ter se tornado epilépticas. Adicionado a isto, a análise das alterações motoras na velocidade lenta foi essencial para a observação dos achados das fêmeas NSE, o que sugere que possivelmente muitas alterações motoras têm sido subestimados na pesquisa em epilepsia experimental.


Subject(s)
Animals , Female , Rats , Pilocarpine/toxicity , Seizures/chemically induced , Status Epilepticus/chemically induced , Rats, Wistar , Muscarinic Agonists/toxicity , Models, Theoretical
4.
Int. j. cardiovasc. sci. (Impr.) ; 35(2): 214-219, Mar.-Apr. 2022. tab
Article in English | LILACS-Express | LILACS | ID: biblio-1364976

ABSTRACT

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.

6.
Braz. j. otorhinolaryngol. (Impr.) ; 88(1): 28-35, Jan.-Feb. 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1364575

ABSTRACT

Abstract Introduction Considering that previous studies suggest that pesticides may cause hearing disorders in humans, as well as the lack of studies proving the specific mechanisms of injury and the difficulty of separating concomitant etiological factors of the hearing damage, such as noise and vibration, it is important to develop studies using animal models to elucidate the effects of exposure to those substances isolated from other hearing damage etiologies. Objective To evaluate if the exposure to a dichlorvos based organophosphorus insecticide may induce ototoxicity. Methods 36 male Wistar rats were assigned to 3 groups (12 rats/group): control (exposed to water), positive control (treated with cisplatin to induce hearing damage) and experimental (exposed to dichlorvos based organophosphorus insecticide). The amplitude of distortion product otoacoustic emissions in the frequencies of 4, 6, 8, 10 and 12 kHz was evaluated before and after exposure, as well as systemic toxicity signs, body mass gain and plasma cholinesterase. Open field and plus maze tests were performed in 24 rats: experimental (n = 8), control (n = 8) and positive control group (n = 8 introduced new rats to induce anxiolytic activity) to evaluate the locomotor activity and anxiety, respectively. Results There was no significant change in body mass gain and plasma cholinesterase in the dichlorvos based organophosphorus insecticide group, however, the animals showed transient piloerection, depression and dyspnea during exposure. The behavior was not affected in any group. The frequencies of 8 and 10 kHz were significantly affected bilaterally in the insecticide group, which also showed a significant difference of the control in 10 kHz on the right and 8 and 10 kHz on the left ear. Conclusion Subchronic inhalation exposure to dichlorvos based organophosphorus insecticide induced ototoxicity in the cochlear function of rats without relevant systemic toxicity.


Resumo Introdução Considerando que estudos anteriores sugerem que pesticidas podem causar distúrbios auditivos em humanos, além da falta de estudos que comprovem os mecanismos específicos de lesão e a dificuldade em separar fatores etiológicos concomitantes dos danos auditivos, como ruído e vibração, é importante desenvolver estudos que usem modelos animais para elucidar os efeitos da exposição a substâncias isoladas de outras etiologias de danos auditivos. Objetivo Avaliar se a exposição a um inseticida organofosforado baseado em diclorvos pode induzir ototoxicidade. Método Foram divididos em 3 grupos 36 ratos Wistar machos (12 ratos/grupo): controle (exposto à água), controle positivo (tratado com cisplatina para induzir dano auditivo) e experimental (exposto ao inseticida). A amplitude das emissões otoacústicas por produto de distorção nas frequências de 4, 6, 8, 10 e 12 kHz foi avaliada antes e após a exposição, bem como sinais de toxicidade sistêmica, ganho de massa corporal e colinesterase plasmática. Os testes Open Field e Plus Maze foram feitos em 24 ratos: experimental (n = 8), controle (n = 8) e grupo controle positivo (n = 8, introduziu novos ratos para induzir atividade ansiolítica) para avaliar a atividade locomotora e a ansiedade, respectivamente. Resultados Não houve alteração significativa no ganho de massa corporal e colinesterase plasmática no grupo experimental; entretanto, os animais apresentaram piloereção transitória, depressão e dispneia durante a exposição. O comportamento não foi afetado em qualquer grupo. As frequências de 8 e 10 kHz foram significativamente afetadas bilateralmente no grupo exposto ao inseticida, o qual também mostrou uma diferença significativa do controle em 10 kHz na orelha direita e 8 e 10 kHz na orelha esquerda. Conclusão A exposição subcrônica inalatória de inseticida organofosforado baseado em diclorvos induziu ototoxicidade na função coclear de ratos sem toxicidade sistêmica relevante.

7.
Acta sci., Health sci ; 44: e58558, Jan. 14, 2022.
Article in English | LILACS-Express | LILACS | ID: biblio-1367771

ABSTRACT

Cardiovascular disease(CVD) remains the major cause of mortality in the world, typically claiming a third of all deaths. The primary cause of CVD is atherosclerosis. Therefore, timely prevention and therapy of atherosclerosis are able to reduce the risk of the development of its clinical manifestations. Anti-atherosclerotic activity of medicinal plants mainly appears in their multiple effects.This study was carried out to evaluate the hypolipidemic activity of virgin olive oil in experimentally induced hyperlipemic Wistar. A total of 24 rats were randomly allocated to 4 equal groups and treated as follows for 50 days: (1) Normal control (NC); that were fed with a standart diet; (2) High Cholesterol Diet Control (HCD); which received high cholesterol diet for 50 days; (3) Animals receiving high cholesterol diet for 50 days, after this period the animals are fed for eight days by the standard foodand receiving by gavage virgin olive oil (HCD+VOO) and(4) Animals fed for eight days with the standard food and receiving by gavage olive oil (VOO). High Cholesterol Diet containing yolk egg and coconut oil. Results showed that olive oil caused a significant (p < 0.01) reduction in serum levels of Total Cholesterol (TC), Triglycerides (TG), Low­Density Lipoprotein Cholesterol (LDL) and Atherogenic Index Serum (AIS). The results also demonstrated a significant (p < 0.01) increase in High­Density Lipoprotein Cholesterol (HDL). Moreover, virgin olive oil induced a significant reduction in liver lipid content. On the other hand, a High cholesterol diet induced oxidative stress was measured by estimating reduced glutathione level and amount of thiobarbituric acid reactive substances (TBARS) formed as an index of lipid peroxidation in a liver and a heart. Virgin olive oil supplementation attenuated all these variations. Our observations of the study indicate that the virgin olive oil has a significant antihyperlipidemic potential.

8.
Braz. oral res. (Online) ; 36: e024, 2022. tab, graf
Article in English | LILACS-Express | LILACS, BBO | ID: biblio-1360251

ABSTRACT

Abstract: The aim of this study was to use microscopic and molecular techniques to evaluate the effects of a single session of antimicrobial photodynamic therapy (aPDT) on the alveolar repair process after tooth extraction in rats. The study sample included 84 rats divided into four groups, as follows: a) Control - untreated socket; b) Laser - socket treated using photobiomodulation; c) TBO - socket treated with topic application of the photosensitizer agent, toluidine blue O (TBO); and d) aPDT - socket treated with TBO and laser irradiation. An additional rat was used for thermal mapping during socket irradiation. The animals were euthanatized at 6, 15, and 28 days after unilateral extraction of the upper incisor. Quantitative and qualitative analyses of the connective and bone tissues, blood clot, blood vessel, and inflammatory infiltrate were performed, and real-time polymerase chain reaction was used to study the expression of genes (collagen type I, osteocalcin, alkaline phosphatase [ALP], runt-related transcription factor 2 [RUNX2], and vascular endothelial growth factor [VEGF]) involved in the bone healing process. No statistically significant differences in microscopic and molecular outcomes were observed between the groups (p > 0.05). A positive correlation was seen to exist between blood clot and VEGF (p = 0.000), and a negative correlation was observed between bone tissue and ALP (p = 0.028) and blood vessel and VEGF (p = 0.018). A single session of aPDT in the dental extraction site did not influence the alveolar repair process in rats.

9.
Braz. j. biol ; 82: e238735, 2022. tab, graf
Article in English | LILACS | ID: biblio-1153486

ABSTRACT

Abstract Using wire mesh live traps distribution pattern of the Rattus rattus and Mus musculus in different shops of three districts of Malakand region, Pakistan were recorded from September 2014 to October 2015. Over all 103 rodents (Rattus rattus 86 and Mus musculus 17) were caught during in 0.04 trap success (2448 trap nights). Regression of daily captures on cumulative captures revealed an estimate of 103 rodents from all the sampled structures with an average of 3.55 rodents per shop. R. rattus; 83.4% of captures were numerically dominant in almost all types of shops sampled, and were significantly different than Mus musculus; 16.5% of captures. Both species were found together in some shops while they were mostly trapped from the separate shops. Male rodents outnumbered the females.


Resumo Usando o padrão de distribuição de armadilhas vivas de malha de arame do Rattus rattus e Mus musculus em diferentes lojas de três distritos da região de Malakand, o Paquistão foi registrado de setembro de 2014 a outubro de 2015. No total, 103 roedores (Rattus rattus 86 e Mus musculus 17) foram pegos durante em 0,04 armadilha de sucesso (2448 noites de armadilha). A regressão das capturas diárias em capturas cumulativas revelou uma estimativa de 103 roedores de todas as estruturas amostradas, com uma média de 3,55 roedores por loja. R. rattus; 83,4% das capturas foram numericamente dominantes em quase todos os tipos de lojas da amostra e foram significativamente diferentes do Mus musculus; 16,5% das capturas. Ambas as espécies foram encontradas juntas em algumas lojas, enquanto estavam na maior parte presas em lojas separadas. Os roedores machos eram mais numerosos do que as fêmeas.


Subject(s)
Animals , Male , Female , Rabbits , Rats , Rodent Diseases/epidemiology , Rodentia , Pakistan , Specimen Handling , Symbiosis
11.
Arq. bras. cardiol ; 118(2): 435-445, 2022. tab, graf
Article in English, Portuguese | LILACS | ID: biblio-1364333

ABSTRACT

Resumo Fundamento O pterostilbeno (PS), um composto polifenólico natural e antioxidante, surge como uma intervenção promissora para minimizar danos do infarto agudo do miocárdio (IAM). Objetivo Este estudo teve como objetivo avaliar o desempenho do PS na promoção da homeostase redox nos pulmões e no ventrículo direito (VD) de animais infartados. Métodos Ratos Wistar machos (60 dias de idade) foram randomizados em três grupos: SHAM, IAM (infarto) e IAM+PS (IAM + pterostilbeno). Sete dias após o procedimento de IAM, os ratos foram tratados com PS (100 mg/kg/dia) por gavagem por oito dias. Os animais foram depois sacrificados e os pulmões e VD foram coletados para análise do balanço redox (diferenças foram consideradas significativas quando p<0,05). Resultados Nossos resultados mostram que o IAM desencadeia a interrupção redox no VD e nos pulmões, o que pode contribuir para danos induzido pelo IAM nesses órgãos. Consistentemente, o PS mitigou o estresse oxidativo e restaurou as defesas antioxidantes (Glutationa - GSH nos pulmões: SHAM = 0,79 ± 0,07; IAM = 0,67 ± 0,05; IAM + PS = 0,86 ± 0,14; p<0,05), indicando seu papel protetor neste cenário. Conclusão Nosso trabalho evidencia o potencial do uso de PS como abordagem terapêutica adjuvante após IAM para proteção dos tecidos pulmonares e cardíacos direitos.


Abstract Background Pterostilbene (PS), a natural and antioxidant polyphenolic compound emerges as a promising intervention in improving the myocardial infarction (MI) damages. Objetives This study aimed to evaluate PS actions in promoting redox homeostasis in lungs and right ventricle (RV) of infarcted animals. Methods Male Wistar rats (60 day-old) were randomized into three groups: SHAM, MI (infarcted), and MI+PS (MI+pterostilbene). Seven days after MI procedure, rats were treated with PS (100 mg/kg/day) via gavage for eight days. Animals were euthanized and the lungs and RV were harvested for analyses of redox balance (Differences were considered significant when p<0.05). Results Our results show that MI triggers a redox disruption scenario in RV and lungs, which can contribute to MI-induced damage on these organs. Consistently, PS mitigated oxidative stress and restored antioxidant defenses (GSH in lungs: SHAM= 0.79±0.07; MI=0.67±0.05; MI+PS=0.86±0.14; p<0.05), indicating its protective role in this scenario. Conclusions Our work evidences the PS potential use as an adjuvant therapeutic approach after MI focusing on protecting pulmonary and right-sided heart tissues.


Subject(s)
Animals , Male , Rats , Stilbenes/pharmacology , Oxidative Stress/drug effects , Heart Ventricles/drug effects , Lung/drug effects , Myocardial Infarction/complications , Myocardial Infarction/drug therapy , Rats, Wistar
12.
China Pharmacy ; (12): 685-692, 2022.
Article in Chinese | WPRIM | ID: wpr-923003

ABSTRACT

OBJECTIVE To inv estigate the in vitro inhibitory effects of acteoside on cytochrome P 450(CYP)enzymes in liver microsomes of rats. METHODS Using probe substrates method ,acteoside(0.1,0.3,1,3,10,30 μmol/L)was incubated with probe substrates phenacetin ,mephentoin,diclofenac,coumarin,dextromethorphan and testosterone (substrates of CYP 1A2, CYP2C19,CYP2C9,CYP2A6,CYP2D6 and CYP 3A4 enzymes,respectively)in liver microsomes of rats. Another blank control group and positive inhibitor group [ α-naphthoflavone,ticlopidine,sulfabendazole,pilocarpine,quinidine and ketoconazole (inhibitors of CYP 1A2,CYP2C19,CYP2C9,CYP2A6,CYP2D6 and CYP 3A4 enzymes,respectively)] were set up. Using indapamide as the internal standard , the contents of corresponding metabolites (acetaminophen, 4-hydroxymephenytoin, 4-hydroxydiclofenac,7-hydroxycoumarin,dextran,6 β-hydroxytestosterone) were detected by ultra high performance liquid chromatography-tandem mass spectrometry . The IC 50 values were calculated by GraphPad v 8.0 software. By computer molecular docking technology ,acteoside and positive inhibitors were molecularly docked with the CYP enzyme ,and the binding mode and strength of the two molecules were analyzed. RESULTS The IC 50 values of acteoside to CYP 1A2 and CYP 2A6 enzymes were more than 30 μmol/L,and those of acteoside to CYP 2D6,CYP2C19,CYP2C9 and CYP 3A4 enzymes were 24.87,21.52,12.56 and 7.55 μmol/L,respectively. The hydrogen bond and hydrophobic force could form between acteoside and CYP 3A4 enzyme,and the hydrogen bond and electrostatic interaction could form between ketoconazole and CYP 3A4 enzyme. The binding free energy of acteoside and ketoconazole to CYP 3A4 enzyme were - 10.2 and - 12.4 kcal/mol (1 kcal/mol=4.19 kJ),respectively. CONCLUSIONS Acteoside shows moderate inhibitory effect on CYP 3A4 enzyme in liver microsomes of rats ,and its affinity is equivalent to that of positive inhibitor ;the compound shows weak inhibitory effect on other 5 CYP enzymes.

13.
Journal of Clinical Hepatology ; (12): 587-593, 2022.
Article in Chinese | WPRIM | ID: wpr-922959

ABSTRACT

Objective To investigate the effect of Shuganning injection (SGN) in alleviating drug-induced cholestasis and the possible mechanisms involved. Methods The liver of Sprague-Dawley rats was decellularized to prepare collagen scaffolds, and then the scaffolds were recellularized with human HepG2 cells to obtain the tissue-engineered liver (normal control group). The tissue-engineered liver was perfused with 10 μmol/L chlorpromazine (CPZ) and bile salt mixture to establish a model of drug-induced cholestasis (CPZ group), and the model was further treated with Shuganning injection (10 3 -fold dilution) as the injury protection group (SGN+CPZ group). The markers for hepatocellular injury [alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP)] and the antioxidant and oxidative stress markers [glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), and reactive oxygen species (ROS)] were measured for all groups, and the normal control group, the CPZ group, and the SGN+CPZ group were compared in terms of the mRNA and protein expression levels of the enzymes associated with liver bile salt metabolism and the enzymes associated with hepatic cholestasis. HE staining was performed to observe liver pathology. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results Compared with the CPZ group, the SGN+CPZ group had significant reductions in the markers for hepatocellular injury ALT, AST, LDH, and ALP (all P < 0.000 1), significant increases in the oxidative stress markers GSH and SOD ( P < 0.000 1 and P < 0.001), and significant reductions in the markers MDA and ROS ( P < 0.000 1 and P < 0.001). Compared with the CPZ group, the SGN+CPZ group had significant reductions in the mRNA expression levels of cholesterol 7α-hydroxylase (CYP7A1) and sterol 12α-hydroxylase (CPY8B1) in hepatocytes (all P < 0.001) and significant increases in the mRNA expression levels of farnesoid X receptor (FXR), small heterodimeric partner (SHP), bile salt export pump (BSEP), and multidrug resistance-associated protein 2 (MRP2) ( P < 0.000 1, P < 0.01, P < 0.000 1, and P < 0.000 1). HE staining showed that compared with the CPZ group, the SGN+CPZ group had a significant reduction in hepatocyte injury and a significant increase in the number of cells. Conclusion Shuganning injection can alleviate drug-induced cholestatic liver injury caused by chlorpromazine, and it exerts a protective effect by activating FXR in hepatocytes and increasing the expression of SHP to regulate bile salt balance. It also inhibits CYP7A1 and CYP8B1 to reduce the synthesis of hydrophobic bile acids and upregulates the expression of BSEP and MRP2 to promote the excretion of bile salts.

14.
Journal of Clinical Hepatology ; (12): 334-341, 2022.
Article in Chinese | WPRIM | ID: wpr-920880

ABSTRACT

Objective To investigate the intervention effect of GDC-0449, a hedgehog signaling pathway inhibitor, on rats with liver fibrosis induced by carbon tetrachloride (CCl 4 ) combined with 2-acetylaminofluorene (2-AAF). Methods A total of 18 female Fisher344 rats were randomly divided into normal group, CCl 4 /2-AAF group, and GDC-0449 group, with 6 rats in each group. The rats in the CCl 4 /2-AAF group and the GDC-0449 group were given subcutaneously injected 30% CCl 4 -olive oil solution at a dose of 2 mL/kg twice a week for 6 weeks to induce liver fibrosis; since week 7, in addition to the injection of CCl 4 -olive oil solution, the rats in these two groups were given 2-AAF (100 mg/kg/d) by gavage, and the rats in the GDC-0449 group were given GDC-0449 (25 mg/kg/d) by gavage, while those in the normal group were given an equal volume of olive oil solution by injection and normal saline by gavage. All rats were sacrificed at the end of week 9, and related samples were collected. HE staining and sirius red (SR) staining were used to observe the changes in liver histopathology and collagen deposition, and the semi-quantitative analysis of SR-positive area and Ishak score were used to evaluate fibrosis degree; the alkaline hydrolysis method was used to measure the level of hydroxyproline (Hyp) in liver tissue; immunohistochemistry, Western blot, and qRT-PCR were used to measure the expression of α-smooth muscle actin (α-SMA), type Ⅰ collagen (Col-Ⅰ), type Ⅳ collagen (Col-Ⅳ), cytokeratin 19 (CK19), cytokeratin 7 (CK7), the epithelial cell adhesion molecule Epcam, and the hedgehog signaling pathway in liver tissue; double immunofluorescence staining was used to observe the colocalization of CK19 and the oval cell marker OV6. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results Compared with the normal group, the CCl 4 /2-AAF group had marked inflammatory cell aggregation and collagen deposition in liver tissue, with the formation of a pseudolobular structure, as well as significant increases in Hyp level and collagen positive area ratio in liver tissue ( P < 0.05), Ishak score ( P < 0.05), and the expression of α-SMA, Col-Ⅰ, Col-Ⅳ, Epcam, CK19, CK7, the transmembrane transporter Smoothened (Smo), Hedgehog ligand Desert Hedgehog (Dhh), the Indian Hedgehog membrane-binding receptor Patched (Ptch2), and glioma-related oncogenes Gli1, Gli2, and Gli3 (all P < 0.05); double immunofluorescence staining showed that CK19-positive cells also expressed OV6 in the liver tissue of rats in the CCl 4 /2-AAF group, with a significant increase compared with the normal group. Compared with the CCl 4 /2-AAF group, the GDC-0449 group had significant reductions in inflammatory cell aggregation and collagen deposition in liver tissue, Hyp level and collagen positive area ratio in liver tissue ( P < 0.05), Ishak score ( P < 0.05), and the expression of α-SMA, Epcam, CK19, CK7, Smo, Ptch2, Gli1, Gli2, and Gli3 (all P < 0.05); double immunofluorescence staining showed a significant reduction in the number of cells with co-expression of OV6 and CK19 in liver tissue. Conclusion The Hedgehog signaling pathway inhibitor GDC-0449 can significantly inhibit the progression of liver fibrosis induced by CCl 4 /2-AAF in rats, possibly by inhibiting hepatic stellate cell activation, collagen deposition, activation and proliferation of hepatic progenitor cells, and differentiation of hepatic progenitor cells into biliary epithelial cells.

15.
Arq. bras. cardiol ; 117(6): 1134-1144, dez. 2021. graf
Article in Portuguese | LILACS | ID: biblio-1350046

ABSTRACT

Resumo Fundamento A cardiopatia isquêmica atraiu muito atenção devido às altas taxas de mortalidade, custos do tratamento e a crescente morbidade na população jovem. Estratégias de reperfusão reduziram a mortalidade. Porém, a reperfusão pode levar à morte do cardiomiócito e subsequente dano irreversível ao miocárdio. No momento, não há um tratamento eficiente e direcionado para a lesão de isquemia-reperfusão (I/R). Objetivos Avaliar se a dexmedetomidina (DEX) tem efeito protetivo na I/R do miocárdio e explorar os possíveis mecanismos por trás dela. Métodos Corações de ratos foram perfundidos com o sistema de perfusão de Langendorff e aleatoriamente distribuídos em cinco grupos: grupo controle, perfundido com solução de Krebs-Henseleit (K-H) por 205 minutos sem isquemia; e quatro grupos de teste que foram submetidos a 40 minutos de isquemia global e 120 minutos de reperfusão. O Grupo DEX, o grupo ioimbina (IO) e o grupo DEX + IO foram perfundidos com DEX (10 nM), IO (1 μM) ou a combinação de DEX e IO antes da reperfusão, respectivamente. A hemodinâmica cardíaca, o tamanho do infarto do miocárdio e a histologia do miocárdio foram avaliados. A expressão da proteína-78 regulada pela glicose (GRP78), a proteína quinase do retículo endoplasmático (PERK), a PERK fosforilada, o fator de iniciação eucariótico 2α (eIF2α), eIF2α fosforilado, o fator de transcrição 4 (TCF-4) e a proteína homóloga à proteína ligadora do acentuador CCAAT (CHOP) foram avaliados. P< 0,05 foi considerado para indicar a diferença estatisticamente significativa. Resultados O pré-condicionamento com DEX melhorou a função cardíaca nos corações com I/R, reduziu o infarto do miocárdio, a apoptose do miocárdio e a expressão de GRP78, p-PERK, eIF2α, p-eIF2α, TCF-4 e CHOP. Conclusões O pré-tratamento com DEX reduziu a lesão de I/R no miocárdio ao suprimir a apoptose, o que foi induzido pela via PERK.


Abstract Background Ischemic heart disease has attracted much attention due to its high mortality rates, treatment costs and the increasing morbidity in the young population. Strategies for reperfusion have reduced mortality. However, reperfusion can lead to cardiomyocyte death and subsequent irreversible myocardial damage. At present, the timely and targeted treatment of ischemia-reperfusion (I/R) injury is often lacking. Objectives To evaluate if dexmedetomidine (DEX) has a protective effect in myocardiual I/R and explore the possible mechanism behind it. Methods Rat hearts were perfused with a Langendorff perfusion system, and randomly assigned to five groups: control group, perfused with Krebs-Henseleit (K-H) solution for 205 minutes without ischemia; and four test groups that underwent 40 minutes of global ischemia and 120 min of reperfusion. The DEX group, the yohimbine (YOH) group and the DEX + YOH group were perfused with DEX (10 nM), YOH (1 μM) or the combination of DEX and YOH prior to reperfusion, respectively. Cardiac hemodynamics, myocardial infarct size, and myocardial histology were evaluated. The expression of glucose-related protein 78 (GRP78), protein kinase R-like ER kinase (PERK), phosphorylated PERK, eukaryotic initiation factor 2α (eIF2α), phosphorylated eIF2α, activating transcription factor 4 (ATF4), and CCAAT/enhancer-binding protein homologous protein (CHOP) were assessed. P<0.05 was considered to indicate a statistically significant difference. Results DEX preconditioning improved the cardiac function of I/R hearts, reduced myocardial infarction, myocardial apoptosis, and the expression of GRP78, p-PERK, eIF2α, p-eIF2α, ATF4 and CHOP. Conclusions DEX pretreatment reduced myocardial I/R injury by suppressing apoptosis, which was induced by the PERK pathway.


Subject(s)
Animals , Rats , Myocardial Reperfusion Injury/prevention & control , Reperfusion Injury , Myocardial Ischemia , Dexmedetomidine/pharmacology , Myocardial Infarction/prevention & control , Myocardial Infarction/drug therapy , Signal Transduction
16.
Arq. bras. cardiol ; 117(6): 1147-1158, dez. 2021. tab, graf
Article in Portuguese | LILACS | ID: biblio-1350045

ABSTRACT

Resumo Fundamento A doxorrubicina (DOX) é frequentemente usada para tratar muitos tipos de cânceres, apesar da cardiotoxicidade dose-dependente. Como alternativa, o resveratrol é um polifenol que tem demonstrado efeitos cardioprotetores em vários modelos de disfunção cardíaca. Objetivo Este estudo investigou se o tratamento com resveratrol em ratas gestantes protege contra toxicidade induzida por doxorrubicina em cardiomiócitos da ninhada. Métodos Ratas Wistar (n-8) receberam sresveratrol como suplemento alimentar durante a gestação. No nascimento da ninhada, os corações (9-11) foram usados para se obter a cultura primária de cardiomiócitos. A cardiotoxicidade induzida por DOX e os efeitos da suplementação com resveratrol foram avaliados por marcadores de stress oxidativo, tais como oxidação da diclorofluoresceína diacetato, diminuição da atividade de enzimas antioxidantes, e oxidação do teor total de grupos sulfidrila, além da avaliação da viabilidade celular, geração de danos ao DNA, bem como a resposta de reparo aos danos ao DNA. Um valor de p <0,05 foi considerado estatisticamente significativo. Resultados Os cardiomiócitos de neonatos de ratas que receberam suplemento resveratrol apresentaram um aumento (p <0,01) na viabilidade das células, e diminuição (p <0,0001) de células apoptóticas/necróticas após o tratamento com DOX, o que está correlacionado às atividades de enzimas antioxidantes e produção de diclorofluoresceína. Além disso, o resveratrol protegeu os cardiomiócitos de danos ao DNA induzidos por DOX, apresentando uma diminuição (p <0,05) nas quebras de DNA induzidas por stress oxidativo, avaliadas pela atividade de enzimas reparadoras do DNA endonuclease III e formamidopirimidina glicosilase. A suplementação com resveratrol aumentou (p <0,05) a expressão da proteína reparadora Sirt6 nos cardiomiócitos dos filhotes. Conclusão Essa pesquisa indica que a suplementação com resveratrol durante o período gestacional tem um efeito cardioprotetor no coração da ninhada contra a toxicidade induzida por DOX, o que pode se dever a sua função antioxidante, e o aumento na resposta de danos ao DNA.


Abstract Background Doxorubicin (DOX) is frequently used to treat many types of cancers, despite its dose-dependent cardiotoxicity. Alternatively, resveratrol is a polyphenol that has shown useful cardioprotective effects in many heart dysfunction models. Objective This study investigated whether resveratrol treatment in pregnant rats protects against doxorubicin-induced toxicity in offspring cardiomyocytes. Methods Wistar rats (n=8) were supplemented with dietary resveratrol during pregnancy. Upon the offspring's birth, hearts (9-11) were used to obtain the primary culture of cardiomyocytes. DOX-induced cardiotoxicity and the effects of resveratrol supplementation were evaluated by oxidative stress markers, such as dichlorofluorescein diacetate oxidation, decrease in the activity of antioxidant enzymes, and oxidation of total sulfhydryl content, in addition to cell viability evaluation, DNA damage generation, and DNA damage repair response. A value of p<0.05 was considered statistically significant. Results Neonatal cardiomyocytes from resveratrol supplemented rats exhibiting an increase (p<0.01) in cell viability and lower (p<0.0001) apoptotic/necrotic cells after DOX treatment, which correlates with the activities of antioxidant enzymes and dichlorofluorescein production. Moreover, resveratrol protected cardiomyocytes from DOX-induced DNA damage, showing a decrease (p<0.05) in DNA breaks induced by oxidative stress, evaluated by the activity of DNA-repair enzymes endonuclease III and formamidopyrimidine glycosylase. Supplementation with resveratrol increased (p<0.05) the expression of the repair protein Sirt6 in the cardiomyocytes of the pups. Conclusion This research indicates that supplementation with resveratrol during the gestational period has a notable cardioprotective effect on the offspring's heart against DOX-induced toxicity, which may well be due to its antioxidant function, and the increase in the DNA damage repair response.


Subject(s)
Animals , Female , Pregnancy , Rats , Doxorubicin/toxicity , Myocytes, Cardiac , Rats, Wistar , Dietary Supplements , Resveratrol/pharmacology
17.
Arq. bras. cardiol ; 116(5): 970-978, nov. 2021. tab, graf
Article in English, Portuguese | LILACS | ID: biblio-1248893

ABSTRACT

Resumo Fundamento: A vitamina D (VD) tem um importante papel na função cardíaca. No entanto, a vitamina exerce uma curva "dose-resposta" bifásica na fisiopatologia cardiovascular e pode causar efeitos deletérios, mesmo em doses não tóxicas. A VD exerce suas funções celulares ligando-se ao seu receptor. Ainda, a expressão da proteína de interação com a tiorredoxina (TXNIP) é positivamente regulada pela VD. A TXNIP modula diferentes visa de sinalização celular que podem ser importantes para a remodelação cardíaca. Objetivos: Avaliar se a suplementação com VD leva à remodelação cardíaca, e se a TXNIP e a tiorredoxina (Trx) estão associadas com esse processo. Métodos: Duzentos e cinquenta ratos Wistar machos foram alocados em três grupos: controle (C, n=21), sem suplementação com VD; VD3 (n = 22) e VD10 (n=21), suplementados com 3,000 e 10,000 UI de VD/ kg de ração, respectivamente, por dois meses. Os grupos foram comparados por análise de variância (ANOVA) com um fator e teste post hoc de Holm-Sidak (variáveis com distribuição normal), ou pelo teste de Kruskal-Wallis e análise post-hoc de Dunn. O nível de significância para todos os testes foi de 5%. Resultados: A expressão de TXNIP foi mais alta e a atividade do Trx foi mais baixa no grupo VD10. Os animais que receberam suplementação com VD apresentaram aumento de hidroperóxido lipídico e diminuição de superóxido dismutase e glutationa peroxidase. A proteína Bcl-2 foi mais baixa no grupo VD10. Observou-se uma diminuição na β-oxidação de ácidos graxos, no ciclo do ácido tricarboxílico, na cadeia transportadora de elétrons, e um aumento na via glicolítica. Conclusão: A suplementação com VD levou à remodelação cardíaca e esse processo pode ser modulado por TXNIP e Trx, e consequentemente por estresse oxidativo.


Abstract Background: Vitamin D (VD) has been shown to play an important role in cardiac function. However, this vitamin exerts a biphasic "dose response" curve in cardiovascular pathophysiology and may cause deleterious effects, even in non-toxic doses. VD exerts its cellular functions by binding to VD receptor. Additionally, it was identified that the thioredoxin-interacting protein (TXNIP) expression is positively regulated by VD. TXNIP modulate different cell signaling pathways that may be important for cardiac remodeling. Objective: To evaluate whether VD supplementation lead to cardiac remodeling and if TXNIP and thioredoxin (Trx) proteins are associated with the process. Methods: A total of 250 Male Wistar rats were allocated into three groups: control (C, n=21), with no VD supplementation; VD3 (n = 22) and VD10 (n=21), supplemented with 3,000 and 10,000 IU of VD/ kg of chow respectively, for two months. The groups were compared by one-way analysis of variance (ANOVA) and Holm-Sidak post hoc analysis, (variables with normal distribution), or by Kruskal-Wallis test and Dunn's test post hoc analysis. The significance level for all tests was 5%. Results: TXNIP protein expression was higher and Trx activity was lower in VD10. The animals supplemented with VD showed increased lipid hydroperoxide and decreased superoxide dismutase and glutathione peroxidase. The protein Bcl-2 was lower in VD10. There was a decrease in fatty acid β-oxidation, tricarboxylic acid cycle and electron transport chain with shift to increase in glycolytic pathway. Conclusion: VD supplementation led to cardiac remodeling and this process may be modulated by TXNIP and Trx proteins and consequently oxidative stress.


Subject(s)
Animals , Male , Rats , Thioredoxins/metabolism , Ventricular Remodeling , Vitamin D , Rats, Wistar , Oxidative Stress , Cell Cycle Proteins , Dietary Supplements
18.
Int. braz. j. urol ; 47(5): 1020-1029, Sept.-Oct. 2021. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1286813

ABSTRACT

ABSTRACT Early weaning can predispose the offspring to greater risk of developing chronic diseases in adulthood. It is believed that the consumption of functional foods is able to prevent these effects. The aim of this study is to evaluate the effects of maternal and postnatal cocoa powder supplementation on body mass, metabolism, and morphology of the prostate of early weaned Wistar rats. The animals were divided into four experimental groups according to lactation time (21 or 18 days, n=6, each) as follows: control group (C), cocoa control group (CCa), early weaning group (EW), and cocoa early weaning group (EWCa). The animals were euthanized at 90 days of age. Serum biochemical analysis and prostate histomorphometric evaluation were performed. The animals supplemented with cocoa powder were heavier than their respective controls (p <0.05), although with no difference in food intake among the groups. Likewise, these same groups showed a reduction in the serum glucose in relation to C and EW groups (p <0.0001). With respect to the prostate, there was no difference in smooth muscle and lumen area densities, while the EW group had a lower epithelial height and a higher percentage of mast cells than the C group (p <0.05). On the other hand, the EWCa group managed to reverse these parameters, leveling with the controls. Early weaning resulted in hyperglycemia and important morphological changes in the prostate. In contrast, dietary supplementation with cocoa powder attenuated these effects on the metabolism and prostatic histoarchitecture, proving to be a good nutritional treatment strategy.

19.
Electron. j. biotechnol ; 52: 52-58, July. 2021. tab, ilus
Article in English | LILACS | ID: biblio-1283505

ABSTRACT

BACKGROUND: Osteoporosis attacks approximately 10% of the population worldwide. Sika Deer (Cervus nippon), one of China's precious traditional medicinal animals, has been widely recorded in ancient Chinese medical books and claimed for centuries to have numerous medical benefits including bone strengthening. This study aimed to find the use of Sika Deer bone in treating osteoporosis according to traditional records and to investigate the protective effect of Sika Deer bone polypeptide extract on glucocorticoidinduced osteoporosis (GIOP) in rats. RESULTS: Sika Deer bone polypeptide extract could increase serum Ca2+ and BGP, decrease serum P3+, ALP, PTH, and CT, but had no effect on serum NO in rats with GIOP. The immunohistochemical iNOS results of the rats' distal femur were negative in each group. Besides the model group, the eNOS color reaction in osteoblasts was strongly positive in the other three groups. CONCLUSIONS: Sika Deer bone polypeptide extract can improve pathological changes in the microstructure and stimulate the expression of eNOS in osteoblasts. The protective effect on bone might be mediated by eNOS-dependent NO generation.


Subject(s)
Animals , Male , Rats , Osteoporosis/prevention & control , Peptides/pharmacology , Bone and Bones/metabolism , Deer , Osteoblasts , Dexamethasone , Rats, Wistar , Nitric Oxide Synthase Type III/drug effects
20.
Rev. bras. cir. plást ; 36(3): 257-262, jul.-set. 2021. tab, graf
Article in Portuguese | LILACS-Express | LILACS | ID: biblio-1365564

ABSTRACT

RESUMO Introdução: O controle da absorção de proteínas é necessário para a definição das propriedades dos biomateriais e de seus usos específicos. O plasma sanguíneo contém diversas proteínas diferentes, dentre elas o fibrinogênio, que apresenta importante papel na adesão celular e nos resultados de biocompatibilidade em implantes. Os objetivos deste estudo foram avaliar laboratorialmente as ratas submetidas à colocação de mini-implantes de silicone nanotexturizados e revestidos por espuma de poliuretano a partir da aferição do fibrinogênio sérico e mensuração da proteína plasmática. Métodos: Foram utilizadas 60 ratas albinas, divididas em dois grupos de 30 animais para cada tipo de mini-implante de silicone (nanotexturizado e espuma de poliuretano) e subdivididas em 3 subgrupos, conforme o tempo de eutanásia dos animais (30, 60 e 90 dias). Os mini-implantes foram inseridos no dorso dos animais abaixo do Panniculus carnosus. No momento das eutanásias, amostras de sangue foram obtidas por punção cardíaca. Utilizou-se a técnica de precipitação térmica para determinação das proteínas plasmáticas total e sérica, e o valor do fibrinogênio foi obtido mediante a diferença entre estas duas últimas. Resultados: Quando comparados os grupos entre si, observou-se que o grupo nanotexturizado apresentou uma maior quantidade de fibrinogênio e da proteína plasmática no subgrupo de 90 dias, com significância estatística (p=0,004). Ao comparar os subgrupos entre si, em ambos os grupos, evidenciou-se uma diferença significativa (p<0,001). Conclusão: Os mini-implantes nanotexturizados mostraram uma menor absorção de proteínas em relação aos implantes revestidos pela espuma de poliuretano, no subgrupo de 90 dias.


ABSTRACT Introduction: The control of protein absorption is necessary to define biomaterials' properties and their specific uses. Blood plasma contains several different proteins, including fibrinogen, which plays an important role in cell adhesion and biocompatibility results in implants. This study's objectives were to evaluate in the laboratory rats subjected to the placement of nano-textured silicone mini-implants and polyurethane foam-coated mini-implants based on the measurement of serum fibrinogen and plasma proteins. Methods: Sixty albino rats were used, divided into two groups of 30 animals for each type of silicone mini-implant (nanotextured and polyurethane foam) and subdivided into three subgroups, according to the animals' euthanasia time (30, 60 and 90 days). The mini-implants were inserted in the animals' backs below the Panniculus carnosus. At the time of euthanasia, blood samples were obtained by cardiac puncture. The thermal precipitation technique was used to determine total and serum plasma proteins, and the difference between the latter two obtained the fibrinogen value. Results: When the groups were compared, it was observed that the nanotextured group presented a higher amount of fibrinogen and plasma protein in the 90-day subgroup, with statistical significance (p=0.004). When comparing the subgroups among themselves, a significant difference was evidenced (p<0.001). Conclusion: The nanotextured mini-implants showed a lower protein absorption concerning polyurethane foam-coated implants in the 90-day subgroup.

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