Efeitos da leucina no estresse oxidativo hepático e renal em ratos tratados com doxorrubicina

Abstract

Hepatic and renal toxicity is one of the side effects of doxorubicin used in the antineoplastic treatment. The aim of this study was to determine if leucine supplementation in the diet of Wistar rats treated with doxorubicin has protective hepatic and renal action evidenced by the reduction of oxidative stress. The experiment included 36 rats distributed in four groups, with 8 Control, 8 LEUcina, 10 DOXorubicin and 10 DOX + LEU. Animals from the DOX and DOX + LEU groups were treated with intraperitoneal injections of doxorubicin for two weeks, three times a week, at a cumulative dose of 7.5 mg / kg. The animals of groups C and LEU received intraperitoneal volume of saline daily, similar to that administered with doxorubicin. The LEU and DOX-LEU groups received the amino acid leucine throughout the study plus 5% added to the basal diet. Hepatic and renal tissue oxidative stress was evaluated by the dosages of the antioxidant enzymes catalase, superoxide dismutase (SOD), glutathione peroxidase (Gpx), glutathione reductase (GR) and also reduced levels of glutathione (GSH) and glucose-6-phosphate dehydrogenase (G6PDH); the oxidizing activity was measured by lipid peroxidation (thiobarbituric acid-TBARS). The hepatic collagen content was evaluated in histological analysis using picrosirius red staining; for analysis of the hepatic and renal tissues the Gomori trichrome was used. The results were presented as mean ± standard error of the mean (EPM), using GraphPad Prism software version 5.0. The results were compared by the Student's t-Test or the analysis of variance (ANOVA), as appropriate. To verify the detected differences between the groups, the Tukey test was used. Differences were considered significant when p <0.05. The results showed that, in the liver, the DOX group compared to the LEU presented higher antioxidant activity of SOD, catalase and Gpx, and GSH levels and lower levels of lipid peroxidation and collagen deposition. The group DOX + LEU compared to the LEU group also presented lower levels of lipid peroxidation and collagen deposition, and finally, the DOX + LEU group, when compared to the DOX group, presented lower oxidant activity and lower antioxidant activity of SOD, catalase, Gpx and GSH. The renal analyzes showed an increase in oxidative stress in the LEU group evidenced by the increase in GR. All experimental groups had a reduction in the total number of glomeruli in relation to the control. There was no change in collagen deposition. It was concluded that the addition of 5% leucine to the diet administered to doxorubicin treated rats showed a hepatoprotective effect. The hypothesis of leucine nephroprotective effect evidenced by the reduction of oxidative stress was not demonstrated.