Dose-dependent protection by lipoic acid against cisplatin-induced nephrotoxicity in rats: antioxidant defense system.

This study was designed to investigate the role of graded doses of lipoic acid pretreatment against cisplatin-induced nephrotoxicity. Male Wistar rats were divided into six groups and treated as follows: 1) vehicle (saline) control; 2) cisplatin (16 mg/kg, intraperitoneally); 3) lipoic acid (100 mg/kg, intraperitoneally); 4) cisplatin plus lipoic acid (25 mg/kg); 5) cisplatin plus lipoic acid (50 mg/kg) and 6) cisplatin plus lipoic acid (100 mg/kg). Rats were sacrificed three days after treatment, and plasma as well as kidneys were isolated and analyzed. Plasma creatinine increased (677% of control) following cisplatin administration alone which was decreased by lipoic acid in a dose-dependent manner. Cisplatin-treated rats showed a depletion of renal glutathione (GSH), increased oxidized GSH and decreased GSH/GSH oxidized ratio (62%, 166% and 62% of control), respectively which were restored with lipoic acid pretreatment. Renal superoxide dismutase, catalase, glutathione peroxidase (GSH peroxidase) and glutathione reductase activities decreased (62%, 75%, 62% and 80% of control), respectively, and malondialdehyde content increased (204% of control) following cisplatin administration, which were restored with increasing doses of lipoic acid. The renal platinum concentration increased following cisplatin administration, which was possibly decreased by chelation with lipoic acid. The data suggest that the graded doses of lipoic acid effectively prevented a decrease in renal antioxidant defense system and prevented an increase in lipid peroxidation, platinum content and plasma creatinine concentrations in a dose-dependent manner.

Protection by ebselen against cisplatin-induced nephrotoxicity: antioxidant system.

This study was designed to investigate the cisplatin-induced alteration in renal antioxidant system and the nephroprotection with ebselen. Male Wistar rats were injected with (1) vehicle control; (2) cisplatin; (3) ebselen; and (4) cisplatin plus ebselen. Rats were sacrificed three days post-treatment and plasma as well as kidney were isolated and analyzed. Plasma creatinine increased 598% following cisplatin administration alone which decreased by 158% with ebselen pretreatment. Cisplatin-treated rats showed a depletion of renal glutathione (GSH) levels (52% of control), while cisplatin plus ebselen injected rats had GSH values close to the controls. Antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities decreased 38, 75 and 62% of control, respectively, and malondialdehyde (MDA) levels increased 174% of control following cisplatin administration, which were restored to control levels after ebselen treatment. The renal platinum level did not significantly change with ebselen pretreatment. This study suggests that the protection offered by ebselen against cisplatin-induced nephrotoxicity is partly related to the sparing of antioxidant system.

Interaction of exercise and ethanol on antioxidant enzymes in brain regions of the rat.

This study investigates the effect of ethanol ingestion on antioxidant enzymes (AOE) and lipid peroxidation (malondialdehyde, (MDA) in different brain regions of the rat after acute exercise. Acute exercise (100% VO2max) significantly increased glutathione peroxidase (GSH-Px) activity and decreased glutathione reductase (GR) activity in the cerebral cortex. Acute exercise significantly increased MDA level in the corpus striatum. Ethanol (20%) (1.6 g/kg, PO) significantly increased MDA level in the cerebral cortex. Ethanol also significantly increased superoxide dismutase (SOD) activity in the cortex and catalase (CAT), GSH-Px, and GR activities in the corpus striatum. Ethanol significantly augmented CAT activity in the medulla and GSH-Px activity in the hypothalamus. However, CAT activity significantly decreased in the hypothalamus after ethanol ingestion. The combination significantly increased GSH-Px activity in the hypothalamus, SOD activity in the cortex, GR activity in the striatum, and MDA level in the medulla. In conclusion, the cerebral cortex, striatum medulla, and hypothalamus reacted differentially in response to ethanol as well as to acute exercise-induced oxidative stress whereas the combination moderated the changes in AOE activity in specific brain regions.