Objectives: Cisplatin (CP) is an antineoplastic agent that induces nephrotoxicity and oxidative stress. S-allylcysteine (SAC) is a garlic-derived antioxidant. This study aims to explore whether SAC protects against CP-induced nephrotoxicity in rats.
Methods: In the first stage, the SAC protective dose was determined by measuring renal damage and the oxidative stress markers malondialdehyde, oxidized proteins and glutathione in rats injected with CP. In the second stage, the effect of a single dose of SAC on the expression of nuclear factor-erythroid 2-related factor-2 (Nrf2), protein kinase C beta 2 (PKCβ2) and nicotinamide adenine dinucleotide phosphate oxidase subunits (p47(phox) and gp91(phox) ) was studied. In addition, the effect of SAC on oxidative stress markers and on the activity of catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) in isolated proximal and distal tubules were evaluated.
Key findings: SAC (25 mg/kg) prevented the CP-induced renal damage and attenuated CP-induced decrease in Nrf2 levels and increase in PKCβ2, p47(phox) and gp91(phox) expression in renal cortex and oxidative stress and decrease in the activity of CAT, GPx and GR in proximal and distal tubules.
Conclusions: These data suggest that SAC provides renoprotection by attenuating CP-induced oxidative stress and decrease in the activity of CAT, GPx and GR.
Keywords: S-allylcysteine; cisplatin; nephrotoxicity; nuclear factor-erythroid 2-related factor-2; oxidative stress.
© 2014 Royal Pharmaceutical Society.