S-allylmercaptocysteine scavenges hydroxyl radical and singlet oxygen in vitro and attenuates gentamicin-induced oxidative and nitrosative stress and renal damage in vivo

S-allylmercaptocysteine was able to scavenge hydroxyl radicals and singlet oxygen in vitro. In rats treated with gentamicin (70 mg/Kg body weight, subcutaneously, every 12 h, for 4 days), renal oxidative stress was made evident by the increase in protein carbonyl content and 4-hydroxy-2-nonenal, and the nitrosative stress was made evident by the increase in 3-nitrotyrosine. In addition, gentamicin-induced nephrotoxicity was evident by the: (1) decrease in creatinine clearance and in activity of circulating glutathione peroxidase, and (2) increase in urinary excretion of N-acetyl-β-D-glucosaminidase, and (3) necrosis of proximal tubular cells. Gentamicin-induced oxidative and nitrosative stress and nephrotoxicity were attenuated by S-allylmercaptocysteine treatment (100 mg/Kg body weight, intragastrically, 24 h before the first dose of gentamicin and 50 mg/Kg body weight, intragastrically, every 12 h, for 4 days along gentamicin-treatment).In conclusion, S-allylmercaptocysteine is able to scavenge hydroxyl radicals and singlet oxygen in vitro and to ameliorate the gentamicin-induced nephrotoxicity and oxidative and nitrosative stress in vivo.Reactive oxygen species (ROS) and reactive nitrogen species (RNS) have been implicated in several renal diseases [1-8] including the renal damage induced by the antibiotic gentamicin (GM) [9-19]. GM induces superoxide anion (O2-), hydrogen peroxide (H2O2), and hydroxyl radical (HO) production from renal mitochondria [13,14]. In addition, H2O2 generation [15], lipoperoxidation [16,17], and the content of nitrotyrosine [10-12], and protein carbonyl [10,18] are increased and that of reduced glutathione is diminished [18] in renal cortex from GM-treated rats. Moreover, the administration of several compounds with antioxidant properties, ROS scavengers, and/or antioxidant enzymes are able to ameliorate the severity of GM-induced renal damage [9,10,16-19]. In addition, the kidneys from GM-treated rats are more vulnerable to ROS because