Antioxidant S-allylcysteine prevents gentamicin-induced oxidative stress and renal damage.
Acute renal failure (ARF) is a major complication of gentamicin (GM) treatment, which is effective against gram-negative infections. Since experimental evidence suggests a role of reactive oxygen species (ROS) in GM-induced ARF, in this work we studied the effect of a garlic-derived compound, S-allylcysteine (SAC), which is a free radical scavenger, on GM-induced nephrotoxicity. In rats treated with GM (70 mg/kg/12 h/4 days/s.c.), ARF was evident by the: (i) decrease in creatinine clearance and increase in blood urea nitrogen, (ii) decrease in blood glutathione peroxidase (GPx) activity and increase in urinary excretion of N-acetyl-beta-D-glucosaminidase and total protein, and (iii) necrosis of proximal tubular cells. These alterations were prevented by SAC treatment (250 mg/kg/i.p. 24 h before the first dose of GM and 125 mg/kg/12 h/4 days along GM-treatment). Furthermore, SAC prevented the GM-induced oxidative stress (protein carbonyl groups) and the decrease in manganese superoxide dismutase (Mn-SOD), GPx, and glutathione reductase (GR) activities in renal cortex. In conclusion, SAC ameliorates the GM-induced ARF by a mechanism related, at least in part, to its ability to decrease oxidative stress and to preserve antioxidant enzymes activity in renal cortex.
Maldonado
Perla D
PD
Department of Biology, Universidad Nocional Autonoma de Mexico, Mexico D.F., Mexico.
Barrera
Diana
D
Rivero
Isabel
I
Mata
Rachel
R
Medina-Campos
Omar N
ON
Hernández-Pando
Rogelio
R
Pedraza-Chaverrí
José
J
D000118:Acetylglucosaminidase / Q000652:urine; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001835:Body Weight; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D016166:Free Radical Scavengers; D005609:Free Radicals; D005737:Garlic; D005839:Gentamicins / Q000009:adverse effects* / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000097:blood / Q000378:metabolism; D007668:Kidney / Q000293:injuries / Q000473:pathology*; D007672:Kidney Cortex / Q000473:pathology; D007684:Kidney Tubules / Q000473:pathology; D008297:Male; D009336:Necrosis; D018384:Oxidative Stress; D010936:Plant Extracts; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species; D013997:Time Factors
D000900:Anti-Bacterial Agents; D000975:Antioxidants; D016166:Free Radical Scavengers; D005609:Free Radicals; D005839:Gentamicins; D010936:Plant Extracts; D017382:Reactive Oxygen Species; C065299:S-allylcysteine; D005979:Glutathione Peroxidase; D000118:Acetylglucosaminidase; D003545:Cysteine