Protective effect of diallyl sulfide on oxidative stress and nephrotoxicity induced by gentamicin in rats.
Gentamicin (GM) is an antibiotic whose clinical use is limited by its nephrotoxicity. Experimental evidences suggest a role of reactive oxygen species in GM-induced nephrotoxicity. In this work we explored the effect of diallyl sulfide (DAS), a garlic-derived compound with antioxidant properties, on GM-induced nephrotoxicity. Four groups of rats were studied: (1) Control, treated intragastrically with olive oil as a vehicle, (2) GM, treated subcutaneously with GM (125 mg/kg/day for 4 days), (3) DAS, treated intragastrically with DAS (50 mg/kg/day for 4 days), and (4) GM + DAS. Nephrotoxicity was made evident by: (1) the increase in creatinine and blood urea nitrogen in serum, (2) the increase in urinary excretion of N-acetyl-beta-D-glucosaminidase and total protein, and (3) necrosis of proximal tubular cells. These functional and structural alterations were prevented or ameliorated by DAS treatment. In addition, GM increased levels of renal oxidative stress markers nitrotyrosine and protein carbonyl groups which were also ameliorated by DAS in GM + DAS group. The mechanism by which DAS has a protective effect on GM-induced nephrotoxicity may be related, at least in part, to the decrease in oxidative stress in renal cortex.
Pedraza-Chaverrí
José
J
Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico, Mexico. pedraza@servidor.unam.mx
Maldonado
Perla D
PD
Barrera
Diana
D
Cerón
Alejandra
A
Medina-Campos
Omar N
ON
Hernández-Pando
Rogelio
R
D000118:Acetylglucosaminidase / Q000378:metabolism; D000498:Allyl Compounds / Q000737:chemistry*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D001806:Blood Urea Nitrogen; D001835:Body Weight; D002244:Carbon / Q000737:chemistry; D003404:Creatinine / Q000097:blood / Q000378:metabolism; D005839:Gentamicins / Q000494:pharmacology*; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects; D007672:Kidney Cortex / Q000378:metabolism; D007684:Kidney Tubules / Q000166:cytology; D008297:Male; D009336:Necrosis; D000069463:Olive Oil; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D010938:Plant Oils; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species; D013440:Sulfides / Q000737:chemistry*; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000737:chemistry
D000498:Allyl Compounds; D000900:Anti-Bacterial Agents; D000975:Antioxidants; D005839:Gentamicins; D000069463:Olive Oil; D010938:Plant Oils; D017382:Reactive Oxygen Species; D013440:Sulfides; C002744:3-nitrotyrosine; D014443:Tyrosine; C038491:allyl sulfide; D002244:Carbon; D003404:Creatinine; D000118:Acetylglucosaminidase; D010100:Oxygen