S-allylmercaptocysteine scavenges hydroxyl radical and singlet oxygen in vitro and attenuates gentamicin-induced oxidative and nitrosative stress and renal damage in vivo.
BACKGROUND
Oxidative and nitrosative stress have been involved in gentamicin-induced nephrotoxicity. The purpose of this work was to study the effect of S-allylmercaptocysteine, a garlic derived compound, on gentamicin-induced oxidative and nitrosative stress and nephrotoxicity. In addition, the in vitro reactive oxygen species scavenging properties of S-allylmercaptocysteine were studied.


RESULTS
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-beta-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).


CONCLUSIONS
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.
Pedraza-Chaverrí
José
J
Departamento de Biología, Universidad Nacional Autónoma de México (UNAM), Ciudad Universitaria, 04510, México, D,F, México. pedraza@servidor.unam.mx
Barrera
Diana
D
Maldonado
Perla D
PD
Chirino
Yolanda I
YI
Macías-Ruvalcaba
Norma A
NA
Medina-Campos
Omar N
ON
Castro
Leticia
L
Salcedo
Marcos I
MI
Hernández-Pando
Rogelio
R
D000447:Aldehydes / Q000276:immunology / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001835:Body Weight / Q000502:physiology; D002264:Carboxylic Acids / Q000378:metabolism; D003545:Cysteine / Q000031:analogs & derivatives* / Q000502:physiology*; D004140:Dinitrophenols / Q000276:immunology / Q000378:metabolism; D002149:Energy Intake / Q000502:physiology; D016166:Free Radical Scavengers / Q000378:metabolism*; D005839:Gentamicins / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D017665:Hydroxyl Radical / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D007672:Kidney Cortex / Q000737:chemistry / Q000201:enzymology / Q000473:pathology; D007674:Kidney Diseases / Q000097:blood / Q000209:etiology* / Q000652:urine; D007678:Kidney Glomerulus / Q000098:blood supply / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000098:blood supply / Q000473:pathology; D008297:Male; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000276:immunology / Q000378:metabolism; D014556:Urine / Q000502:physiology
D000447:Aldehydes; D015415:Biomarkers; D002264:Carboxylic Acids; D004140:Dinitrophenols; D016166:Free Radical Scavengers; D005839:Gentamicins; D011506:Proteins; D017382:Reactive Oxygen Species; C086300:S-allylmercaptocysteine; D017665:Hydroxyl Radical; C002744:3-nitrotyrosine; D014443:Tyrosine; C027576:4-hydroxy-2-nonenal; D003545:Cysteine