S-allylcysteine prevents cisplatin-induced nephrotoxicity and oxidative stress.
OBJECTIVE
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.


RESULTS
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.
Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico (UNAM), DF, Mexico.
Tania
T
Gómez-Sierra
Eduardo
E
Molina-Jijón
Edilia
E
Tapia
Rogelio
R
Hernández-Pando
Wylly Ramsés
WR
García-Niño
Perla D
PD
Maldonado
José Luis
JL
Reyes
Diana
D
Barrera-Oviedo
Ismael
I
Torres
José
J
Pedraza-Chaverri
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D002374:Catalase / Q000378:metabolism; D002945:Cisplatin / Q000009:adverse effects* / Q000627:therapeutic use; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005737:Garlic / Q000737:chemistry*; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007674:Kidney Diseases / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D064546:Protein Kinase C beta / Q000378:metabolism; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
D000970:Antineoplastic Agents; D000975:Antioxidants; D008562:Membrane Glycoproteins; D051267:NF-E2-Related Factor 2; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; C065299:S-allylcysteine; D002374:Catalase; D005979:Glutathione Peroxidase; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D005980:Glutathione Reductase; D064546:Protein Kinase C beta; D003545:Cysteine; D002945:Cisplatin
S-allylcysteine; cisplatin; nephrotoxicity; nuclear factor-erythroid 2-related factor-2; oxidative stress