Vitamin C protects against in vitro cytotoxicity of cypermethrin in rat hepatocytes.
The objective of this study was to investigate the effect of ascorbic acid (AA) on the in vitro cytotoxicity of cypermethrin (CM), and on glutathione (GSH) metabolism in rat hepatocytes. In vitro cell viability, lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) leakage were measured, as indicators of hepatic damage, at 1, 15 and 30 min of exposure to CM. Glutathione and the activities of glutathione-S-transferase (GST) and gamma glutamyl transpeptidase (gamma-GT) were also measured. CM hepatotoxicity increased in a time and dose-dependent manner. In the presence of 30 microM CM, ALT and AST also increased 49 and 130% (P < 0.05), respectively, indicating metabolic hepatocyte damage. AA (1 mM) was capable to preserve 100% of cell integrity and modulated ALT and AST. Furthermore, CM induced a 27% reduction in the endogenous antioxidant GSH, and increased 203% GST and 283% gamma-GT (P < 0.05), indicating an oxidative insult. The presence of AA showed chemopreventive capacity against CM, recovering 60% of GSH and a 54% decrease in gamma-GT activity. These results suggest that AA in a 1:33 (CM:AA) ratio can modulate up to 90% of the damage caused to the cells by CM. It also demonstrates that AA can act as a primary antioxidant and hepatoprotector in rat hepatocytes.
Grajeda-Cota
Patricia
P
Research Center for Food and Development (CIAD), Hermosillo, Sonora, Mexico.
Ramírez-Mares
Marco Vinicio
MV
González de Mejía
Elvira
E
D000410:Alanine Transaminase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology* / Q000502:physiology; D001219:Aspartate Aminotransferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects* / Q000502:physiology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005978:Glutathione / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors / Q000502:physiology; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D007770:L-Lactate Dehydrogenase; D008099:Liver / Q000166:cytology / Q000187:drug effects; D008297:Male; D010477:Perfusion; D011722:Pyrethrins / Q000009:adverse effects* / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D011722:Pyrethrins; C017160:cypermethrin; D007770:L-Lactate Dehydrogenase; D005723:gamma-Glutamyltransferase; D005982:Glutathione Transferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione; D001205:Ascorbic Acid; D004121:Dimethyl Sulfoxide