Effects of folate on arsenic toxicity in Chang human hepatocytes: involvement of folate antioxidant properties.
We investigated the effects and modes of action of the nutritional factor folate on arsenic-induced toxicity in Chang human hepatocytes. Cells were cultured in folate-deficient medium, normal folate medium or folate-supplemented medium for 1h and then co-treated with or without 20-microM sodium arsenite (NaAsO(2)) for 24h. The results showed that folate deficiency significantly aggravated the NaAsO(2)-induced apoptotic progression [evidenced by phosphatidylserine externalization, cleavage of caspase-3 and poly (ADP-ribose) polymerase (PARP), collapse of mitochondrial potential, and release of cytochrome c from the mitochondria] and decrease of cell viability. Folate supplementation significantly attenuated all the above mentioned NaAsO(2)-induced effects except phosphatidylserine externalization. The NaAsO(2)-induced generation of intracellular reactive oxygen species and malondialdehyde was aggravated, to some extent, by folate deficiency, but these phenomena were significantly suppressed by folate supplementation. In contrast, NaAsO(2)-induced elevation of reduced glutathione levels was significantly suppressed by folate deficiency, but significantly enhanced by folate supplementation. In addition, folate deficiency significantly decreased the arsenic methylation capacity of the hepatocytes, but had no effects on cellular retention of arsenic. Folate supplementation had no significant effect on cellular retention or methylation of arsenic. These results indicate that folate deficiency aggravates arsenic-induced toxicity and apoptosis, while folate supplementation attenuates these effects. Folate, which plays a role in arsenic metabolism, also exerts its effect on arsenic toxicity at least partly because of its antioxidant property.
Xu
Yuanyuan
Y
Department of Occupational and Environmental Health, College of Public Health, China Medical University, No. 92 Bei Er Road, Shenyang, Liaoning, PR China.
Wang
Huihui
H
Wang
Yi
Y
Zheng
Yi
Y
Sun
Guifan
G
D017209:Apoptosis / Q000187:drug effects; D001151:Arsenic / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005492:Folic Acid / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects*; D006801:Humans
D005492:Folic Acid; D001151:Arsenic