Premium
Preventing cell death induced by carbonyl stress, oxidative stress or mitochondrial toxins with vitamin B anti‐AGE agents
Author(s) -
Mehta Rhea,
Shangari Nandita,
O'Brien Peter J.
Publication year - 2008
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.200600190
Subject(s) - oxidative stress , lipid peroxidation , chemistry , pyridoxal , programmed cell death , glycation , biochemistry , cytotoxicity , reactive oxygen species , thiamine pyrophosphate , pharmacology , vitamin e , antioxidant , apoptosis , biology , in vitro , cofactor , receptor , phosphate , enzyme
Carbonyls generated by autoxidation of carbohydrates or lipid peroxidation have been implicated in advanced glycation end product (AGE) formation in tissues adversely affected by diabetes complications. Tissue AGE and associated pathology have been decreased by vitamin B 1 /B 6 in trials involving diabetic animal models. To understand the molecular cytoprotective mechanisms involved, the effects of B 1 /B 6 vitamers against cytotoxicity induced by AGE/advanced lipid end product (ALE) carbonyl precursors (glyoxal/acrolein) have been compared to cytotoxicity induced by oxidative stress (hydroperoxide) or mitochondrial toxins (cyanide/copper). Thiamin was found to be best at preventing cell death induced by carbonyl stress and mitochondrial toxins but not oxidative stress cell death suggesting that thiamin pyrophosphate restored pyruvate and α‐ketoglutarate dehydrogenases inhibited by mitochondrial toxicity. However, B 6 vitamers were most effective at preventing oxidative stress or lipid peroxidation cytotoxicity suggesting that pyridoxal or pyridoxal phosphate were antioxidants and/or Fe/Cu chelators. A therapeutic vitamin cocktail could provide maximal prevention against carbonyl stress toxicity associated with diabetic complications.