Preventing cell death induced by carbonyl stress, oxidative stress or mitochondrial toxins with vitamin B anti-age agents.
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 alphaketoglutarate 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.
Mol Nutr Food Res. 2008 Mar;52(3):379-85