title: Niacin deficiency causes oxidative stress in rat bone marrow cells but not through decreased NADPH or glutathione status.
abstract: Niacin (vitamin B(3)), in the form of NADPH, is required for the regeneration of glutathione (GSH), which is the substrate of GSH peroxidase. In this study, we examined the effect of dietary niacin deficiency on protein and DNA oxidation in bone marrow cells of Long-Evans rats. Western blotting was used to measure 2,4-dinitrophenylhydrazine-reactive protein carbonyl products, and the Biotrin OxyDNA method was used to measure 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG). The levels of both protein carbonyls and 8-oxodG were increased by 50% in niacin-deficient bone marrow cells. To examine whether this oxidant damage involves altered metabolism of pyridine nucleotides and glutathione, both oxidized and reduced forms of pyridine nucleotides (NAD(+), NADH, NADP(+), NADPH) and glutathione (GSSG and GSH) were quantified in total and nucleated bone marrow cells. NAD and NADP(+) levels were decreased 80% and 22%, respectively, by niacin deficiency. NADPH and GSH were not depleted by niacin deficiency, showing that oxidant injury was not due directly to impairment of this pathway. Oxidative stress, of uncertain etiology, may play a role in the observed genomic instability and sensitivity to leukemogenesis in bone marrow cells during niacin deficiency.
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada N1G 2W1.
authors.forename: Kitty
authors.initials: K
authors.lastname: Tang
authors.forename: Heidi
authors.initials: H
authors.lastname: Sham
authors.forename: Evon
authors.initials: E
authors.lastname: Hui
authors.forename: James B
authors.initials: JB
authors.lastname: Kirkland
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism*; D002244:Carbon / Q000737:chemistry; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000494:pharmacology; D005434:Flow Cytometry; D005978:Glutathione / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D009249:NADP / Q000378:metabolism*; D009525:Niacin / Q000172:deficiency*; D018384:Oxidative Stress; D010659:Phenylhydrazines / Q000494:pharmacology; D011725:Pyridines / Q000737:chemistry; D051381:Rats; D020318:Rats, Long-Evans
chemical_list: D010659:Phenylhydrazines; D011725:Pyridines; C004787:2,4-dinitrophenylhydrazine; D009525:Niacin; D009249:NADP; D002244:Carbon; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D005978:Glutathione