Nicotinamide prevents N-methyl-N-nitrosourea-induced photoreceptor cell apoptosis in Sprague-Dawley rats and C57BL mice.
In previous studies, it was found that a single systemic administration of N-methyl-N-nitrosourea (MNU) to rats and mice resulted in the retinal degeneration in all treated animals over a 7 day period. Retinal degeneration was due to photoreceptor cell apoptosis that was identical to the apoptosis seen in human retinitis pigmentosa (RP). In the present study, nicotinamide (NAM), a water-soluble B-group vitamin (vitamin B(3)), suppressed photoreceptor cell loss in a dose-dependent manner when administered immediately after MNU treatment. In rats, a dose of NAM >or=25 mg kg(-1) completely suppressed photoreceptor cell loss, and 10 mg kg(-1) partially suppressed photoreceptor cell loss. In mice, doses of 1000 and >or=100 mg kg(-1) were needed for complete and partial suppression, respectively. Thus, rats were more responsive to NAM than mice. The retinoprotective effect of 1000 mg kg(-1) NAM lasted throughout the long-term (35 days) observation period, with no apparent toxicity. Also, in rats, 1000 mg kg(-1) NAM completely suppressed photoreceptor cell loss when administered up to 4 hr after MNU treatment, and partially suppressed photoreceptor cell loss when administered 6 hr after MNU treatment. In mice, administration of NAM 2-6 hr after MNU resulted in partial suppression. NAM did not reduce levels of 7-methyldeoxyguanosine DNA adduct, but did reduce photoreceptor cell apoptosis. Although the mechanism of action underlying this retinoprotection remains to be clarified, NAM may be a potential therapeutic agent for the treatment of retinal degeneration.
Kiuchi
Katsuji
K
Department of Pathology, Kansai Medical University, Moriguchi, Osaka 570-8506, Japan.
Yoshizawa
Katsuhiko
K
Shikata
Nobuaki
N
Matsumura
Miyo
M
Tsubura
Airo
A
D000477:Alkylating Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D020287:In Situ Nick-End Labeling; D008770:Methylnitrosourea / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009536:Niacinamide / Q000627:therapeutic use*; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects; D012174:Retinitis Pigmentosa / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*
D000477:Alkylating Agents; D009536:Niacinamide; D008770:Methylnitrosourea