Neuroprotective Effects of Nicotinamide (Vitamin B3) on Neurodegeneration in Diabetic Rat Retinas

Abstract

The loss of inner retinal neurons is an initial event in diabetic retinopathy. In diabetic retinas, oxidative stress is increased, which could lead to increased oxidative DNA damage. Nicotinamide is a precursor to nicotinamide adenine dinucleotide, which contributes to the DNA damage response. We investigated whether nicotinamide plays a neuroprotective role in diabetic retinal neurodegeneration in terms of DNA repair. Male Sprague Dawley rats with streptozotocin-induced diabetes were orally administered nicotinamide (500 mg/kg/day) for 4 or 12 weeks. Oxidative stress exhibited by dihydroethidium was upregulated at 4 and 12 weeks after onset of diabetes, and nicotinamide treatment reduced oxidative stress at 4 weeks after induction of diabetes. Oxidative DNA damage measured by 8-hydroxy-2′-deoxyguanosine (8-OHdG) increased at 4 and 12 weeks after induction of diabetes and decreased following nicotinamide treatment. The elevated expression of glial fibrillary acidic protein (GFAP) induced by diabetes was attenuated by nicotinamide treatment. In Western blot analysis, the increased expression of cleaved PARP-1 in diabetes was attenuated by nicotinamide treatment at 12 weeks after induction of diabetes. The diabetes-induced apoptosis of inner retinal cells detected by the TUNEL assay was reduced by nicotinamide treatment. In conclusion, nicotinamide attenuated retinal neurodegeneration in diabetes, probably by reducing oxidative DNA damage and supporting DNA repair.