Amelioration of neurological and biochemical deficits by peroxynitrite decomposition catalysts in experimental diabetic neuropathy

Abstract

Diabetic neuropathy, a major complication of diabetes, affects more than 60% of diabetic patients. Recently, involvement of peroxynitrite has been postulated in diabetic neuropathy. In the present study, we have studied the effects of peroxynitrite decomposition catalysts (PDC's)-5,10,15,20-tetrakis(4-sulfonatophenyl) porphyrinato iron(III) [FeTPPS] and 5,10,15,20-tetrakis(N-methyl-4-pyridyl)porphyrinato iron(III) [FeTMPyP]-in experimental diabetic neuropathy. Male Sprague-Dawley rats, with six weeks of untreated diabetes were treated for two weeks with peroxynitrite decomposition catalysts. Diabetic animals showed a significant decrease in motor nerve conduction velocity and nerve blood flow, nociception as evident from decreased tail flick latency (hyperalgesia) and increased paw withdrawal pressure (mechanical allodynia) along with elevation in peroxynitrite and reduction in nerve glutathione levels. Two weeks treatment with PDC's significantly improved all the above stated functional and biochemical deficits. Aftermath of this study advocates the beneficial effects of peroxynitrite decomposition catalysts in experimental diabetic neuropathy.