Protective effects of 4-amino1,8-napthalimide, a poly (ADP-ribose) polymerase inhibitor in experimental diabetic neuropathy.
Peripheral diabetic neuropathy is a heterogeneous group of disorders, and is known to affect 50-60% of diabetic patients. Poly (ADP-ribose) polymerase (PARP) activation has been identified as one of the key components in the pathogenesis of diabetic neuropathy. In the present study we have targeted PARP overactivation in diabetic neuropathy using a known PARP inhibitor, 4 amino 1, 8-napthalimide (4-ANI). Streptozotocin induced diabetic rats developed neuropathy within 6 weeks, which was evident from significant reduction in motor nerve conduction velocity (MNCV), nerve blood flow (NBF) along with neuropathic pain and abnormal sensory perception. Six weeks after diabetes induction Sprague Dawley rats were treated with 4-ANI (3 and 10 mg/kg, p.o.) for a period of two weeks (seventh and eighth weeks). Two week treatment with 4-ANI showed improvement in nerve conduction, nerve blood flow and reduction in tail flick responses and mechanical allodynia in diabetic animals. 4-ANI also attenuated PAR immunoreactivity and NAD depletion in nerves of diabetic animals. Results of present study suggest the potential of PARP inhibitors like 4-ANI in the treatment of diabetic neuropathy.
Sharma
Shyam S
SS
Molecular Neuropharmacology Laboratory, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar (Mohali), Punjab-160062, India. sssharma@niper.ac.in
Kumar
Ashutosh
A
Kaundal
Ravinder K
RK
D015057:1-Naphthylamine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000201:enzymology; D003929:Diabetic Neuropathies / Q000201:enzymology*; D006801:Humans; D008297:Male; D009243:NAD / Q000378:metabolism; D053644:Naphthalimides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use*; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology; D010147:Pain Measurement; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D015363:Quinolones / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin
D053644:Naphthalimides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D015363:Quinolones; D009243:NAD; C086538:4-amino-1,8-naphthalimide; D013311:Streptozocin; D015057:1-Naphthylamine; D011065:Poly(ADP-ribose) Polymerases