Cyclosporine A attenuates 3-nitropropionic acid-induced Huntington-like symptoms in rats: possible nitric oxide mechanism.
Cyclosporine A is a well-known immunosuppressant drug that is currently used for prevention of allograft rejection. The current study was conducted to explore the therapeutic potential of cyclosporine A against 3-nitropropionic acid (3-NP)-induced neurotoxicity, an animal model of Huntington disease (HD). Systemic administration of 3-NP (10 mg/kg) for 14 days significantly impaired body weight, motor activity, biochemical parameters (raised lipid peroxidation, nitrite concentration, depletion of superoxide dismutase [SOD] and catalase), and mitochondrial enzymes. Cyclosporine A (2.5, 5, and 10 mg/kg) treatment significantly attenuated behavioral, biochemical, and cellular alterations. Furthermore, L-arginine pretreatment with cyclosporine A (5 mg/kg) significantly reversed the protective effect of cyclosporine A. However, L-nitro-arginine methyl ester (L-NAME; 10 mg/kg) pretreatment potentiated the protective effect of cyclosporine A (5 mg/kg). Study highlights the therapeutic potential of cyclosporine A in the treatment of HP. Study suggests that nitric oxide (NO) modulation is involved in the neuroprotective effect of cyclosporine A against 3-NP neurotoxicity.
Kumar
Puneet
P
University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India. kumaruips@yahoo.com
Kalonia
Harikesh
H
Kumar
Anil
A
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D016572:Cyclosporine / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D006816:Huntington Disease / Q000139:chemically induced / Q000188:drug therapy*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009498:Neurotoxins / Q000633:toxicity*; D009569:Nitric Oxide / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D009573:Nitrites / Q000378:metabolism; D009574:Nitro Compounds / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D011422:Propionates / Q000633:toxicity*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
D018696:Neuroprotective Agents; D009498:Neurotoxins; D009573:Nitrites; D009574:Nitro Compounds; D011422:Propionates; D009569:Nitric Oxide; D016572:Cyclosporine; D002374:Catalase; D013482:Superoxide Dismutase; C015392:3-nitropropionic acid