Targeting oxidative stress attenuates malonic acid induced Huntington like behavioral and mitochondrial alterations in rats.
Objective of the present study was to explore the possible role of oxidative stress in the malonic acid induced behavioral, biochemical and mitochondrial alterations in rats. In the present study, unilateral single injections of malonic acid at different doses (1.5, 3 and 6 micromol) were made into the ipsilateral striatum in rats. Behavioral parameters were accessed on 1st, 7th and 14th day post malonic acid administration. Oxidative stress parameters and mitochondrial enzyme functions were assessed on day 14 after behavioral observations. Ipsilateral striatal malonic acid (3 and 6 micromol) administration significantly reduced body weight, locomotor activity, motor coordination and caused oxidative damage (lipid peroxidation, nitrite, superoxide dismutase, catalase and glutathione) in the striatum as compared to sham treated animal. Mitochondrial enzyme complexes and MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolinium bromide) activity were significantly inhibited by malonic acid. Vitamin E treatment (50 and 100 mg/kg, p.o.) significantly reversed the various behavioral, biochemical and mitochondrial alterations in malonic acid treated animals. Our findings show that targeting oxidative stress by vitamin E in malonic acid model, results in amelioration of behavioral and mitochondrial alterations are linked to inhibition of oxidative damage. Based upon these finding present study hypothesize that protection exerted by vitamin E on behavioral, mitochondrial markers indicates the possible preservation of the functional status of the striatal neurons by targeting the deleterious actions of oxidative stress.
Kalonia
Harikesh
H
Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study (UGC-CAS), Panjab University, Chandigarh, India.
Kumar
Puneet
P
Kumar
Anil
A
D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods*; D006816:Huntington Disease / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008297:Male; D008314:Malonates / Q000037:antagonists & inhibitors / Q000633:toxicity*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014810:Vitamin E / Q000008:administration & dosage
D008314:Malonates; D014810:Vitamin E; C030290:malonic acid