Effect of carvedilol on behavioral, mitochondrial dysfunction, and oxidative damage against D-galactose induced senescence in mice.
Growing evidence indicates that oxidative stress and mitochondrial dysfunction plays a critical role in brain aging. Chronic injection of D-galactose can cause gradual deterioration in learning and memory capacity and serve as an animal model of aging. Recently, potential therapeutic effect of carvedilol (CAR) has been reported by virtue of which its antioxidant and mitochondrial permeability transitional property. The present study has been designed to explore the CAR effect against D-galactose-induced behavioral, biochemical, and mitochondrial dysfunction in mice. Systemic administration of D-galactose for 6 weeks significantly impaired behavioral (learning and memory and locomotor activity), biochemical parameters (raised lipid peroxidation, nitrite concentration, depletion of reduced glutathione, and catalase activity), and mitochondrial enzymes (decreased complex I, II and III enzymes levels) as compared to sham group. CAR (2.5 and 5 mg/kg) treatment significantly improved behavioral abnormalities and biochemical and cellular alterations as compared to control. Chronic administration of D-galactose for a period of 6 week results into a significant increase of acetylcholine esterase enzyme level. CAR (2.5 and 5 mg/kg) treatment significantly attenuated the elevated level of acetylcholine esterase of mice. In conclusion, present studies highlight the protective effects of CAR against D-galactose-induced behavioral, biochemical, and mitochondrial dysfunction in mice. The study further provides a hope that CAR could be used in the management of cognitive dysfunction and related symptoms during aging.
Kumar
Anil
A
Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre for Advance Studies, Panjab University, Chandigarh, 160014, India. kumaruips@yahoo.com
Dogra
Samrita
S
Prakash
Atish
A
D000110:Acetylcholinesterase / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000375:Aging / Q000187:drug effects*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002227:Carbazoles / Q000008:administration & dosage / Q000494:pharmacology*; D000077261:Carvedilol; D003072:Cognition Disorders / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005690:Galactose; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D011412:Propanolamines / Q000008:administration & dosage / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D000110:Acetylcholinesterase; D005690:Galactose
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