title: Effect of carvedilol on behavioral, mitochondrial dysfunction, and oxidative damage against D-galactose induced senescence in mice.
abstract: 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.
authors.affiliation: Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre for Advance Studies, Panjab University, Chandigarh, 160014, India. kumaruips@yahoo.com
authors.forename: Anil
authors.initials: A
authors.lastname: Kumar
authors.forename: Samrita
authors.initials: S
authors.lastname: Dogra
authors.forename: Atish
authors.initials: A
authors.lastname: Prakash
mesh_terms: 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*
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D000110:Acetylcholinesterase; D005690:Galactose
references.citation: Arch Biochem Biophys. 1959 May;82(1):70-7
references.pmid: 13650640
references.citation: Behav Brain Res. 2005 Feb 28;157(2):245-51
references.pmid: 15639175
references.citation: Biochem J. 1999 Oct 15;343 Pt 2:419-23
references.pmid: 10510309
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 1992 Jan;16(1):117-25
references.pmid: 1557503
references.citation: J Pharmacol Exp Ther. 1996 Apr;277(1):128-36
references.pmid: 8613909
references.citation: Br J Pharmacol. 2002 May;136(2):193-200
references.pmid: 12010767
references.citation: J Neurochem. 1997 Aug;69(2):581-93
references.pmid: 9231715
references.citation: Behav Brain Res. 2006 Aug 10;171(2):251-60
references.pmid: 16707173
references.citation: Biochem J. 1966 Jun;99(3):667-76
references.pmid: 5964963
references.citation: Neurol Res. 2003 Oct;25(7):749-53
references.pmid: 14579794
references.citation: Acta Physiol Scand. 2004 Dec;182(4):321-31
references.pmid: 15569093
references.citation: Circulation. 2002 Feb 26;105(8):975-80
references.pmid: 11864928
references.citation: J Bioenerg Biomembr. 2004 Aug;36(4):309-12
references.pmid: 15377863
references.citation: Methods Enzymol. 1981;77:398-405
references.pmid: 7329316
references.citation: Nephron. 2002;92(3):685-92
references.pmid: 12372956
references.citation: Exp Gerontol. 2006 Jul;41(7):668-73
references.pmid: 16677790
references.citation: Ageing Res Rev. 2006 Feb;5(1):1-13
references.pmid: 16084778
references.citation: Biochem Pharmacol. 1961 Jul;7:88-95
references.pmid: 13726518
references.citation: Stroke. 1992 Nov;23(11):1630-5; discussion 1635-6
references.pmid: 1440712
references.citation: Brain Res. 1998 Jul 20;799(2):215-29
references.pmid: 9675286
references.citation: Arch Biochem Biophys. 1978 Feb;186(1):189-95
references.pmid: 24422
references.citation: Life Sci. 2007 Apr 24;80(20):1897-905
references.pmid: 17391708
references.citation: Psychoneuroendocrinology. 2006 Aug;31(7):805-11
references.pmid: 16707226
references.citation: J Mol Cell Cardiol. 2009 Jun;46(6):989-97
references.pmid: 19318235
references.citation: J Cereb Blood Flow Metab. 2000 Aug;20(8):1197-204
references.pmid: 10950380
references.citation: Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2005 Dec;149(2):389-92
references.pmid: 16601795
references.citation: Nutr Neurosci. 2005 Apr;8(2):67-89
references.pmid: 16053240
references.citation: J Ethnopharmacol. 2007 May 22;111(3):504-11
references.pmid: 17224253
references.citation: Biochem Pharmacol. 2001 Jul 15;62(2):241-8
references.pmid: 11389884
references.citation: Aging Cell. 2003 Feb;2(1):1-7
references.pmid: 12882328
references.citation: Ann N Y Acad Sci. 1994 Nov 17;738:230-42
references.pmid: 7832432
references.citation: J Neurochem. 1999 Sep;73(3):1127-37
references.pmid: 10461904
references.citation: J Pharmacol Exp Ther. 2000 Dec;295(3):1022-30
references.pmid: 11082437
references.citation: Mech Ageing Dev. 1999 May 17;108(3):239-51
references.pmid: 10405984
references.citation: J Biol Chem. 1949 Feb;177(2):751-66
references.pmid: 18110453
references.citation: J Neurol Sci. 2009 Feb 15;277(1-2):58-64
references.pmid: 19007942
references.citation: Br J Pharmacol. 2000 Apr;129(7):1530-5
references.pmid: 10742311
references.citation: Biochem Biophys Res Commun. 2008 May 16;369(4):1082-7
references.pmid: 18329384
references.citation: Life Sci. 1999;65(18-19):1943-50
references.pmid: 10576443