title: Protective role of atorvastatin against doxorubicin-induced cardiotoxicity and testicular toxicity in mice.
abstract: Doxorubicin (DOX), a potent chemotherapeutic agent, is widely used for the treatment of various malignancies. However, its clinical uses are limited due to its dose-dependent adverse effects particularly cardiac and testicular toxicities. DOX-induced toxicity is mainly due to the induction of oxidative stress. Atorvastatin (ATV), a 3-hydroxy 3-methyl glutaryl coenzyme A reductase inhibitor, with lipid-lowering activity, acts as an antioxidant at lower doses. It possesses pleiotropic effects independent of cholesterol-lowering property usually shown at lower doses, which include antioxidant and anti-inflammatory activities. The present study was aimed to investigate the possible protection exerted by atorvastatin against oxidative stress and DNA damage induced by DOX in the heart and testes of mice. The protective role of ATV in the heart and testes of DOX-treated mice was evident from the amelioration of oxidative stress, DNA and cellular damage. The present study clearly indicates that ATV offers a significant protection against DOX-induced oxidative stress and DNA damage in the heart and testes of mice.
authors: Department of Toxicology, NCER&D, Piramal Healthcare Limited, Goregaon East, Mumbai, Maharashtra, India. ramanji.niper@gmail.com
authors: S V V S
authors: SV
authors: Ramanjaneyulu
authors: P P
authors: PP
authors: Trivedi
authors: S
authors: S
authors: Kushwaha
authors: A
authors: A
authors: Vikram
authors: G B
authors: GB
authors: Jena
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D000069059:Atorvastatin; D009202:Cardiomyopathies / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D020552:Comet Assay; D053938:DNA Fragmentation / Q000187:drug effects; D004317:Doxorubicin; D005978:Glutathione / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D006538:Heptanoic Acids / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D015162:Micronucleus Tests; D018384:Oxidative Stress / Q000187:drug effects; D011758:Pyrroles / Q000494:pharmacology*; D013733:Testicular Diseases / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D013737:Testis / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D006538:Heptanoic Acids; D011758:Pyrroles; D008315:Malondialdehyde; D004317:Doxorubicin; D000069059:Atorvastatin; D005978:Glutathione
references: Eur J Pharmacol. 2007 Aug 27;569(3):204-11
references: 17669395
references: Eur J Clin Pharmacol. 2004 Dec;60(10):685-91
references: 15490140
references: Anal Biochem. 1979 Jun;95(2):351-8
references: 36810
references: Atherosclerosis. 1998 Jun;138(2):271-80
references: 9690910
references: Pharmacol Res. 1989 Nov-Dec;21(6):729-34
references: 2626399
references: Reprod Toxicol. 2006 Jan;21(1):54-9
references: 16112542
references: Clin Nucl Med. 2009 Nov;34(11):762-7
references: 19851170
references: Proc Natl Acad Sci U S A. 1975 Nov;72(11):4425-9
references: 1060122
references: Biochim Biophys Acta. 1979 Jan 4;582(1):67-78
references: 760819
references: J Ethnopharmacol. 2008 Apr 17;117(1):123-9
references: 18346858
references: Semin Oncol. 1992 Dec;19(6):670-86
references: 1462166
references: Bioorg Med Chem Lett. 2008 Feb 1;18(3):1102-5
references: 18164200
references: J Biol Chem. 2006 Apr 7;281(14):9337-45
references: 16464853
references: Br J Pharmacol. 2006 Dec;149(8):988-97
references: 17088865
references: Food Chem Toxicol. 2010 May;48(5):1178-84
references: 20146931
references: Circulation. 2004 Jun 15;109(23 Suppl 1):III39-43
references: 15198965
references: Toxicol Appl Pharmacol. 2008 Jan 1;226(1):84-93
references: 17950394
references: Basic Res Cardiol. 2002 Mar;97(2):105-16
references: 12002257
references: Drug Saf. 2000 Apr;22(4):263-302
references: 10789823
references: Int J Cardiol. 2011 Jul 15;150(2):193-200
references: 20452068
references: Cardiovasc Toxicol. 2011 Sep;11(3):215-25
references: 21553131
references: Food Chem Toxicol. 2010 Jun;48(6):1425-38
references: 20385199
references: Fertil Steril. 2006 Apr;85 Suppl 1:1216-22
references: 16616095
references: Chem Biol Interact. 2006 Mar 25;160(2):108-14
references: 16434030
references: Biol Reprod. 1999 Sep;61(3):809-12
references: 10456861
references: J Agric Food Chem. 2010 Aug 25;58(16):8977-82
references: 20666448
references: Int J Pharm. 2007 Jun 7;337(1-2):346-56
references: 17306479
references: Pediatr Nephrol. 2008 Dec;23(12):2185-94
references: 18791746
references: Mutat Res. 2010 Dec 21;703(2):115-21
references: 20713175
references: Fundam Appl Toxicol. 1994 Oct;23(3):439-46
references: 7835544
references: Food Chem Toxicol. 2010 Mar;48(3):951-6
references: 20060872
references: J Clin Hypertens (Greenwich). 2012 Apr;14(4):245-9
references: 22458746
references: Circ Res. 2008 Nov 21;103(11):1270-9
references: 18948619
references: Cancer Lett. 1999 Feb 8;136(1):41-6
references: 10211937
references: Clin Breast Cancer. 2003 Apr;4 Suppl 1:S26-33
references: 12756076
references: Cancer Res. 2009 Jan 15;69(2):695-9
references: 19147586
references: Arterioscler Thromb Vasc Biol. 2002 Feb 1;22(2):300-5
references: 11834532
references: Pharmacol Res. 1992 Sep;26(2):143-50
references: 1409255
references: Am Heart J. 2000 Aug;140(2):249-52
references: 10925339
references: Circ J. 2010 May;74(5):818-26
references: 20424337
references: Chem Biol Interact. 2010 Jan 5;183(1):85-97
references: 19900424
references: Cancer Chemother Pharmacol. 2004 Feb;53(2):141-50
references: 14564477
references: Exp Cell Res. 1988 Mar;175(1):184-91
references: 3345800
references: Int J Cardiol. 2006 Apr 28;109(1):7-15
references: 16054715
references: Mol Cell Biochem. 2004 Dec;267(1-2):209-14
references: 15663203
references: Food Chem Toxicol. 2011 Apr;49(4):838-47
references: 21168534
references: Mutat Res. 1997 Jun 13;391(1-2):87-9
references: 9219552
references: Br J Pharmacol. 2009 Jan;156(1):48-61
references: 19133991
references: Biochem Biophys Res Commun. 2009 May 1;382(2):462-7
references: 19292979
references: Hum Exp Toxicol. 2011 Feb;30(2):102-9
references: 20418268
references: Pharmacol Res. 2009 Apr;59(4):242-7
references: 19429465
references: J Biol Chem. 1951 Nov;193(1):265-75
references: 14907713