Protective role of atorvastatin against doxorubicin-induced cardiotoxicity and testicular toxicity in mice

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 oxidat...

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Bibliographic Details
Published in:Journal of physiology and biochemistry 2013-09, Vol.69 (3), p.513-525
Main Authors: SVVS, Ramanjaneyulu, Trivedi, P. P., Kushwaha, S., Vikram, A., Jena, G. B.
Format: Article
Language:English
Subjects:
Animal Physiology
Animals
Antioxidants - pharmacology
Atorvastatin Calcium
Biomedical and Life Sciences
Biomedicine
Cardiomyopathies - chemically induced
Cardiomyopathies - metabolism
Cardiomyopathies - prevention & control
Comet Assay
DNA Fragmentation - drug effects
Doxorubicin
Glutathione - metabolism
Heart - drug effects
Heptanoic Acids - pharmacology
Human Physiology
Lipid Peroxidation - drug effects
Male
Malondialdehyde - metabolism
Mice
Micronucleus Tests
Original Paper
Oxidative Stress - drug effects
Pyrroles - pharmacology
Testicular Diseases - chemically induced
Testicular Diseases - metabolism
Testicular Diseases - prevention & control
Testis - drug effects
Testis - metabolism
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Summary: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.
ISSN:1138-7548
1877-8755
DOI:10.1007/s13105-013-0240-0