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Histamine 2 receptor antagonism elicits protection against doxorubicin-induced cardiotoxicity in rodent model

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Abstract

Doxorubicin (DOX), an anthracycline-based antibiotic, is regularly used in the management of carcinomas, and haematological malignancies have been downplayed in chemotherapy because of its ability to induce dilated cardiomyopathy (DCM). Dexrazoxane is approved to combat the cardiotoxicity, but limited by its adverse effects. Redox imbalance and reactive oxygen species generation plays major role in DOX-induced cardiotoxicity. Histamine, known to mediate various cardiovascular effects, but nevertheless the role of histamine or its receptors in DOX-induced DCM is remained obscure. Hence, this study is aimed to examine the effect of Famotidine (FAM), a H2 receptor antagonist on DOX-induced DCM in Wistar rats. Myocardial antioxidant status, stress and apoptosis markers, myocardial morphology and function were evaluated as the end points. Treatment with FAM has alleviated DOX doxorubicin-induced cardiotoxicity by reducing oxidative and nitrosative stress evident from lipid peroxidation and total nitrate-to-nitrite ratio, and enhanced the activity of super oxide dismutase. Cardiac stress markers like LDH and Na+-K+ATPase activities as well as CK-MB and Cardiac troponin levels were reduced by FAM treatment. It also normalised the myocardial function as assessed by 2D echocardiography and myocardial index. Treatment imparted anti-apoptotic effect as evident from decrease in myocardial caspase 3 and 9 activity and cleaved PARP expression. Effect of FAM is found to be comparable to the standard ACE inhibitor Captopril (CAP). The results from this study collectively suggest H2 receptor antagonism as a novel therapeutic strategy to impart biochemical, structural and functional improvement indicating its cardio-protective activity.

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Acknowledgements

The authors would like to acknowledge the management of Sri Vishnu College of Pharmacy and Department of Cardiology, Andhra Medical College, Visakhapatnam for their support and encouragement.

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Authors and Affiliations

  1. Department of Pharmacology, Sri Vishnu College of Pharmacy, Bhimavaram, West Godavari, Andhra Pradesh, India

    Sundar Kumar Kondru & Prasad Konduri

  2. Department of Pharmacology, St. Paul’s College of Pharmacy, Turkayamjal, Hyderabad, Telangana, India

    Ajay Godwin Potnuri

  3. Department of Pharmacology and Regulatory Toxicology, National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana, India

    Lingesh Allakonda

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  1. Sundar Kumar Kondru
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  2. Ajay Godwin Potnuri
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Correspondence to Ajay Godwin Potnuri.

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Kondru, S.K., Potnuri, A.G., Allakonda, L. et al. Histamine 2 receptor antagonism elicits protection against doxorubicin-induced cardiotoxicity in rodent model. Mol Cell Biochem 441, 77–88 (2018). https://doi.org/10.1007/s11010-017-3175-x

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