Cardioprotective effect of ritonavir, an antiviral drug, in isoproterenol induced myocardial necrosis: a new therapeutic implication

Journal of Translational Medicine

Sanjay Kumar Banerjee²  Madhusudana Kuncha²  Tarak Nath Khatua²  Bhavesh Sojitra²  Yogesh Bulani²  Uday Kumar Putcha¹  Abhinav Kanwal²  Prachi Gupta² 

[1] Department of Pathology, National Institute of Nutrition, Hyderabad, India;Division of Medicinal Chemistry and Pharmacology, Indian Institute of Chemical Technology (IICT), Hyderabad, India

关键词: Phlorizin;    Ritonavir;    GLUT;    Oxidative stress;    SGLT1;    Necrosis;    Isoproterenol;   

Others  :  827853
DOI  :  10.1186/1479-5876-11-80

 received in 2012-09-26, accepted in 2013-03-22,  发布年份 2013

【 摘 要 】

Background

Ritonavir is a HIV protease inhibitor. In addition to its antiviral effect, Ritonavir directly inhibits the insulin-regulated glucose transporter GLUT4 and blocks glucose entry into fat and muscle cells. However, the effect of Ritonavir on cardiac GLUT4 inhibition during myocardial necrosis is not investigated. In the present study, we evaluated the role of Ritonavir in isoproterenol-induced myocardial necrosis in vivo and compared the effect with Phlorizin, a nonslective SGLTs inhibitor.

Methods

Isoproterenol (ISO) (150 mg/kg/day, i.p for 2 consecutive days) was administered to mice to cause myocardial necrosis. Phlorizin (400 mg/kg/day i.p twice daily for 2 days) and Ritonavir (10 mg/kg/day i.p twice daily for 2 days) were administered in two different groups of mice before isoproterenol administration.

Results and discussion

Isoproterenol (ISO) (150 mg/kg/day, i.p for 2 consecutive days) administration caused significant (p < 0.05) increase in heart/body weight ratio, and myocardial necrosis as evident by significant (p < 0.05) increase in serum markers i.e. SGOT and CK; and cardiac histopathological changes. Significant (p < 0.05) reduction in myocardial SOD and catalase activities, and GSH level along with a significant (p < 0.05) rise in myocardial TBARS and nitric oxide levels were observed after ISO administration. However, administration of phlorizin, a SGLT1 inhibitor has been found to exhibit partial protection in ISO induced myocardial necrosis, as observed by significant decrease in heart/body weight ratio and myocardial nitric oxide level; significant increase in myocardial SOD and catalase activities along with no histopathological alterations. On the other hand, administration of ritonavir, a nonspecific GLUT inhibitor has been found to exhibit complete protection as observed by normalisation of heart/body weight ratio, serum markers, antioxidant enzymes activities and histopathological alterations. In vitro study with heart homogenate confirmed no antioxidant effect of ritonavir and phlorizin in the absence and presence of isoproterenol.

Conclusions

Our study concluded that ritonavir, a nonspecific GLUT inhibitors showed complete protection in catecholamine induced myocardial necrosis.

【 授权许可】

   
2013 Gupta et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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