Cardioprotective effect of ritonavir, an antiviral drug, in isoproterenol induced myocardial necrosis

A new therapeutic implication

Prachi Gupta, Abhinav Kanwal, Uday Kumar Putcha, Yogesh Bulani, Bhavesh Sojitra, Tarak Nath Khatua, Madhusudana Kuncha, Sanjay Kumar Banerjee

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number80
JournalJournal of Translational Medicine
Volume11
Issue number1
DOIs
Publication statusPublished - 26-03-2013

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Ritonavir
Isoproterenol
Antiviral Agents
Necrosis
Phlorhizin
Body Weight
Therapeutics
Catalase
Nitric Oxide
Antioxidants
Biomarkers
HIV Protease Inhibitors
Facilitative Glucose Transport Proteins
Enzyme activity
Aspartate Aminotransferases
Adipocytes
Muscle Cells
Catecholamines
Muscle
Fats

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Gupta, Prachi ; Kanwal, Abhinav ; Putcha, Uday Kumar ; Bulani, Yogesh ; Sojitra, Bhavesh ; Khatua, Tarak Nath ; Kuncha, Madhusudana ; Banerjee, Sanjay Kumar. / Cardioprotective effect of ritonavir, an antiviral drug, in isoproterenol induced myocardial necrosis : A new therapeutic implication. In: Journal of Translational Medicine. 2013 ; Vol. 11, No. 1.
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abstract = "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.",
author = "Prachi Gupta and Abhinav Kanwal and Putcha, {Uday Kumar} and Yogesh Bulani and Bhavesh Sojitra and Khatua, {Tarak Nath} and Madhusudana Kuncha and Banerjee, {Sanjay Kumar}",
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Cardioprotective effect of ritonavir, an antiviral drug, in isoproterenol induced myocardial necrosis : A new therapeutic implication. / Gupta, Prachi; Kanwal, Abhinav; Putcha, Uday Kumar; Bulani, Yogesh; Sojitra, Bhavesh; Khatua, Tarak Nath; Kuncha, Madhusudana; Banerjee, Sanjay Kumar.

In: Journal of Translational Medicine, Vol. 11, No. 1, 80, 26.03.2013.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Cardioprotective effect of ritonavir, an antiviral drug, in isoproterenol induced myocardial necrosis

T2 - A new therapeutic implication

AU - Gupta, Prachi

AU - Kanwal, Abhinav

AU - Putcha, Uday Kumar

AU - Bulani, Yogesh

AU - Sojitra, Bhavesh

AU - Khatua, Tarak Nath

AU - Kuncha, Madhusudana

AU - Banerjee, Sanjay Kumar

PY - 2013/3/26

Y1 - 2013/3/26

N2 - 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.

AB - 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.

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