α-Bisabolol abrogates isoproterenol-induced myocardial infarction by inhibiting mitochondrial dysfunction and intrinsic pathway of apoptosis in rats

Mohamed Fizur Nagoor Meeran, Farah Laham, Sheikh Azimullah, Saeed Tariq, Shreesh Ojha

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

Mitochondrial dysfunction plays crucial role in the pathologenesis of myocardial infarction (MI). The present study evaluated the protective effect of α-bisabolol against isoproterenol (ISO)-induced mitochondrial dysfunction and apoptosis in rats. Male albino Wistar rats were pre- and co-treated with intraperitoneal injection of α-bisabolol (25 mg/kg body weight) daily for 10 days. To induce experimental MI, ISO (85 mg/kg body weight) was injected subcutaneously to the rats at an interval of 24 h for 2 days (9th and 10th day). ISO-induced MI was indicated by the decreased activities of heart creatine kinase and lactate dehydrogenase in rats. ISO administration also enhanced the concentrations of heart mitochondrial lipid peroxidation products and decreased the activities/concentrations of mitochondrial antioxidants, Kreb’s cycle dehydrogenases and mitochondrial electron transport chain complexes I, II + III and IV in rats. Furthermore, ISO triggers calcium overload and ATP depletion in the rat’s heart mitochondria followed by the mitochondrial cytochrome-C release and the activation of intrinsic pathway of apoptosis by upregulating the myocardial pro-apoptotic Bax, P 53 , APAF-1, active caspase-3, active caspase-9 and down regulating the expressions of anti-apoptotic Bcl-2. α-Bisabolol pre and co-treatment showed considerable protective effects on all the biochemical and molecular parameters studied. Transmission electron microscopic study and mitochondrial swelling assay confirmed our biochemical and molecular findings. The in vitro study on hydroxyl radical also revealed the potent free radical scavenging activity of α-bisabolol. Thus, α-bisabolol attenuates mitochondrial dysfunction and intrinsic pathway of apoptosis in ISO-induced myocardial infarcted rats.

Original languageEnglish
Pages (from-to)89-102
Number of pages14
JournalMolecular and cellular biochemistry
Volume453
Issue number1-2
DOIs
Publication statusPublished - Mar 15 2019

Keywords

  • Calcium overload
  • Intrinsic apoptotic pathway
  • Isoproterenol
  • Mitochondrial dysfunction
  • Oxidative stress
  • α-Bisabolol

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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