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Protective effects of Terminalia arjuna against Doxorubicin-induced cardiotoxicity
Authors:Singh Gurvinder  Singh Anu T  Abraham Aji  Bhat Beena  Mukherjee Ashok  Verma Ritu  Agarwal Shiv K  Jha Shivesh  Mukherjee Rama  Burman Anand C
Institution:Dabur Research Foundation, 22 Site IV, Sahibabad, Ghaziabad 201010, U.P., India.
Abstract:Terminalia arjuna has been marked as a potential cardioprotective agent since vedic period. The present study was aimed to investigate the effects of butanolic fraction of Terminalia arjuna bark (TA-05) on Doxorubicin (Dox)-induced cardiotoxicity. Male wistar rats were used as in vivo model for the study. TA-05 was administered orally to Wistar rats at different doses (0.42 mg/kg, 0.85 mg/kg, 1.7 mg/kg, 3.4 mg/kg and 6.8 mg/kg) for 6 days/week for 4 weeks. Thereafter, all the animals except saline and TA-05-treated controls were administered 20 mg/kg Dox intraperitonially. There was a significant decrease in myocardial superoxide dismutase (38.94%) and reduced glutathione (23.84%) in animals treated with Dox. Concurrently marked increase in serum creatine kinase-MB (CKMB) activity (48.11%) as well as increase in extent of lipid peroxidation (2.55-fold) was reported. Co-treatment of TA-05 and Dox resulted in an increase in the cardiac antioxidant enzymes, decrease in serum CKMB levels and reduction in lipid peroxidation as compared to Dox-treated animals. Electron microscopic studies in Dox-treated animals revealed mitochondrial swelling, Z-band disarray, focal dilatation of smooth endoplasmic reticulum (SER) and lipid inclusions, whereas the concurrent administration of TA-05 led to a lesser degree of Dox-induced histological alterations. These findings suggest that butanolic fraction of Terminalia arjuna bark has protective effects against Dox-induced cardiotoxicity and may have potential as a cardioprotective agent.
Keywords:CKMB  creatine kinase  Dox  doxorubicin  DTNB  [5  5-dithiobis(2-nitrobenzoic acid)]  DPPH  [1  1-diphenyl-2-picrylhydrazyl]  GSH  reduced glutathione  MDA  malonyldialdehyde  mg  milligram  NADH  nicotinamide adenine dinucleotide-reduced disodium salt  ROS  reactive oxygen species  SER  smooth endoplasmic reticulum  SDS  sodium dodecyl sulphate  SOD  superoxide dismutase  TBA  thiobarbituric acid  TBARS  thiobarbituric acid reactive substances  TCA  trichloroacetic acid  IR  ischemic reperfusion
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