Department of Pharmacology, M.V.P Samaj’s College of Pharmacy, Nashik-422002, India.

Department of Pharmacology, M.V.P Samaj’s College of Pharmacy, Nashik-422002, India.

Department of Pharmacology, M.V.P Samaj’s College of Pharmacy, Nashik-422002, India.
Histone deacetylase inhibitor ,Doxorubicin , Sodium valproate ,

Histone deacetylase (HDAC) inhibitors are new class of compounds for the treatment of fibrotic diseases. In the present investigation, the effect of HDAC inhibitor, sodium valproate was studied in an experimental model of myocardial fibrosis. Doxorubicin (adriamycin) can cause cardiac toxicity, cell damage and finally myocardial fibrosis. Myocardial fibrosis was induced by administration of doxorubicin (2.5 mg/kg i.p. thrice a week with cumulative dose of 15 mg/kg for 2 weeks). Sodium valproate (10, 20 and 30 mg/kg, p.o) was administered for 2 weeks. The most widely accepted mechanism of myocardial toxicity is through generation of reactive oxygen species (ROS), which cause mitochondrial cell death results in accumulation of myocardial cell called as fibrosis which leads to collagen deposition. This cell accumulation ultimately leads to increase in the collagen level. The cardiac functional measurements and the left and right ventricular weight indices (LVWI and RVWI respectively) were analyzed. Pathological alteration of level of soluble collagen was examined using hydroxyproline assay. The administration of sodium valproate resulted in a significant improvement in cardiac function, decreases in the cardiac weight indices, reduced fibrous tissue proliferation and levels of soluble collagen with normalization of electrocardioghraphic measurement. Sodium valproate treated groups of animals also showed decrease in level of malondialdehyde with increase in the level of defensive antioxidant enzymes, exerting antioxidant activity along with decrease in collagen deposition. Thus, sodium valproate offers protection against doxorubicin-induced myocardial fibrosis via regulation of collagen synthesis, inhibition of histone deacetylase and antioxidant activity.

5 , 2 , 2015