Salubrious effect of <i>Parinari curatellifolia</i> seed extract in doxorubicin intoxicated rats

Abstract

The seed of Parinari curatellifolia Ex Benth (Chrysobalanaceae) is widely used in Southwestern Nigeria for the treatment of diabetes and hypertension, important cardiovascular disease (CVD) risk factors. This study was designed to investigate the effect of Parinari curatellifolia seed extract (PCE) on the antioxidant status, lipid profile and cardiac health in doxorubicin (DOX) induced cardiotoxicity. Phenolic profile of the extract was determined by high performance liquid chromatography-diode array detector (HPLC-DAD). Male Wistar rats were divided into seven groups that were pretreated with ramipril (10 mg/kg) or PCE (50-, 100-, 150- and 200 mg/kg) orally for two weeks. On the 13^th day, single dose of (15 mg/kg i.p) DOX was administered to all the groups except control. Antioxidant parameters (superoxide dismutase {SOD}, glutathione peroxidase {GPx}, glutathione transferase {GT}, reduced glutathione {GSH}, thiobarbituric reacting substance {TBARS}), cholesterol, triglycerides, low density lipoprotein (LDL) and high density lipoprotein (HDL); lactate dehydrogenase (LDH) and creatine kinase (CK-MB) were evaluated in cardiac tissue homogenate or plasma. Catechin, epicatechin, quercetin, isoquercitrin, rutin, kaempferol and quercitrin were confirmed present in PCE. DOX intoxication in experimental rats resulted in significant increase (P<0.05) in plasma activities of LDH and CK-MB, concentrations of all lipid types, except HDL which was significantly (P<0.05) reduced, as well as the tissue level of TBARS as compared with control. In addition, activities of the antioxidant enzymes (SOD, GT and GPx) were reduced (P<0.05) in the DOX intoxicated group. However, pretreatment with PCE significantly ameliorated the alterations caused by doxorubicin. PCE protected against doxorubicin-induced cardiotoxicity in rats possibly through positive modulation of the cardiac antioxidant defense system and amelioration of dyslipidemia by the constituent flavonols.

Keywords: Parinari curatellifolia, cardiotoxicity, Doxorubicin, antioxidant, phenolic compounds, dyslipidemia