Functional Oil from Black Seed Differentially Inhibits Aldose-reductase and Ectonucleotidase Activities by Up-regulating Cellular Energy in Haloperidol-induced Hepatic Toxicity in Rat Liver.

Abstract

In this study, the effect of rate-limiting enzymes involved in degradation of hepatic adenosine and intracellular sorbitol was investigated in rats exposed to haloperidol (HAL) and treated with functional oil (FO), containing principal active phytochemicals from black seed. Animals were divided into six groups (n=10): Distilled water, HAL 15 mg/kg, pre-administration/HAL 15 mg/kg, co-administration/HAL 15 mg/kg, post-administration/HAL 15 mg/kg, FO 150 mg/kg. The results of this study revealed that the activities of ectonucleotidase and aldose-reductase were significantly increased in HAL-treated rats when compared with the control (p < 0.05). However, differential treatments (pre, co and post) with FO depleted the activities of these enzymes compared with HAL-treated rats. Furthermore, therapeutic HAL administration increased the levels of key hepatic biomarkers (ALT, AST, and ALP) and malondialdehyde level with a concomitant decrease in functional hepatic cellular ATP. However, differential treatment with FO increases hepatic ATP and non-enzymatic antioxidant status, with a concomitant decrease in the levels of malondialdehyde and liver biomarkers. Therefore, results of this finding underlined the importance of aldose-reductase and econucleotidase activities in HAL induced toxicity and suggest some possible mechanisms of action by which FO prevent HAL-induced hepatic toxicity in rats.