Protective effect of Jasonia montana against ethinylestradiol-induced cholestasis in rats

摘要

Estrogens, and particularly glucuronides such as ethinylestradiol (EE), have been shown to cause cholestasis in animal studies, by reducing bile acid uptake by hepatocytes. The aim of the present article is to investigate anticholestatic activity of the ethanolic extract of the aerial parts of Jasonia montana against liver cholestasis induced by EE in adult female rats in an attempt to understand its mechanism of action, which may pave the way for possible therapeutic applications. Subcutaneous administration of 100@mg/kg b.w. ethinylestradiol to rats induced hepatocellular cholestasis with a significant decrease in serum cholesterol, bile acids and bilirubin levels as well as in hepatic superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) activities and hepatic total, protein-bound and non-protein sulfhydryl groups. Also, treatment with EE produced significant increase in serum Pi-glutathione-s-transferase (Pi-GST), gamma glutamyl transpeptidase (@c-GT) and alpha-glutathione-s-transferase (@a-GST) activities as well as serum nitric oxide (NO) and tumor necrosis factor alpha (TNF-@a) level and hepatic malondialdehyde (MDA) level as compare to control group. Oral administration of the aerial parts of ethanolic extract at a concentration of 150mg/kg b.w. daily to rats treated with EE for 15days showed a significant protection against-induced decrease in serum cholesterol, bile acids and bilirubin levels. The treatment also resulted in a significant increase in hepatic SOD, GPx and GR activities as well as hepatic total, protein-bound and non-protein sulfhydryl groups. In addition, the extract could inhibit serum Pi-GST, @c-GT and @a-GST activities as well as reduce serum TNF-@a, NO and hepatic MDA as compare to ethinylestradiol treated rats. High content of flavonoids and phenolic compounds was found in ethanolic extract, which may be responsible for free radical activity. The results clearly suggest that the aerial parts of J. montana extract may effectively normalize the impaired antioxidant status in ethinylestradiol (EE)-cholestatic model. Thus the extract may have a therapeutic value in drug-induced biliary cholestasis as well as in hormonal therapy.