Department of Biochemistry, Faculty of Pharmacy, October 6th University, Cairo, Egypt.
Saudi Pharm J. 2010 Jan;18(1):27-33. doi: 10.1016/j.jsps.2009.12.002. Epub 2009 Dec 23.
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 μg/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 (γ-GT) and alpha-glutathione-s-transferase (α-GST) activities as well as serum nitric oxide (NO) and tumor necrosis factor alpha (TNF-α) level and hepatic malondialdehyde (MDA) level as compare to control group. Oral administration of the aerial parts of ethanolic extract at a concentration of 150 mg/kg b.w. daily to rats treated with EE for 15 days 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, γ-GT and α-GST activities as well as reduce serum TNF-α, 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.
雌激素，特别是结合雌激素如乙炔雌二醇（EE），在动物研究中已被证明可通过减少肝细胞摄取胆汁酸而导致胆汁淤积。本文的目的是研究蒙大拿州 Jasminia 地上部分的乙醇提取物对 EE 诱导的成年雌性大鼠肝内胆汁淤积的抗胆汁淤积活性，试图了解其作用机制，这可能为可能的治疗应用铺平道路。皮下给予 100μg/kg bw 乙炔雌二醇可诱导肝细胞性胆汁淤积，导致血清胆固醇、胆汁酸和胆红素水平以及肝超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GPx）、谷胱甘肽还原酶（GR）活性和肝总、蛋白结合和非蛋白巯基水平显著降低。此外，EE 处理导致血清 Pi-谷胱甘肽-S-转移酶（Pi-GST）、γ-谷氨酰转肽酶（γ-GT）和 α-谷胱甘肽-S-转移酶（α-GST）活性以及血清一氧化氮（NO）和肿瘤坏死因子-α（TNF-α）水平和肝丙二醛（MDA）水平显著升高与对照组相比。每天口服浓度为 150mg/kg bw 的地上部分乙醇提取物，连续 15 天治疗 EE 诱导的大鼠，可显著防止 EE 诱导的血清胆固醇、胆汁酸和胆红素水平降低。该治疗还导致肝 SOD、GPx 和 GR 活性以及肝总、蛋白结合和非蛋白巯基水平显著增加。此外，与 EE 处理的大鼠相比，该提取物可抑制血清 Pi-GST、γ-GT 和 α-GST 活性，并降低血清 TNF-α、NO 和肝 MDA。在乙醇提取物中发现了大量的类黄酮和酚类化合物，这可能是自由基活性的原因。结果清楚地表明，J. montana 地上部分提取物可能有效地使 EE 诱导的胆汁淤积模型中受损的抗氧化状态正常化。因此，该提取物在药物诱导的胆汁淤积和激素治疗中可能具有治疗价值。
