Effect of 17?-ethinylestradiol on activity of rat liver enzymes for synthesis and hydrolysis of cholesterol esters

Nikitin, Yu. P.; Душкин, М. И.; Dolgov, A. V.; Gordienko, Irina

doi:10.1007/bf00836193

“…Prolonged blockade of bile duct can cause decreased elimination of conjugated bilirubin and an increase in conjugated level in plasma, a symptom diagnostic for obstructive jaundice (Cotran et al, 1999). Ethinylestradiol was reported to decrease serum cholesterol level which is accompanied with an increase in hepatic cholesterol level (Nikitin et al, 1986). EE stimulates low density lipoprotein receptor activity and increases the binding of lipoproteins to liver plasma membrane (Bertolotti and Spady, 1996).…”

Section: Discussionmentioning

confidence: 98%

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

Hussein

¹

,

Abdel‐Gawad

²

2010

Saudi Pharmaceutical Journal

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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.

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“…Therefore damage to the liver inflicted by a hepatotoxic agent is of critical consequence [5]. The changes is associated with EE-induced liver toxicity are comparable to that of hepatic cholestasis [39,40]. This is due to the infiltration of fatty acids and glycerols into the hepatocytes upon damage to cell membranes [41][42][43].…”

Section: Discussionmentioning

confidence: 99%

Resveratrol Nanoemulsion: A Promising Protector Against Ethinylestradiol-Induced Hepatic Cholestasis in Female Rats

Ma¹,

Ak²,

At³

et al. 2019

J Biomol Res Ther

0

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Ethinylestradiol (EE) induced cholestasis was reported in female rats-model. The present article aimed to investigate anticholestatic activity of Resveratrol Nanoemulsion (RENE) against EE-induced cholestasis in adult female rats. The mean particle size of RENE was 49.5 ± 0.05 nm and zeta potential of +15.75 with the observed shapes of nanoparticle was spherical. Also, the median lethal dose (LD50) of RENE in rats was 795 mg/kg body weight. Administration of 1/20 LD50 RENE (39.75 mg/kg.b.w.) to EE-treated rats normalize serum cholesterol level as well as against an increase of serum TBA, bilirubin concentration. The treatment also resulted in a significant increase in hepatic SOD and GPx. RENE inhibited serum ALP, ALT and γ-GT activities, as well as reduced serum TNF-α, NO, MMP-2 MMP-9 and hepatic MDA as compared to EE-treated rats. The results clearly suggest that RENE has a powerful prophylactic action in cholestasis induced by EE.

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Prophylactic Effect of Resveratrol Against Ethinylestradiol-Induced Liver Cholestasis

Hussein

¹

2013

Journal of Medicinal Food

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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 was to investigate anticholestatic activity of resveratrol (RES) against liver cholestasis induced by EE in adult female rats. The daily oral administration of the RES at a concentration of 25 mg/kg body weight for 15 days to rats treated with EE (100 μg/kg body weight for 5 days) resulted in a significant protection against EE-induced decrease in both serum cholesterol and bile acid levels as well as against an increase of serum bilirubin concentration. The treatment also resulted in a significant increase in hepatic superoxide dismutase, glutathione peroxidase, glutathione reductase, and catalase activities as well as hepatic protein-bound and nonprotein sulfhydryl groups. RES inhibited serum alkaline phosphatase, alanine aminotransferase, pi-glutathione-S-transferase, gamma-glutamyl transpeptidase, and alpha-glutathione-S-transferase activities, as well as reduced serum tumor necrosis factor-alpha, nitric oxide, and hepatic malondialdehyde as compared to EE-treated rats. The results clearly suggest that RES has a powerful prophylactic action in cholestasis induced by EE. Taken together, RES has potential as a preventive and therapeutic agent for cholestasis and deserves clinical trial in the near future as an adjuvant therapy in women treated with estrogen.

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Effect of 17?-ethinylestradiol on activity of rat liver enzymes for synthesis and hydrolysis of cholesterol esters

Cited by 3 publications

References 12 publications

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

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

Resveratrol Nanoemulsion: A Promising Protector Against Ethinylestradiol-Induced Hepatic Cholestasis in Female Rats

Prophylactic Effect of Resveratrol Against Ethinylestradiol-Induced Liver Cholestasis

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