title: Protective effect of Jasonia montana against ethinylestradiol-induced cholestasis in rats.
abstract: 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.
authors: Department of Biochemistry, Faculty of Pharmacy, October 6th University, Cairo, Egypt.
authors: Mohammed A
authors: MA
authors: Hussein
authors: Soad M
authors: SM
authors: Abdel-Gawad
keywords: Ethinylestradiol; GPx; Hepatic total; Jasonia montana; MDA; Pi-GST; Protein-bound and non-protein sulfhydryl groups; SOD; TNF-α
references: Am J Gastroenterol. 1982 Jun;77(6):397-400
references: 6979924
references: J Hepatol. 1997 Aug;27(2):363-70
references: 9288612
references: Biochemistry. 1988 May 31;27(11):3939-46
references: 3415965
references: Life Sci. 1999;65(4):337-53
references: 10421421
references: J Pharm Pharmacol. 1998 Jul;50(7):789-94
references: 9720629
references: Transplant Proc. 1997 Nov;29(7):2827-9
references: 9365578
references: Biochem Pharmacol. 1992 Mar 17;43(6):1289-93
references: 1562282
references: Clin Chem. 1969 Feb;15(2):124-36
references: 5773262
references: Diabetes. 1996 Feb;45(2):183-9
references: 8549863
references: Biull Eksp Biol Med. 1986 Aug;102(8):162-4
references: 3091113
references: J Biol Chem. 1951 Nov;193(1):265-75
references: 14907713
references: J Hepatol. 1999 Feb;30(2):311-20
references: 10068112
references: Biochem J. 1978 Jul 15;174(1):45-51
references: 697762
references: Semin Liver Dis. 1987 Feb;7(1):8-23
references: 3296217
references: J Lab Clin Med. 1967 Jul;70(1):158-69
references: 6066618
references: Eur J Gastroenterol Hepatol. 1998 Jul;10(7):539-41
references: 9855073
references: J Surg Res. 1997 Oct;72(2):129-34
references: 9356233
references: Annu Rev Physiol. 1995;57:737-69
references: 7539995
references: J Clin Invest. 1993 Jun;91(6):2714-20
references: 8514879
references: Cell Biophys. 1989 Apr;14(2):175-85
references: 2472207
references: Biochem J. 1992 Jun 15;284 ( Pt 3):905-10
references: 1622406
references: Mutat Res. 1988 Dec;202(2):363-75
references: 3057367
references: J Biol Chem. 1979 Nov 25;254(22):11360-6
references: 227867
references: J Pharm Sci. 1966 Mar;55(3):225-76
references: 5335471
references: Gut. 1997 Aug;41(2):138-41
references: 9301489
references: Gastroenterology. 1995 Oct;109(4):1249-56
references: 7557092
references: J Nutr. 2001 Nov;131(11):2932-5
references: 11694621
references: Am J Physiol. 1996 Dec;271(6 Pt 1):G1043-52
references: 8997249
references: Anal Biochem. 1968 Oct 24;25(1):192-205
references: 4973948
references: Nat Prod Res. 2005 Apr;19(3):253-65
references: 15702639
references: J Hepatol. 1997 Jan;26(1):146-57
references: 9148006
references: Toxicol Appl Pharmacol. 1994 Dec;129(2):207-13
references: 7992311
references: Clin Chem. 1981 Aug;27(8):1352-6
references: 6895053
references: Clin Chem. 1995 Jun;41(6 Pt 1):892-6
references: 7768008
references: Am J Physiol Gastrointest Liver Physiol. 2003 Nov;285(5):G1004-13
references: 12791596
references: Hepatology. 1992 Jul;16(1):217-23
references: 1618473
references: Toxicol Sci. 2002 Feb;65(2):166-76
references: 11812920
references: Vet Rec. 1986 Nov 22;119(21):519-22
references: 3811158
references: Planta Med. 1993 Feb;59(1):68-70
references: 8441785
references: Cancer. 1991 Mar 15;67(6):1608-13
references: 2001549
references: Biochemistry. 1986 Apr 8;25(7):1632-6
references: 3707898
references: J Ethnopharmacol. 2000 Jul;71(1-2):23-43
references: 10904144
references: Clin Exp Pharmacol Physiol. 2001 Aug;28(8):637-42
references: 11473529
references: Pharmacol Res. 1997 Sep;36(3):243-7
references: 9367670
references: Comp Biochem Physiol C Toxicol Pharmacol. 2000 Jun;126(2):105-11
references: 11050682
references: Free Radic Biol Med. 1991;11(1):81-128
references: 1937131
references: Am J Gastroenterol. 2000 May;95(5):1130-8
references: 10811317
references: J Lipid Res. 1996 Aug;37(8):1812-22
references: 8864965