title: Homocysteine alterations in experimental cholestasis and its subsequent cirrhosis.
abstract: Homocysteine (Hcy), an intermediate in methionine metabolism, has been proposed to be involved in hepatic fibrogenesis. Impaired liver function can alter Hcy metabolism. The aim of the present study was to determine plasma Hcy alterations in acute obstructive cholestasis and the subsequent biliary cirrhosis. Cholestasis was induced by bile duct ligation and sham-operated and unoperated rats were used as controls. The animals were studied on the days 7th, 14th, 21st and 28th after the operation. Plasma Hcy, cysteine, methionine, nitric oxide (NO) and liver S-adenosyl-methionine (SAM), S-adenosyl-homocysteine (SAH), SAM to SAH ratio and glutathione were measured. Chronic L-NAME treatment was also included in the study. Plasma Hcy concentrations were transiently elevated by the day 14th after bile duct ligation (P < 0.01) and subsequently returned to control levels. Similar relative fluctuations in plasma Hcy were observed in BDL rats after intraperitoneal methionine overload. Plasma methionine, cysteine and nitrite and nitrate were significantly increased after bile duct ligation. SAM to SAH ratio was diminished by the 1st week of cholestasis and remained significantly decreased throughout the study. These events were accompanied by a decrease in GSH to GSSG ratio in the liver. Chronic L-NAME treatment improved SAM to SAH ratio and prevented the elevation of plasma Hcy and methionine (P < 0.05) while couldn't influence the other parameters. In conclusion, this study demonstrates alterations in plasma Hcy and liver SAM and SAH contents in precirrhotic stages and in secondary biliary cirrhosis, for the first time. In addition, we observed that plasma Hcy concentrations in BDL rats follow a distinct pattern of alteration from what has been previously reported in other models of cirrhosis. NO overproduction may contribute to plasma Hcy elevation and liver SAM depletion after cholestasis.
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran.
authors.forename: Mohammad R
authors.initials: MR
authors.lastname: Ebrahimkhani
authors.forename: Hamed
authors.initials: H
authors.lastname: Sadeghipour
authors.forename: Mehdi
authors.initials: M
authors.lastname: Dehghani
authors.forename: Samira
authors.initials: S
authors.lastname: Kiani
authors.forename: Seyedmehdi
authors.initials: S
authors.lastname: Payabvash
authors.forename: Kiarash
authors.initials: K
authors.lastname: Riazi
authors.forename: Hooman
authors.initials: H
authors.lastname: Honar
authors.forename: Parvin
authors.initials: P
authors.lastname: Pasalar
authors.forename: Naser
authors.initials: N
authors.lastname: Mirazi
authors.forename: Massoud
authors.initials: M
authors.lastname: Amanlou
authors.forename: Hassan
authors.initials: H
authors.lastname: Farsam
authors.forename: Ahmad R
authors.initials: AR
authors.lastname: Dehpour
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001652:Bile Ducts / Q000601:surgery; D002779:Cholestasis / Q000378:metabolism*; D003545:Cysteine / Q000097:blood; D005978:Glutathione / Q000378:metabolism; D006710:Homocysteine / Q000097:blood / Q000378:metabolism*; D008026:Ligation; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000378:metabolism*; D008297:Male; D008715:Methionine / Q000097:blood / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D012435:S-Adenosylhomocysteine / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000378:metabolism; D013997:Time Factors
chemical_list: D006710:Homocysteine; D009569:Nitric Oxide; D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine; D008715:Methionine; D005978:Glutathione; D003545:Cysteine; D019331:NG-Nitroarginine Methyl Ester