Homocysteine alterations in experimental cholestasis and its subsequent cirrhosis

Mohammad Ebrahimkhani, Hamed Sadeghipour, Mehdi Dehghani, Samira Kiani, Seyedmehdi Payabvash, Kiarash Riazi, Hooman Honar, Parvin Pasalar, Naser Mirazi, Massoud Amanlou, Hassan Farsam, Ahmad R. Dehpour

Research output: Contribution to journalArticle

14 Citations (Scopus)

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-methonine (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.

Original languageEnglish (US)
Pages (from-to)2497-2512
Number of pages16
JournalLife Sciences
Volume76
Issue number21
DOIs
StatePublished - Apr 8 2005
Externally publishedYes

Fingerprint

Cholestasis
Homocysteine
Fibrosis
Plasmas
Methionine
Liver
Bile Ducts
Ducts
Ligation
Rats
Biliary Liver Cirrhosis
NG-Nitroarginine Methyl Ester
Metabolism
Cysteine
Nitric Oxide
Glutathione Disulfide
Level control
Nitrites
Nitrates
Glutathione

Keywords

  • Cholestasis
  • Cirrhosis
  • Homocysteine
  • Methionine
  • Nitric oxide
  • S-adenosyl-methionine

ASJC Scopus subject areas

  • Pharmacology

Cite this

Ebrahimkhani, M., Sadeghipour, H., Dehghani, M., Kiani, S., Payabvash, S., Riazi, K., ... Dehpour, A. R. (2005). Homocysteine alterations in experimental cholestasis and its subsequent cirrhosis. Life Sciences, 76(21), 2497-2512. https://doi.org/10.1016/j.lfs.2004.12.009

Homocysteine alterations in experimental cholestasis and its subsequent cirrhosis. / Ebrahimkhani, Mohammad; Sadeghipour, Hamed; Dehghani, Mehdi; Kiani, Samira; Payabvash, Seyedmehdi; Riazi, Kiarash; Honar, Hooman; Pasalar, Parvin; Mirazi, Naser; Amanlou, Massoud; Farsam, Hassan; Dehpour, Ahmad R.

In: Life Sciences, Vol. 76, No. 21, 08.04.2005, p. 2497-2512.

Research output: Contribution to journalArticle

Ebrahimkhani, M, Sadeghipour, H, Dehghani, M, Kiani, S, Payabvash, S, Riazi, K, Honar, H, Pasalar, P, Mirazi, N, Amanlou, M, Farsam, H & Dehpour, AR 2005, 'Homocysteine alterations in experimental cholestasis and its subsequent cirrhosis', Life Sciences, vol. 76, no. 21, pp. 2497-2512. https://doi.org/10.1016/j.lfs.2004.12.009
Ebrahimkhani, Mohammad ; Sadeghipour, Hamed ; Dehghani, Mehdi ; Kiani, Samira ; Payabvash, Seyedmehdi ; Riazi, Kiarash ; Honar, Hooman ; Pasalar, Parvin ; Mirazi, Naser ; Amanlou, Massoud ; Farsam, Hassan ; Dehpour, Ahmad R. / Homocysteine alterations in experimental cholestasis and its subsequent cirrhosis. In: Life Sciences. 2005 ; Vol. 76, No. 21. pp. 2497-2512.
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