Opioid system blockade decreases collagenase activity and improves liver injury in a rat model of cholestasis

Samira Kiani, Mohammad Ebrahimkhani, Ahmad Shariftabrizi, Behzad Doratotaj, Seyedmehdi Payabvash, Kiarash Riazi, Mehdi Dehghani, Hooman Honar, Alaleh Karoon, Massoud Amanlou, Seyed M. Tavangar, Ahmad R. Dehpour

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Background: Following bile duct ligation (BDL) endogenous opioids accumulate in plasma and play a role in the pathophysiology and manifestation of cholestasis. Evidence of centrally mediated induction of liver injury by exogenous opioid agonist administration, prompts the question of whether opioid receptor blockade by naltrexone can affect cholestasis-induced liver injury. Methods: Cholestasis was induced by BDL and cholestatic and sham-operated rats received either naltrexone or saline for 7 consecutive days. On the 7th day, liver samples were collected for determining matrix metalloproteinase-2 (MMP-2) activity, S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) content and blood samples were obtained for measuring plasma nitrite/nitrate and liver enzyme activities. Results: Naltrexone-treated BDL animals had a significant reduction in plasma enzyme activity and nitrite/nitrate level. Liver SAM: SAH ratio and SAM level improved by naltrexone treatment in cholestatic animals compared to saline-treated BDL ones. Naltrexone treatment in BDL rats led to a decrease in the level of liver MMP-2 activity, which had already increased during cholestasis. Conclusion: Opioid receptor blockade improved the degree of liver injury in cholestasis, as assessed by plasma enzyme and liver MMP-2 activities. The beneficial effect of naltrexone may be due to its ability to increase liver SAM level and restore the SAM: SAH ratio.

Original languageEnglish (US)
Pages (from-to)406-413
Number of pages8
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume22
Issue number3
DOIs
StatePublished - 2007
Externally publishedYes

Fingerprint

Cholestasis
Collagenases
Opioid Analgesics
Naltrexone
S-Adenosylmethionine
Liver
Bile Ducts
Wounds and Injuries
Ligation
S-Adenosylhomocysteine
Matrix Metalloproteinase 2
Opioid Receptors
Nitrites
Nitrates
Enzymes

Keywords

  • Cholestasis
  • Collagenase
  • Endogenous opioids
  • Liver injury
  • Matrix metalloproteinase
  • Nitric oxide
  • S-adenosylhomocysteine
  • S-adenosylmethionine

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

Cite this

Opioid system blockade decreases collagenase activity and improves liver injury in a rat model of cholestasis. / Kiani, Samira; Ebrahimkhani, Mohammad; Shariftabrizi, Ahmad; Doratotaj, Behzad; Payabvash, Seyedmehdi; Riazi, Kiarash; Dehghani, Mehdi; Honar, Hooman; Karoon, Alaleh; Amanlou, Massoud; Tavangar, Seyed M.; Dehpour, Ahmad R.

In: Journal of Gastroenterology and Hepatology (Australia), Vol. 22, No. 3, 2007, p. 406-413.

Research output: Contribution to journalArticle

Kiani, S, Ebrahimkhani, M, Shariftabrizi, A, Doratotaj, B, Payabvash, S, Riazi, K, Dehghani, M, Honar, H, Karoon, A, Amanlou, M, Tavangar, SM & Dehpour, AR 2007, 'Opioid system blockade decreases collagenase activity and improves liver injury in a rat model of cholestasis', Journal of Gastroenterology and Hepatology (Australia), vol. 22, no. 3, pp. 406-413. https://doi.org/10.1111/j.1440-1746.2006.04260.x
Kiani, Samira ; Ebrahimkhani, Mohammad ; Shariftabrizi, Ahmad ; Doratotaj, Behzad ; Payabvash, Seyedmehdi ; Riazi, Kiarash ; Dehghani, Mehdi ; Honar, Hooman ; Karoon, Alaleh ; Amanlou, Massoud ; Tavangar, Seyed M. ; Dehpour, Ahmad R. / Opioid system blockade decreases collagenase activity and improves liver injury in a rat model of cholestasis. In: Journal of Gastroenterology and Hepatology (Australia). 2007 ; Vol. 22, No. 3. pp. 406-413.
@article{c30f9a5b3eed49459a6cff24551e989f,
title = "Opioid system blockade decreases collagenase activity and improves liver injury in a rat model of cholestasis",
abstract = "Background: Following bile duct ligation (BDL) endogenous opioids accumulate in plasma and play a role in the pathophysiology and manifestation of cholestasis. Evidence of centrally mediated induction of liver injury by exogenous opioid agonist administration, prompts the question of whether opioid receptor blockade by naltrexone can affect cholestasis-induced liver injury. Methods: Cholestasis was induced by BDL and cholestatic and sham-operated rats received either naltrexone or saline for 7 consecutive days. On the 7th day, liver samples were collected for determining matrix metalloproteinase-2 (MMP-2) activity, S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) content and blood samples were obtained for measuring plasma nitrite/nitrate and liver enzyme activities. Results: Naltrexone-treated BDL animals had a significant reduction in plasma enzyme activity and nitrite/nitrate level. Liver SAM: SAH ratio and SAM level improved by naltrexone treatment in cholestatic animals compared to saline-treated BDL ones. Naltrexone treatment in BDL rats led to a decrease in the level of liver MMP-2 activity, which had already increased during cholestasis. Conclusion: Opioid receptor blockade improved the degree of liver injury in cholestasis, as assessed by plasma enzyme and liver MMP-2 activities. The beneficial effect of naltrexone may be due to its ability to increase liver SAM level and restore the SAM: SAH ratio.",
keywords = "Cholestasis, Collagenase, Endogenous opioids, Liver injury, Matrix metalloproteinase, Nitric oxide, S-adenosylhomocysteine, S-adenosylmethionine",
author = "Samira Kiani and Mohammad Ebrahimkhani and Ahmad Shariftabrizi and Behzad Doratotaj and Seyedmehdi Payabvash and Kiarash Riazi and Mehdi Dehghani and Hooman Honar and Alaleh Karoon and Massoud Amanlou and Tavangar, {Seyed M.} and Dehpour, {Ahmad R.}",
year = "2007",
doi = "10.1111/j.1440-1746.2006.04260.x",
language = "English (US)",
volume = "22",
pages = "406--413",
journal = "Journal of Gastroenterology and Hepatology (Australia)",
issn = "0815-9319",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Opioid system blockade decreases collagenase activity and improves liver injury in a rat model of cholestasis

AU - Kiani, Samira

AU - Ebrahimkhani, Mohammad

AU - Shariftabrizi, Ahmad

AU - Doratotaj, Behzad

AU - Payabvash, Seyedmehdi

AU - Riazi, Kiarash

AU - Dehghani, Mehdi

AU - Honar, Hooman

AU - Karoon, Alaleh

AU - Amanlou, Massoud

AU - Tavangar, Seyed M.

AU - Dehpour, Ahmad R.

PY - 2007

Y1 - 2007

N2 - Background: Following bile duct ligation (BDL) endogenous opioids accumulate in plasma and play a role in the pathophysiology and manifestation of cholestasis. Evidence of centrally mediated induction of liver injury by exogenous opioid agonist administration, prompts the question of whether opioid receptor blockade by naltrexone can affect cholestasis-induced liver injury. Methods: Cholestasis was induced by BDL and cholestatic and sham-operated rats received either naltrexone or saline for 7 consecutive days. On the 7th day, liver samples were collected for determining matrix metalloproteinase-2 (MMP-2) activity, S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) content and blood samples were obtained for measuring plasma nitrite/nitrate and liver enzyme activities. Results: Naltrexone-treated BDL animals had a significant reduction in plasma enzyme activity and nitrite/nitrate level. Liver SAM: SAH ratio and SAM level improved by naltrexone treatment in cholestatic animals compared to saline-treated BDL ones. Naltrexone treatment in BDL rats led to a decrease in the level of liver MMP-2 activity, which had already increased during cholestasis. Conclusion: Opioid receptor blockade improved the degree of liver injury in cholestasis, as assessed by plasma enzyme and liver MMP-2 activities. The beneficial effect of naltrexone may be due to its ability to increase liver SAM level and restore the SAM: SAH ratio.

AB - Background: Following bile duct ligation (BDL) endogenous opioids accumulate in plasma and play a role in the pathophysiology and manifestation of cholestasis. Evidence of centrally mediated induction of liver injury by exogenous opioid agonist administration, prompts the question of whether opioid receptor blockade by naltrexone can affect cholestasis-induced liver injury. Methods: Cholestasis was induced by BDL and cholestatic and sham-operated rats received either naltrexone or saline for 7 consecutive days. On the 7th day, liver samples were collected for determining matrix metalloproteinase-2 (MMP-2) activity, S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) content and blood samples were obtained for measuring plasma nitrite/nitrate and liver enzyme activities. Results: Naltrexone-treated BDL animals had a significant reduction in plasma enzyme activity and nitrite/nitrate level. Liver SAM: SAH ratio and SAM level improved by naltrexone treatment in cholestatic animals compared to saline-treated BDL ones. Naltrexone treatment in BDL rats led to a decrease in the level of liver MMP-2 activity, which had already increased during cholestasis. Conclusion: Opioid receptor blockade improved the degree of liver injury in cholestasis, as assessed by plasma enzyme and liver MMP-2 activities. The beneficial effect of naltrexone may be due to its ability to increase liver SAM level and restore the SAM: SAH ratio.

KW - Cholestasis

KW - Collagenase

KW - Endogenous opioids

KW - Liver injury

KW - Matrix metalloproteinase

KW - Nitric oxide

KW - S-adenosylhomocysteine

KW - S-adenosylmethionine

UR - http://www.scopus.com/inward/record.url?scp=33846929920&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33846929920&partnerID=8YFLogxK

U2 - 10.1111/j.1440-1746.2006.04260.x

DO - 10.1111/j.1440-1746.2006.04260.x

M3 - Article

C2 - 17295775

AN - SCOPUS:33846929920

VL - 22

SP - 406

EP - 413

JO - Journal of Gastroenterology and Hepatology (Australia)

JF - Journal of Gastroenterology and Hepatology (Australia)

SN - 0815-9319

IS - 3

ER -