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 R.
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 - 2007/3
Y1 - 2007/3
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
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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
SN - 0815-9319
VL - 22
SP - 406
EP - 413
JO - Journal of Gastroenterology and Hepatology (Australia)
JF - Journal of Gastroenterology and Hepatology (Australia)
IS - 3
ER -