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The effects of N‐acetylcysteine on the expression of matrix metalloproteinase‐2 and tissue inhibitor of matrix metalloproteinase‐2 in hepatic fibrosis in bile duct ligated rats
Author(s) -
Rezaei Arezou,
Ardestani Sussan Kaboudanian,
Forouzandeh Mehdi,
Tavangar Seyed Mohammad,
Khorramizadeh Mohammad Reza,
Payabvash Seyedmehdi,
Nezami Behtash Ghazi,
Jahanshiri Zahra,
Tavakoli Zahra,
Shariftabrizi Ahmad,
Dehpour Ahmad Reza
Publication year - 2008
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/j.1872-034x.2008.00393.x
Subject(s) - acetylcysteine , matrix metalloproteinase , glutathione , reactive oxygen species , lipid peroxidation , oxidative stress , tissue inhibitor of metalloproteinase , chemistry , medicine , endocrinology , fibrosis , liver function , matrix metalloproteinase 3 , biochemistry , biology , antioxidant , enzyme
Aim: N‐acetylcysteine can inhibit the formation of intracellular reactive oxygen intermediates. Cellular redox state plays a role in regulating the secretion of matrix metalloproteinase‐2. We investigated the effects of N‐acetylcysteine on the expression of matrix metalloproteinase‐2 and tissue inhibitor of matrix metalloproteinase‐2. Methods: Bile duct ligated rats were used as a model of hepatic fibrosis. We compared the level of gene expression (using real‐time reverse transcription polymerase chain reaction [RT–PCR]), liver function parameters, hepatic reactive oxygen production, lipid peroxidation and glutathione state in experimental groups. Results: N‐acetylcysteine treatment significantly improved liver function parameters including the plasma levels of aspartate aminotransferase, alkaline phosphatase, gamma‐glutamyl transpeptidase and bilirubin. In addition, significant improvement of glutathione state and reactive oxygen production were observed. Hepatic lipid peroxidation was reversed by N‐acetylcysteine treatment. Although N‐acetylcysteine treatment did not completely normalize the increased matrix metalloproteinase‐2 expression, it significantly decreased its level by 65%. N‐acetylcysteine treatment also significantly decreased matrix metalloproteinase‐2 activity and normalized tissue inhibitor of matrix metalloproteinase‐2 expression. Conclusion: Collectively, N‐acetylcysteine showed inhibition of matrix metalloproteinase‐2 expression and activity. In addition, administration of N‐acetylcysteine was associated with downregulation of the expression of tissue inhibitor of matrix metalloproteinase‐2 and amelioration of oxidative stress in the liver of bile duct ligated rats.