Peroxisome proliferators-activated alpha agonist treatment ameliorates hepatic damage in rats with obstructive jaundice: an experimental study

نویسندگان

  • Mehmet Cindoruk
  • Mustafa Kerem
  • Tarkan Karakan
  • Bulent Salman
  • Okan Akin
  • Murat Alper
  • Ozlem Erdem
  • Selahattin Ünal
چکیده

BACKGROUND Peroxisome proliferators-activated receptor alpha (PPARalpha) activation modulates cholesterol metabolism and suppresses bile acid synthesis. This study aims to evaluate the effect of short-term administration of fenofibrate, a PPARalpha agonist, on proinflammatory cytokines, apoptosis, and hepatocellular damage in cholestasis. METHODS Forty male Wistar rats were randomly divided into four groups: I = sham operated, II = bile duct ligation (BDL), III = BDL + vehicle (gum Arabic), IV = BDL + fenofibrate (100 mg/kg/day). All rats were sacrificed on 7th day after obtaining blood samples and liver tissue. Total bilirubin, aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP), gamma-glutamyl transferase, (GGT), tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), and total bile acid (TBA) in serum, and liver damage scores; portal inflammation, necrosis, bile duct number, in liver tissue were evaluated. Apoptosis in liver was also assessed by immunohistochemical staining. RESULTS Fenofibrate administration significantly reduced serum total bilirubin, AST, ALT, ALP, and GGT, TNF-alpha, IL-1 beta levels, and TBA (P < 0.01). Hepatic portal inflammation, hepatic necrosis, number of the bile ducts and apoptosis in rats with BDL were more prominent than the sham-operated animals (P < 0.01). PPARalpha induction improved all histopathologic parameters (P < 0.01), except for the number of the bile duct, which was markedly increased by fenofibrate therapy (P < 0.01). CONCLUSION Short-term administration of fenofibrate to the BDL rats exerts beneficial effects on hepatocellular damage and apoptosis.

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Author's response to reviews Peroxisome Proliferators-Activated Alpha Agonist Treatment Improves Hepatic Damage in Rats with Title: Obstructive Jaundice: An Experimental Study

First of all, thanks to all reviewers very much for their criticisms. All the questions are answered one by one and the suitable changes are performed in the article as you suggested. You can make the necessary adjustments. Title: Peroxisome Proliferators-Activated Alpha Agonist Treatment Improves Hepatic Damage in Rats with Obstructive Jaundice: An Experimental Study C: criticism A: author's r...

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Author's response to reviews Title: Peroxisome Proliferators-Activated Alpha Agonist Treatment Improves Hepatic Damage in Rats with Obstructive Jaundice: An Experimental Study Authors:

First of all, thanks to all reviewers very much for their criticisms. All the questions are answered one by one and the suitable changes are performed in the article as you suggested. You can make the necessary adjustments. Title: Peroxisome Proliferators-Activated Alpha Agonist Treatment Improves Hepatic Damage in Rats with Obstructive Jaundice: An Experimental Study C: criticism A: author's r...

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Author's response to reviews Peroxisome Proliferators-Activated Alpha Agonist Treatment Improves Hepatic Damage in Rats with Title: Obstructive Jaundice: An Experimental Study Authors:

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عنوان ژورنال:
  • BMC Gastroenterology

دوره 7  شماره 

صفحات  -

تاریخ انتشار 2007