Research article

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

Mehmet Cindoruk^1* , Mustafa Kerem^2* , Tarkan Karakan¹ , Bulent Salman² , Okan Akin³ , Murat Alper⁴ , Ozlem Erdem⁵ and Selahattin Ünal¹

¹  Department of Gastroenterology, Gazi University Faculty of Medicine, Ankara, Turkey

²  Department of General Surgery, Gazi University Faculty of Medicine, Ankara, Turkey

³  Department of Biochemistry, Kecioren Training and Research Hospital, Ankara, Turkey

⁴  Department of Pathology, Diskapi Training and Research Hospital, Ankara, Turkey

⁵  Department of Pathology, Gazi University Faculty of Medicine, Ankara, Turkey

author email corresponding author email* Contributed equally

BMC Gastroenterology 2007, 7:44doi:10.1186/1471-230X-7-44

Published:	28 November 2007

Abstract

Background

Peroxisome proliferators-activated receptor alpha (PPARα) activation modulates cholesterol metabolism and suppresses bile acid synthesis. This study aims to evaluate the effect of short-term administration of fenofibrate, a PPARα 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 7^th 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-α), interleukin 1 beta (IL-1 β), 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-α, IL-1 β 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). PPARα 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.