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


CONCLUSIONS
Short-term administration of fenofibrate to the BDL rats exerts beneficial effects on hepatocellular damage and apoptosis.
Department of Gastroenterology, Gazi University Faculty of Medicine, Ankara, Turkey. mcindoruk@gazi.edu.tr
Mehmet
M
Cindoruk
Mustafa
M
Kerem
Tarkan
T
Karakan
Bulent
B
Salman
Okan
O
Akin
Murat
M
Alper
Ozlem
O
Erdem
Selahattin
S
Unal
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001652:Bile Ducts; D001663:Bilirubin / Q000097:blood; D002779:Cholestasis / Q000150:complications; D016207:Cytokines / Q000097:blood; D011345:Fenofibrate / Q000494:pharmacology*; D022781:Hepatocytes; D018836:Inflammation Mediators / Q000097:blood; D041781:Jaundice, Obstructive / Q000209:etiology / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D008026:Ligation; D008099:Liver / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D047493:PPAR alpha / Q000819:agonists*; D051381:Rats; D017208:Rats, Wistar
D016207:Cytokines; D018836:Inflammation Mediators; D047493:PPAR alpha; D008315:Malondialdehyde; D001663:Bilirubin; D011345:Fenofibrate