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Fluvastatin reduced liver injury in rat model of extrahepatic cholestasis

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Abstract

Inhibitors of 3-hydroxy-3methylglutarly coenzyme A, reductase, namely statins, exert pleiotropic actions beyond lipid-lowering effects. In ex vivo and in vitro studies, statins have antioxidative and antiinflammatory effects. Herein, we sought to determine whether treatment with fluvastatin (FV) would be beneficial in a rat model of common bile duct ligation (BDL)-induced liver injury. Female rats were subjected to a sham (n = 10) or BDL (n = 20). Obstructive jaundice was induced in rats by the ligation and division of the common bile duct. Three days after operation, rats subjected to CBDL were randomized to receive treatment with either FV (10 mg/kg) or saline every day over a 10 days experimental period. High levels of alanine aminotransferase, aspartate aminotransferase, and gamma glutamyltransferase decreased significantly (P < 0.05) in animals treated with FV with compared to saline-administrated BDL animals. Compared with sham-operated rats, CBDL rats showed significantly higher levels of total nitrite and nitrate, malondihaldehyde, tumor necrosis factor alpha, myeloperoxidase, and lower concentrations of glutathione, superoxide dismutase, and catalase in the liver tissue (P < 0.001). All of these changes were significantly attenuated (P < 0.05) by treatment with FV after CBDL. CBDL was associated with increased apoptosis and nuclear factor kappa beta expression in saline-treated rats. Treatment with FV also decreased these parameters. These data support the view that FV ameliorates hepatic inflammation, lipid peroxidation, and tissue injury in rats subjected to CDBL. FV warrants further evaluation as an adjunctive treatment to ameliorate liver injury from extrahepatic biliary obstruction.

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Authors and Affiliations

  1. Department of Pediatric Surgery, Turgut Özal Medical Center, İnönü University School of Medicine, Malatya, Turkey

    Savaş Demirbilek, Erkan Tas, Kubilay Gurunluoglu, Melih Akin & Rauf T. Aksoy

  2. Department of Physiology, Turgut Özal Medical Center, İnönü University School of Medicine, Malatya, Turkey

    Memet H. Emre

  3. Department of Pathology, Turgut Özal Medical Center, İnönü University School of Medicine, Malatya, Turkey

    Nasuhi E. Aydin & Nilufer Ozatay

  4. Department of Microbiology, Turgut Özal Medical Center, İnönü University School of Medicine, Malatya, Turkey

    Selma Ay

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  1. Savaş Demirbilek
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Correspondence to Savaş Demirbilek.

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Demirbilek, S., Tas, E., Gurunluoglu, K. et al. Fluvastatin reduced liver injury in rat model of extrahepatic cholestasis. Pediatr Surg Int 23, 155–162 (2007). https://doi.org/10.1007/s00383-006-1829-y

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