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Tsuboi K, Tazuma S, Ochi H, et al. Hydrophilic bile salts have a cytoprotective effect against cyclosporine A-induced cholestasis through enhanced canalicular membrane fluidity and transporter activity. Hepatol Res. 2003;25(1):38-47doi: 10.1016/s1386-6346(02)00170-5.
Tsuboi, K., Tazuma, S., Ochi, H., & Chayama, K. (2003). Hydrophilic bile salts have a cytoprotective effect against cyclosporine A-induced cholestasis through enhanced canalicular membrane fluidity and transporter activity. Hepatology research : the official journal of the Japan Society of Hepatology, 25(1), 38-47. https://doi.org/10.1016/s1386-6346(02)00170-5
Tsuboi, Kazuhiko, et al. "Hydrophilic bile salts have a cytoprotective effect against cyclosporine A-induced cholestasis through enhanced canalicular membrane fluidity and transporter activity." Hepatology research : the official journal of the Japan Society of Hepatology vol. 25,1 (2003): 38-47. doi: https://doi.org/10.1016/s1386-6346(02)00170-5
Tsuboi K, Tazuma S, Ochi H, Chayama K. Hydrophilic bile salts have a cytoprotective effect against cyclosporine A-induced cholestasis through enhanced canalicular membrane fluidity and transporter activity. Hepatol Res. 2003 Jan;25(1):38-47. doi: 10.1016/s1386-6346(02)00170-5. PMID: 12644037.
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Hepatol Res. 2003 Jan;25(1):38-47. doi: 10.1016/s1386-6346(02)00170-5.

Hydrophilic bile salts have a cytoprotective effect against cyclosporine A-induced cholestasis through enhanced canalicular membrane fluidity and transporter activity.

Hepatology research : the official journal of the Japan Society of Hepatology

Kazuhiko Tsuboi, Susumu Tazuma, Hidenori Ochi, Kazuaki Chayama

Affiliations

  1. First Department of Internal Medicine, Hiroshima University School of Medicine, 1-2-3, Kasumi, Minami-ku, 734-8551, Hiroshima, Japan

PMID: 12644037 DOI: 10.1016/s1386-6346(02)00170-5

Abstract

Cyclosporine A (CsA) reduces liver canalicular membrane (CM) fluidity to cause a disproportionate reduction of biliary lipid secretion (the uncoupling phenomenon) without affecting adenosine triphosphate-dependent (ABC) transporters except for Mdr1. This study investigated whether hydrophilic bile salts inhibit CsA-induced cholestasis, focusing on CM fluidity and ABC transporter expression. Male Sprague-Dawley rats were infused with taurocholate (TC) (200 nmol/min/100 g body weight) for 2 h, flowed by infusion with tauroursodeoxycholate (TUDC), tauroalphamuricholate, or taurobetamuricholate (100 nmol/min/100 g body weight plus TC at 100 nmol/min/100 g body weight). Thereafter, CsA (20 mg/kg body weight) was injected as a bolus and bile was collected for 2 h. Canalicular membrane vesicles were prepared for analysis of cholesterol (CH), phospholipid (PL), CM fluidity, and expression of ABC transporters (Mdr1, Bsep, Mdr2, and Mrp2). CsA administration reduced biliary lipid secretion along with a disproportionately smaller decline of bile salt secretion. Hydrophilic bile salts significantly inhibited cholestasis after CsA injection by increasing CM fluidity and by increasing the expression of Mrp2 and Bsep, whereas Mdr1 and Mdr2 were unaltered. (1) Hydrophilic bile salts inhibit CsA-induced cholestasis, presumably by increasing CM fluidity, and this action was greatest with TUDC. (2) The fact that ABC transporters, except for Mdr1 and Mdr2, were overexpressed in the CM after infusion of these bile salts suggests that cytoprotective bile salts functions may increase transporter mass as well as enhancing transporter activity.

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