Microtubule-independent choleresis and anti-cholestatic action of tauroursodeoxycholate in colchicine-treated rat liver.
In order to cast light on the anti-cholestatic and cytoprotective properties of ursodeoxycholic acid (UDCA), intrahepatic transport and secretion of bile salts and biliary phospholipids were investigated by using isolated perfused livers from colchicine-pretreated rats. Administration of taurocholic acid (TCA) after colchicine pretreatment induced marked cholestasis. Tauroursodeoxycholic acid (TUDCA) treatment, in contrast, was associated with maintenance of bile flow, with excretion rates of bile acids and phospholipids similar to those in control animals. Furthermore, TCA-induced cholestasis in colchicine-treated rat livers was clearly decreased by co-administration of TUDCA. Although simultaneous addition of UDCA also showed slight improvement, with or without taurine pre-treatment, biliary bile-salt analysis also showed that cholestasis was markedly remitted as the excretion of taurine-conjugated UDCA was increased. The results suggest that the cytoprotective and anti-cholestatic effects of TUDCA may be linked to action at the intrahepatocyte level, represented by mild detergent effects on organelle lipids and preservation of intracellular transport even under microtubule-dysfunctional conditions. In addition, it was indicated that cytoprotective effects of UDCA may also be exerted after its conjugation with taurine inside hepatocytes.
First Department of Internal Medicine, Nagoya City University, Medical School, Japan.
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T
Nakai
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Katagiri
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M
Hoshino
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Hayakawa
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Ohiwa
D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001646:Bile / Q000378:metabolism*; D002779:Cholestasis / Q000503:physiopathology*; D003078:Colchicine / Q000494:pharmacology*; D008297:Male; D008870:Microtubules / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012636:Secretory Rate / Q000187:drug effects; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology*; D013656:Taurocholic Acid / Q000494:pharmacology; D014580:Ursodeoxycholic Acid / Q000494:pharmacology; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D013655:Taurochenodeoxycholic Acid; D013656:Taurocholic Acid; C031655:ursodoxicoltaurine; D014580:Ursodeoxycholic Acid; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D003078:Colchicine