{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T06:42:52Z","timestamp":1784616172510,"version":"3.55.0"},"reference-count":56,"publisher":"BMJ","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"published-print":{"date-parts":[[2002,7]]},"abstract":"<jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    Tauroursodeoxycholate (TUDC) provides partial protection against taurolithocholate (TLC) induced cholestasis, possibly by inducing a signalling cascade activating protein kinase C (PKC). The potential protective effects of \u03b2 muricholic acid (\u03b2-MC), another 7-\u03b2-hydroxylated bile salt, have not previously been studied in TLC cholestasis.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Aims:<\/jats:bold>\n                    To study the effect of \u03b2-MC on TLC induced cholestasis and also to investigate further the effects of agents affecting intracellular signalling, notably DBcAMP (a cell permeable cAMP analogue) and several protein kinase inhibitors.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    Functional studies were carried out analysing the proportion of hepatocyte couplets able to accumulate the fluorescent bile acid analogue cholyl-lysyl-fluorescein (CLF) into their sealed canalicular vacuole (cVA of CLF assay).\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    It was found that both \u03b2-MC and DBcAMP were as effective as TUDC in protecting against TLC induced cholestasis. The PKC inhibitors staurosporin and H7 but not the specific protein kinase A (PKA) inhibitor KT5720 abolished the protective effects of TUDC and \u03b2-MC. BAPTA\/AM, a chelator of intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    , significantly decreased the protective effect of both bile salts, and that of DBcAMP. PKC and PKA inhibitors had no effect on protection with DBcAMP.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusions:<\/jats:bold>\n                    \u03b2-MC was as effective as TUDC in protecting against TLC cholestasis. Mobilisation of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    and activation of PKC, but not of PKA, are involved in the anticholestatic effect of the two 7-\u03b2-hydroxylated bile salts. The hepatoprotective effects of DBcAMP involved Ca\n                    <jats:sup>2+<\/jats:sup>\n                    mobilisation, but not PKC or PKA activation.\n                  <\/jats:p>","DOI":"10.1136\/gut.51.1.113","type":"journal-article","created":{"date-parts":[[2002,7,28]],"date-time":"2002-07-28T19:09:06Z","timestamp":1027883346000},"page":"113-119","source":"Crossref","is-referenced-by-count":31,"title":["Hepatoprotection with tauroursodeoxycholate and \u03b2 muricholate against taurolithocholate induced cholestasis: involvement of signal transduction pathways"],"prefix":"10.1136","volume":"51","author":[{"given":"P","family":"Milkiewicz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M 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