Effects of ursodeoxycholate and other bile salts on the levels of rat intestinal alkaline sphingomyelinase: A potential implication in tumorigenesis

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Abstract

Previous studies showed that bile salts had apromoting effect on colon cancer development and thiseffect was inhibited by ursodeoxycholate (UDC). Werecently found that both human colorectal adenomas and carcinomas were associated with a specificdecrease in alkaline sphingomyelinase activity. In thiswork, we compared the effects of ursodeoxycholate andother bile salts on the levels of rat intestinal alkaline sphingomyelinase both in theintestinal loops and after oral administration. Bilesalts at different concentrations were injected intointestinal loops and the dissociation of alkalinesphingomyelinase from the mucosa was assayed. We found that bilesalts, including taurocholate, taurodeoxycholate,glycocholate, glycochenodeoxycholate, and3-(3-cholamidopropyl dimethylammonio)-1-propanesulonate(CHAPS), dose dependently dissociated alkalinesphingomyelinase from the intestinal mucosa. UDC alonedid not dissociate the enzyme but significantlyinhibited the dissociation caused by other bile saltsand CHAPS. Feeding rats with 0.3% (w/w) taurocholate forfour days decreased peak activity of intestinal alkalinesphingomyelinase by 39% and total activity in theintestine by 20% and increased the output of the enzyme in the feces. In contrast, feeding 0.3%(w/w) UDC for four days increased the peak activity ofalkaline sphingomyelinase in the small intestine by 87%and the activity in the colon by 187% . The total activity of alkaline sphingomyelinase wasincreased by 80% and the output of the enzyme in thefeceswas only slightly increased by UDC administration.The changes in alkaline phosphatase after feeding taurocholate and UDC were much smaller. Ourresults indicate that UDC and other bile salts havedifferent effects on the levels of alkalinesphingomyelinase, which may be implicated in theirdifferent influences on cancer development reportedpreviously.

Detaljer

Författare
Externa organisationer
  • Skåne University Hospital
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Farmakologi och toxikologi
Originalspråkengelska
Sidor (från-till)26-32
Antal sidor7
TidskriftDigestive Diseases and Sciences
Volym43
Utgivningsnummer1
StatusPublished - 1998
PublikationskategoriForskning
Peer review utfördJa
Externt publiceradJa