Effect of bile acids on the proliferative activity and apoptosis of rat hepatocytes.
Bile acids are known to have damaging as well as protective effects on liver cells. A likely candidate for bile acid-mediated hepatocellular injury during cholestasis is glycochenodeoxycholic acid (GCDCA), a hydrophobic bile acid with a direct cytotoxic effect on hepatocytes. In contrast, ursodeoxycholic acid was shown to exhibit protective effects. Our aim was to determine the effect of GCDCA on proliferation, synthesis and secretion of proteins and death processes in cultured rat hepatocytes. Furthermore, it should be studied whether the hydrophilic bile acid tauroursodeoxycholic acid (TUDCA) might be able to protect cells from the damaging effect of GCDCA. Our results demonstrate that GCDCA decreased dose-dependently hepatocellular proliferation, synthesis and secretion of newly synthesized proteins and, at low concentration, induced apoptosis or, at high doses, cytolysis of cultured hepatocytes. TUDCA did not exert cytotoxic effects on the isolated hepatocytes at a wide range of concentrations. However, TUDCA coincubated with GCDCA protected the cells from the damaging effect of GCDCA at all measured parameters except the secretion of newly synthesized protein.
Danchenko
E
E
Department of Biochemistry, Vitebsk Medical University, Belarus.
Petermann
H
H
Chirkin
A
A
Dargel
R
R
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis / Q000096:biosynthesis; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D005999:Glycochenodeoxycholic Acid / Q000633:toxicity*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D014176:Protein Biosynthesis; D051381:Rats; D017208:Rats, Wistar; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology*; D014580:Ursodeoxycholic Acid / Q000633:toxicity*
D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine; D005999:Glycochenodeoxycholic Acid; D014580:Ursodeoxycholic Acid; D004247:DNA; D007770:L-Lactate Dehydrogenase