Comparative cytotoxic and cytoprotective effects of taurohyodeoxycholic acid (THDCA) and tauroursodeoxycholic acid (TUDCA) in HepG2 cell line.
This study was performed to compare the effects of two hydrophilic bile acids, taurohyodeoxycholic acid (THDCA) and tauroursodeoxycholic acid (TUDCA), on HepG2 cells. Cytotoxicity was evaluated at different times of exposure by incubating cells with increasing concentrations (50-800 micromol/l) of either bile acid, while their cytoprotective effect was tested in comparison with deoxycholic acid (DCA) (350 micromol/l and 750 micromol/l)-induced cytotoxicity. Culture media, harvested at the end of each incubation period, were analyzed to evaluate aspartate transaminase (AST), alanine transaminase and gamma-glutamyltranspeptidase release. In addition, the hemolytic effect of THDCA and TUDCA on human red blood cells was also determined. At 24 h of incubation neither THDCA nor TUDCA was cytotoxic at concentrations up to 200 and 400 micromol/l. At 800 micromol/l both THDCA and TUDCA induced a slight increase in AST release. At this concentration and with time of exposure prolonged up to 72 h, THDCA and TUDCA induced a progressive increase of AST release significantly (P<0.05) higher than that of controls being AST values for THDCA (2.97+/-0.88 time control value (tcv) at 48 h and 4.50+/-1.13 tcv at 72 h) significantly greater than those of TUDCA (1.50+/-0.20 tcv at 48 h and 1.80+/-0.43 tcv at 72 h) (P<0.01). In cytoprotection experiments, the addition of 50 micromol/l THDCA decreased only slightly (-5%) AST release induced by 350 micromol/l DCA, while the addition of 50 micromol/l TUDCA was significantly effective (-23%; P<0.05). Higher doses of THDCA or TUDCA did not reduce toxicity induced by 350 micromol/l DCA, but were much less toxic than an equimolar dose of DCA alone. At the concentration used in this experimental model neither THDCA nor TUDCA was hemolytic; however at a very high concentration (6 mmol/l) both bile acids induced 5-8% hemolysis. We conclude that bile acid molecules with a similar degree of hydrophilicity may show different cytotoxic and cytoprotective properties.
Carubbi
Francesca
F
Dipartimento di Medicina Interna, Università degli Studi di Modena e Reggio Emilia, Policlinico, Via del Pozzo 71, 41100 Modena, Italy.
Guicciardi
Maria Eugenia
ME
Concari
Mauro
M
Loria
Paola
P
Bertolotti
Marco
M
Carulli
Nicola
N
D000410:Alanine Transaminase / Q000032:analysis; D001219:Aspartate Aminotransferases / Q000032:analysis; D003840:Deoxycholic Acid / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis; D006801:Humans; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology* / Q000633:toxicity; D013657:Taurodeoxycholic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000633:toxicity; D013997:Time Factors; D011503:Transglutaminases / Q000032:analysis; D014407:Tumor Cells, Cultured / Q000187:drug effects
D003840:Deoxycholic Acid; C083510:taurohyodeoxycholic acid; D013655:Taurochenodeoxycholic Acid; D013657:Taurodeoxycholic Acid; C031655:ursodoxicoltaurine; D011503:Transglutaminases; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase