Utility of human hepatocyte spheroids without feeder cells for evaluation of hepatotoxicity.

Utility of human hepatocyte spheroids without feeder cells for evaluation of hepatotoxicity. J Toxicol Sci. 2017;42(4):499-507 Authors: Ogihara T, Arakawa H, Jomura T, Idota Y, Koyama S, Yano K, Kojima H Abstract We investigated the utility of three-dimensionally cultured hepatocytes (spheroids) without feeder cells (Sph(f-)) for the prediction of drug-induced liver injury (DILI) in humans. Sph(f-) and spheroids cultured on feeder cells (Sph(f+)) were exposed to the hepatotoxic drugs flutamide, diclofenac, isoniazid and chlorpromazine at various concentrations for 14 days, and albumin secretion and cumulative leakages of toxicity marker enzymes, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and γ-glutamyl transpeptidase (γ-GTP), were measured. The cumulative AST, LDH or γ-GTP leakages from Sph(f-) were similar to or greater than those from Sph(f+) for all drugs tested, although ALT leakages showed no consistent difference between Sph(f+) and Sph(f-). In the case of Sph(f-), significant correlations among all the toxicity markers except for γ-GTP were observed. As regards the drug concentrations causing 1.2-fold elevation of enzyme leakage (F1.2), no consistent difference between Sph(f+) and Sph(f-) was found, although several F1.2 values were undetermined, especially in Sph(f+). The IC50 of albumin secretion and F1.2 of AST leakage from Sph(f-) were equal to or lower than those of S...
Source: Journal of Toxicological Sciences - Category: Toxicology Tags: J Toxicol Sci Source Type: research