Secondly, numerous flaws are present in study designs
However, since the differences in total GSH conjugation activity catalyzed by these allelic variants are not higher than 30 %, the differences in inactivation of reactive intermediates by hGSTP1-1 are not likely to be a major factor in determining interindividual difference in susceptibility to adverse drug reactions induced by the drugs studied [34]
Indeed, oxidative stress-induced drop of bile flow and/or decrease of the bile salt-secretory rate becomes aparent before leakage of cytosolic hepatocellular enzymes or increments in intracellular GSSG levels is induced by administration of different pro-oxidant compounds to isolated perfused rat livers.70,75 Likewise, in isolated rat hepatocyte couplets, an in vitro model for the study of hepatocanalicular function, the secretion of fluorescent bile-salt analogues into the canalicular vacuole was impaired by low concentrations of the pro-oxidant compounds, tBOOH and 2,3-dimethoxy-1,4-naphthoquinone, even when GSSG intracellular levels and cellular viability were unaffected.98 Finally, also in the couplet model, a dissociation between apical secretion of fluorescent bile-salt analogues and the amount of GSSG produced in the cell by the oxidizing effects of redox-cycling quinones has been reported.99 Overall, these results suggest that more subtle changes in the machinery involved in bile formation occur under mild oxidative stress conditions
(Mitosporic fungi) Chinese caterpillar fungi, Tochukaso
