Jm. Trivier et al., ANTIOXIDANT DEFENSE CAPACITY MODULATION OF 2 HUMAN CELL-LINES BY AMIODARONE AND DESETHYLAMIODARONE, Toxicology in vitro, 11(3), 1997, pp. 209-216
Although the role of oxidative stress has recently been the subject of
increased discussion in relation to the pathogenesis of amiodarone (A
MIO) toxicity, the cellular mechanisms underlying the hepatic and pulm
onary disorders remain unknown. In order to investigate the effects of
AMIO and its active metabolite desethylamiodarone (DEA) on the cellul
ar antioxidant status, defence capacities of liver and lung cell lines
have been first compared with published data on normal corresponding
cells. Glutathione content, superoxide dismutase (SOD) and glutathione
-related enzymes were then determined in Hep 3B and L132 cells, after
AMIO and DEA treatment. Although no glutathione peroxidase could be de
tected in either cell line, Hep 3B and L132 cells were able to express
normal glutathione S-transferase (GSH-S-T) and glutathione reductase
(GSSG-Rd) activities. The principal targets of AMIO and DEA were, resp
ectively, GSH-S-T and GSSG-Rd in Hep 3B cells, while SOD was significa
ntly decreased by both drugs in L132 cells. Concomitantly, glutathione
status (defined as the ratio of oxidized to total glutathione) was al
tered in Hep 3B but not in L132 cells. These findings suggest that the
first step of amiodarone-induced Hep 3B and L132 cell lesions may res
ult from the overwhelming of their antioxidant defence system. (C) 199
7 Elsevier Science Ltd.