M. Tezuka et al., IN-VITRO EFFECT OF CHROMIUM AND OTHER TRACE-METALS ON MOUSE HEPATOTOXICITY INDUCED BY CARBON-TETRACHLORIDE EXPOSURE, Biological & pharmaceutical bulletin, 18(2), 1995, pp. 256-261
Using primary cultured mouse hepatocytes , in vitro study was performe
d to discuss the effect of Cr(III) and several other trace metals, Cr(
VI), Mn(II), Zn(II), Co(II), Cu(II), Ni(II), and Ga(III) on acute live
r damage induced by CCl4 exposure. 1) The LDH activity 60min after CCl
4 exposure increased dose-dependently with CCl4 concentrations in all
of the trace metal pretreatment groups, except for the Cr(VI) pretreat
ment group, which showed a significant protective effect even after 30
min of CCl4 exposure. 2) LDH leakage was not observed 10min after CCl
4 exposure at 3 or 5 mM, while Lipid peroxidation was increased dose-d
ependently with CCl4 concentrations in all groups except the Cr(VI) pr
etreatment group, in which the production of peroxidated lipid was sig
nificantly inhibited. 3) Similarly to the pretreatment with Cr(VI), LD
H leakage 30min after exposure to 5mM CCl4 was inhibited by pretreatme
nt with such antoxidants as N,N'-diphenyl-p-phenylenediamine or DL-alp
ha-tocopherol. 4) The Cr(VI) uptake was about 50% of the added amount,
whereas the Cr(III) uptake was only 5% of the added amount. 5) 90% or
more of the intracellular chromium was reduced to Cr(III) 10min after
Cr(VI) treatment. The results suggested that the in vitro protective
effect of pretreatment with Cr(VI) was due to a rapid reduction of Cr(
VI) to Cr(III), and the radical scavenger-like effect of the produced
Cr(III) was the same effect as in vivo Cr(III); it therefore suggests
that Cr(III) contributes to protective effect on CCl4-induced hepatoto
xicity.