In vitro effect of chromium and other trace metals on mouse hepatotoxicity induced by carbon tetrachloride exposure

Using primary cultured mouse hepatocytes, in vitro study was performed 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 liver damage induced by CCl4 exposure. 1) The LDH activity 60 min after CCl4 exposure increased dose-dependently with CCl4 concentrations in all of the trace metal pretreatment groups, except for the Cr(VI) pretreatment group, which showed a significant protective effect even after 30 min of CCl4 exposure. 2) LDH leakage was not observed 10 min after CCl4 exposure at 3 or 5 mM, while lipid peroxidation was increased dose-dependently with CCl4 concentrations in all groups except the Cr(VI) pretreatment group, in which the production of peroxidated lipid was significantly inhibited. 3) Similarly to the pretreatment with Cr(VI), LDH leakage 30 min after exposure to 5 mM CCl4 was inhibited by pretreatment with such antioxidants as N,N'-diphenyl-p-phenylenediamine or DL-alpha-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) 10 min 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 hepatotoxicity.