EFFECTS OF METAL-IONS ON LIPID-PEROXIDATION IN CULTURED RAT HEPATOCYTES LOADED WITH ALPHA-LINOLENIC ACID

We investigated the ability of various redox-active metal ions to indu ce lipid peroxidation in normal and alpha-linolenic acid-loaded (LNA-l oaded) cultured rat hepatocytes. Lipid peroxidation was estimated by t he accumulation of malondialdehyde : medium. At low concentrations, in duction was highest with ferrous ions (Fe), whereas at high concentrat ions, vanadium (V) and copper ions (Cu) had the greatest effect on bot h groups of hepatocytes. With any one of the three metal ions, the ext ent of lipid peroxidation in LNA-loaded hepatocytes was several times greater compared to normal cells. In addition, upon the addition of Fe or V, LNA-loaded hepatocytes were injured whereas normal cells were n ot. The addition of Cu caused substantial cell injury in normal hepato cytes, and even greater injury in LNA-loaded cells. The prevention of lipid peroxidation in LNA-loaded hepatocytes by addition of an antioxi dant like N,N'-diphenyl-p-phenylenediamine (DPPD) almost completely pr evented Fe- and V-induced cell injury, and reduced Cu-induced cell inj ury. alpha-Tocopherol behaved in a way similar to but less effective t han DPPD. (OH)-O-. radical scavengers such as mannitol and dimethyl su lfoxide (DMSO) had no effect on lipid peroxidation induced by any meta l ions in LNA-loaded hepatocytes. Addition oi cadmium ions (Cd), which required the lowest concentration to cause cell injury, induced a sli ght increase in lipid peroxidation in normal hepatocytes, but did nor induce lipid peroxidation to the same extent as seen in LNA-loaded cel ls treated with any of the three metal ions already mentioned. The inh ibition oi lipid peroxidation by DPPD scarcely protected LNA-loaded he patocytes from Cd-induced cell injury. None of the other metal ions in cluding aluminum (Al), chromium (Cri, manganese (Mn), nickel (Ni), lea d (Pb), and tin (Sn) ions, effectively induced lipid peroxidation in e ither group of hepatocytes, except cobalt ions (Go), which had a perox idative effect in LNA-loaded cells only.