ABSTRACT
We investigated the ability of various redox-active metal ions to induce lipid peroxidation in normal and alpha-linolenic acid-loaded (LNA-loaded) cultured rat hepatocytes. Lipid peroxidation was estimated by the accumulation of malondialdehyde (MDA) in the culture medium. At low concentrations induction was highest with ferrous ions (Fe), whereas at high concentrations, vanadium (V) and copper ions (Cu) had the greatest effect on both groups of hepatocytes. With any one of the three metal ions, the extent 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 not. The addition of Cu caused substantial cell injury in normal hepatocytes, and even greater injury in LNA-loaded cells. The prevention of lipid peroxidation in LNA-loaded hepatocytes by addition of an antioxidant like N,N'-diphenyl-p-phenylene-diamine (DPPD) almost completely prevented Fe- and V-induced cell injury, and reduced Cu-induced cell injury. alpha-Tocopherol behaved in a way similar to but less effective than DPPD. .OH radical scavengers such as mannitol and dimethyl sulfoxide (DMSO) had no effect on lipid peroxidation induced by any metal ions in LNA-loaded hepatocytes. Addition of cadmium ions (Cd), which required the lowest concentration to cause cell injury, induced a slight increase in lipid peroxidation in normal hepatocytes, but did not induce lipid peroxidation to the same extent as seen in LNA-loaded cells treated with any of the three metal ions already mentioned. The inhibition of lipid peroxidation by DPPD scarcely protected LNA-loaded hepatocytes from Cd-induced cell injury. None of the other metal ions including aluminum (Al), chromium (Cr), manganese (Mn), nickel (Ni), lead (Pb), and tin (Sn) ions, effectively induced lipid peroxidation in either group of hepatocytes, except cobalt ions (Co), which had a peroxidative effect in LNA-loaded cells only.