Lipid peroxidation and cellular damage caused by the pyrrolizidine alkaloid senecionine, the alkenal trans-4-hydroxy-2-hexenal, and related alkenals.

Lipid peroxidation was examined as a possible mechanism for cell injury by trans-4-OH-2-hexenal, the macrocyclic pyrrolizidine alkaloid senecionine and related alkenals in isolated rat hepatocytes. Each compound elicited a positive dose response for peroxidation of cellular lipids as measured by the formation of thiobarbituric acid-reactive products. The addition of the anti-oxidant N,N'-diphenyl-p-phenylenediamine to the hepatocyte suspensions inhibited the production of thiobarbituric acid-reactants. However, the presence of the anti-oxidant had no protective effects on the cell membrane integrity as evidenced by the leakage of lactate dehydrogenase from the cells into the surrounding media. These results suggest that lipid peroxidation which occurs in the presence of senecionine, trans-4-OH-2-hexenal or related alkenals is not entirely responsible for the cellular damage in isolated rat hepatocytes.