Effects of dietary lipid peroxidation products on hormonal responses in primary cultured hepatocytes of rats.

Dietary lipid peroxidation products cause endogenous lipid peroxidation with hepatic dysfunction. In this study, we isolated and cultured hepatocytes of rats that were given secondary autoxidation products of linoleic acid (p.o., 400 mg/rat/day for 3 days), and examined the hormonal responses of these hepatocytes. An increase in thiobarbituric acid reactive substances and a depletion of vitamin E persisted in hepatocytes from treated rats for at least 24 h in culture as compared to those from control rats. As markers for hepatic dysfunction, the activities of six enzymes were measured. In each case, there was an initial decrease in the enzyme activity in hepatocytes from the treated rats, and all activities were restored by 48 h in culture. Then, we measured the hormonal responses of these hepatocytes. The responses to insulin or glucagon in hepatocytes from secondary products-treated and control rats were the same. In contrast, the response to dexamethasone was significantly lowered in hepatocytes from secondary products-treated rats as measured by the induction of tryptophan 2,3-dioxygenase and tyrosine aminotransferase. We conclude that primary cultured hepatocytes from the rats treated in vivo with dietary lipid peroxidation products retained symptoms of oxidative stress and had a low response to glucocorticoids.