抄録
Anthracyclines have been used to cure a variety of cancers, and they are one of the most effective anti-cancer drugs. However, due to the simultaneous occurrence of serious side effects, successful chemotherapy is difficult to administer in clinical cancer treatment. Therefore, to evaluate the side effects, we examined the influence of anthracycline derivatives, especially epirubicin (EPI), on the glucose secretion and cytotoxicity of anthracycline derivatives in primary culture of rat hepatocytes.
In this study, EPI reduced the spontaneous glucose secretion dose-dependently in a primary culture of rat hepatocytes. However, EPI enhanced the increased-secretion induced by glucagon, and the potency of such enhancement at low concentrations was stronger than that at high concentrations. In contrast, aclarubicin (ACL) reduced both the spontaneous glucose secretion and the increased-secretion. Furthermore, Anthracycline derivatives increased the lactate dehydrogenase (LDH) leakage both time- and dose-dependently, and the potency order was idarubicin≥ACL >daunorubicin> EPI. The degree of cytotoxicity as evaluated by measuring the glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) levels and by performing an MTT-assay was also similar to the results obtained for LDH leakage.
These results suggest that EPI stimulates the sensitivity of rat hepatocytes to other endogenous agents, and this influence may be involved in the degree of cytotoxicity for anthracycline derivatives.
