Reddy C S, Reddy R V, Hayes A W
J Toxicol Environ Health. 1983 Oct-Dec;12(4-6):687-94. doi: 10.1080/15287398309530460.
Secalonic acid D (SAD) is an acutely toxic and teratogenic fungal metabolite produced by Penicillium oxalium in corn and other cereal grains. Experiments were conducted to study the effects of single and multiple doses of SAD on pentobarbital-induced narcosis, as an index of the modulating effect of SAD on the hepatic drug metabolizing enzymes in mice. The effects of known enzyme modulators-phenobarbital (PB), 3-methyl cholanthrene (3-MC), and diethylaminoethyl diphenylproply acetate hydrochloride (SKF-525A)-on the acute toxicity of SAD in mice were also studied using body weights, mortality, and histopathology as indices. Results of this study failed to demonstrate any modulating effect by SAD of pentobarbital metabolizing enzymes. Pretreatment with SKF-525A, an enzyme inhibitor, enhanced SAD toxicity in mice, whereas pretreatment with PB or 3-MC, known enzyme inducers, had no effect. Further studies of interaction of [14C]SAD with PB and SKF-525A revealed that although neither PB nor SKF-525A altered the ratio of parent compound to total metabolites excreted in bile, SKF-525A significantly reduced the bile flow as well as the elimination of SAD-derived radioactivity in bile. These results strongly suggest the possibility that the effects of SKF-525A, other than the enzyme inhibition, may be responsible for its enhancement of SAD toxicity in mice.
七叶灵酸D（SAD）是一种由草酸青霉在玉米和其他谷物中产生的具有急性毒性和致畸性的真菌代谢产物。进行实验以研究单剂量和多剂量SAD对戊巴比妥诱导的麻醉的影响，以此作为SAD对小鼠肝脏药物代谢酶调节作用的指标。还以体重、死亡率和组织病理学为指标，研究了已知的酶调节剂——苯巴比妥（PB）、3-甲基胆蒽（3-MC）和盐酸二乙氨基乙基二苯基丙酯（SKF-525A）对SAD在小鼠体内急性毒性的影响。本研究结果未能证明SAD对戊巴比妥代谢酶有任何调节作用。用酶抑制剂SKF-525A预处理可增强SAD对小鼠的毒性，而用已知的酶诱导剂PB或3-MC预处理则没有效果。对[14C]SAD与PB和SKF-525A相互作用的进一步研究表明，虽然PB和SKF-525A都没有改变胆汁中母体化合物与总代谢产物的比例，但SKF-525A显著降低了胆汁流量以及胆汁中SAD衍生放射性物质的消除。这些结果有力地表明，SKF-525A除了酶抑制作用外，其作用可能是导致其增强SAD对小鼠毒性的原因。
