Interaction of secalonic acid D with phenobarbital, 3-methyl cholanthrene, and SKF-525A in mice

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 [ 14 C]SAD with PB and SKF‐525A revealed that although neither PB nor SKF‐525A altered ...