Effects of patulin on adenosine triphosphatase activities in the mouse

Abstract

Patulin (4-hydroxy-4H-furol3,2clpyran-2(6H)-one), a toxic metabolite of various species of Aspergillus and Penicillium, differentially inhibited (in vitro) the Na+K+-activated and the oligomycin-sensitive and insensitive Mg2+-adenosine triphosphatase activities of mouse brain, kidney, and liver fractions containing nerve endings, mitochondria, and endoplasmic reticulum (B), and microsomal preparations (C) from these tissues. A dose-dependent inhibition of Na+K+-ATPase activity in brain and kidney tissue fractions B and C was observed with corresponding ID50 (50% inhibition) values of 3.0 and 3.7 × 10−4m patulin for brain and kidney B fractions and 3.4 and 2.0 × 10−4m patulin for brain and kidney C fractions, respectively. Oligomycin-sensitive mitochondrial Mg2+-ATPase of brain, kidney, and liver also were inhibited by patulin in both preparations but less drastically than by the Na+K+-ATPase system. Oligomycin-insensitive Mg2+ activities of brain and kidney were only slightly affected with computed ID50 values of 1.0 and 2.0 × 10−3m patulin for B fractions and 3.0 and 6.0 × 10−3m patulin for C fractions, respectively. In vivo oligomycin-sensitive Mg2+ ATPase activities in B preparations from liver and kidneys of mice pretreated with 7.5 mg/kg were inhibited 52 and 28%, respectively, after 48 hr. Furthermore, kidney Na+K+-ATPase activity from the same preprations was significantly correspondingly inhibited. Although oligomycin-sensitive and Na+K+-ATPase activities were not affected in brain, oligomycin-insensitive ATPase activity was slightly reduced in vivo. Thus, in vitro and in vivo results suggest possible patulin-mediated effects in the mouse through disruption of adenosine triphosphatase systems.