Effect of penicillic acid on biliary excretion of indocyanine green in the mouse and rat.

Penicillic acid (PA), a mycotoxin, is hepatotoxic. A study was undertaken to investigate its effects on hepatobiliary excretory function, using the anionic compounds indocyanine green (ICG), in mice and rats. Pretreatment with a single dose of PA (90 mg/kg, ip, an LD50 dose in both species) resulted in depression of ICG excretion in both species. This depression was dose- and time-dependent. Decreases of 42 and 57% in biliary excretion of ICG were observed in rats and mice 48 and 72 h after PA pretreatment, respectively. Although bile flow was depressed significantly when expressed in terms of body weight, it was not altered in mice when expressed in terms of liver weight. Bile flow was not affected in rats. While the serum ICG concentration was increased after PA treatment in both species, the liver ICG concentration was not affected. The liver-to-serum, bile-to-serum, and bile-to-liver ICG concentration ratios decreased in PA-treated animals. These data suggest that the PA-induced hepatobiliary excretory dysfunction may result from depression of both uptake of ICG into the liver and bile canlicular transport of ICG.