Acute Toxicity of Chloropeptide, a Hepatotoxic Metabolite of Penicillium Islandicum Sopp

Chlorine-containing cyclic pentapeptide (Cl-peptide) is one of the hepatotoxic and hepatocarcinogenic metabolites of Penicillium islandicum Sopp. The sc LD<50> values of Cl-peptide for mice, rats and guinea-pigs were all in the range of 0.5 mg/kg, while the po LD<50> values for mice and rats were around 5mg/kg. The newborn mice were less susceptible than the adults. The acutely intoxicated mice and rats showed a marked elevation of serum transaminases and a transient increment followed by a marked decline of blood glucose level. The liver of animals pretreated with the toxin showed marked declines of glycogen and microsomal protein and an increase of cyclic AMP content. Tracer experiments revealed a preferencial accumulation of the toxin in the liver of mice and an excretion through feces. Correlation between the hepatotoxicity and the hepato-accumulation of the cyclic peptide was discussed.