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Hepatotoxicity of the mycotoxin penicillic acid: A pharmacokinetics consideration
Author(s) -
Chan P. K.,
Hayes A. W.
Publication year - 1981
Publication title -
journal of the american oil chemists' society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.512
H-Index - 117
eISSN - 1558-9331
pISSN - 0003-021X
DOI - 10.1007/bf02679316
Subject(s) - metabolite , chemistry , toxicity , pharmacology , pharmacokinetics , glucuronide , urine , toxicokinetics , active metabolite , oral administration , glutathione , aflatoxin , biochemistry , medicine , enzyme , organic chemistry , food science
The hepatotoxicity of penicillic acid (PA), a carcinogenic mycotoxin, was substantiated by a variety of hepatic functional tests. Involvement of an active metabolite as the toxic species was proposed. The toxicity of PA was dependent on the route of administration with intraperitoneal (ip) being the most toxic followed by intravenous (iv) and oral. This difference in toxicity was explained by the kinetic data for PA if liver were assumed to be the site of activation. One‐, 2‐ and 3‐compartment open models were proposed to fit the plasma parent compound concentration after oral, ip, and iv administration of PA. Liver, kidneys, heart, lungs and spleen contained more radioactivity than brain, fat and muscle after [ 14 C] ‐ PA administration. Only a fraction of the radioactivity in the blood was detected as the parent compound. Most of the recovered radioactivity in the kidneys and liver was in the cytosol fraction. [ 14 C]PA was readily metabolized in the liver. The metabolites were excreted in the bile and effectively cleared by the kidneys. Fecal and respiratory CO 2 were minor excretory routes. Over 90% of the urinary and 99% of the biliary metabolites were not extracted with polar organic solvents. Three water‐soluble metabolites (derived from GSH or cysteine) were resolved by HPLC in urine and bile. About 10% of the urinary metabolites were detected as glucuronide conjugates. These data supported the hypothesis that an active metabolite which can be detoxified by GSH is involved in the toxicity of PA.