title: Tissue-and metal-specific effects of thiolacrylic acids in rats.
abstract: Kidney copper increased 12- to 18-fold above the normal level in rats administered alpha-mercapto-beta-(2-furyl)acrylic acid (MFA). Kidney zinc increased twofold; plasma zinc increased more than 10-fold and liver zinc increased 30-50%. No other changes in copper, iron, and zinc concentrations were found in these tissues or in bone, brain, heart, lung, skeletal muscle, spleen, or testis. Related compounds produced similar effects, although MFA and its disulfide were the most potent of the compounds tested. These increases in tissue copper and zinc were largely complete after 2-5 d of daily administration of compound. Increased plasma zinc returned toward normal with a half-life of 1.0 d for the process, after dosing was ended; albumin was identified as the species binding the excess zinc in plasma. Kidney copper and zinc, which had increased in the ratio of 3 Cu/Zn, returned to normal levels after dosing was stopped with half-lives of 2.1-2.5 d. Consistent with the observations of highly tissuespecific effects of MFA, copper and zinc balances over 8 weeks of trials were found to be not greatly affected by administration of the compound. Thus, it was not established whether excess metal in affected organs derived from enhanced retention of dietary metal or redistribution from other tissues. Kidney copper and zinc and serum zinc increased even in zinc-deficient rats administered MFA.
authors.affiliation: Merrell Research Center, Merrell Dow Pharmaceuticals, Inc., 45215, Cincinnati, Ohio.
authors.forename: E
authors.initials: E
authors.lastname: Giroux
authors.forename: P J
authors.initials: PJ
authors.lastname: Lachmann
authors.forename: H G
authors.initials: HG
authors.lastname: Petering
authors.forename: N J
authors.initials: NJ
authors.lastname: Prakash
authors.forename: P J
authors.initials: PJ
authors.lastname: Schechter