Mercapturic acid effects

Biomarkers of Exposure and Effect. The presence of thiocyanate and 2-cyanoethyl mercapturic acid have been monitored in urine as indicators of acrylonitrile exposure. 

L-2-oxothiazolidine-4-carboxylic acid, on the urinary elimination of mercapturic acids of ethylene oxide, dibromoethane, and acrylonitrile A dose-effect study. Can J Physiol Pharmacol 67 207-212. 

Burka et al. (1994) examined the effect of treatment of rats with phenobarbital and SKF-525A on the urinary metabolite profile of [2- - C]aciy lonitnle. Phenobarbital treatment increased the excretion of products attributed to the oxidation of acrylonitrile to CEO, while SKF-525A treatment enhanced the excretion of the mercapturic acid derived from the glutathione conjugation of acrylonitrile itself. 

Defatting creates cell necrosis. Nematocides also reduce cell P450 content. Sulphyril, but not glutathione, mediates toxic effects. Biotransformation (hydrolysis and oxidation) is via the mercapturic acid route, producing a-chlorohydrin and a-bromohy-drin, two antifertility agents. Further oxidation of these substances may produce oxalic acid, which causes liver and kidney damage. 

A phase Ila clinical trial was conducted with 230 residents of Daxin, Qidong County of Jiangsu Province, China [65]. Daily administration of 125 mg of OPZ led to a 2.6-fold increase in excretion of aflatoxin-mercapturic acid without any effect on AFMl level in contrast, weekly administration of 500 mg over one month led to a 51% decrease of AFMl in urine without any effect on aflatoxinmercapturic acid excretion. The decreased AFMl excretion can be interpreted as an inhibition of CYP1A2 activity and the increase of AFBl-mercapturic acid as an increased conjugation of AFBl-8,9-epoxides with GSH. 

The observation that naphthalene feeding produced cataracts in rabbits suggested a relationship between mercapturic acid formation and sulfur amino acid metabolism in mammals, In the period between World Wars I and II, most advances in the biochemistrj of mei capturic acids were made through study of tlie nutritional effects produced by mercapturic acid precursors. During this period, the concept of mercapturic acids as... 

The toxic effects of hydrocarbons are well established. Injection of 150 mg/kg of bromobenzene into rats produces acute centrolobulm- hepatic necrosis within 48 hours (Koch-Weser el al., 1952). The toxieitj is related to the general nutiitional state, ilethionine and cj stine, or a high protein diet, effectively combat the effects of the hydrocarbons. Koch-Weser suggests the liver damage is due to removal of cysteine and methionine, since p-dibromobenzene and p-bromochlorobenzene, which do not form mercapturic acids, do not cause hepatic lesions while w-chloro-... 

It is possible that the growth inhibition produced by hydrocarbons results from depletion of glutathione in liver. The tripeptide is a vital catalyst in the s3mthesis of protein. Loiier term growth inhibitions produced by hydrocarbons which form insignificant amounts of mercapturic acids presumably result from other effects. 

It is of interest that Grover and Sims (1964) found that aromatic hydrocarbons and narcotics, which induce hydroxylase activity, have a depressant effect on glutathione iS-arjdtransferase. Hydroxylases have a practically unlimited supply of substrate while the conjugases require glutathione, which rapidly depletes the liver. Nevertheless a severe sulfur amino acid defidency be generated by administration of bromo-benzene and other hydrocarbons or derivatives w-hich are metabolized to proportionately large amounts of mercapturic acids. 

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