Relationship of tissue nonprotein/sulfhydryls to the acute toxic effects of 1,2-dibromo-3-chloropropane.
Subcutaneous administration of the nematocide, 1,2-dibromo-3-chloropropane (DBCP), to adult, male, Fischer 344 rats transiently depleted hepatic and caput (head) epididymal nonprotein sulfhydryl (NPS) contents. NPS concentrations in the testis and kidney were not lowered by DBCP. Liver, kidney and testis all exhibited increases in tissue NPS concentrations 48 hr after treatment; the effects were most prominent in the outer medullary section of the kidney 24 hr after treatment with 80 mg/kg of DBCP. The glutathione-depleting agent diethyl maleate transiently lowered hepatic, renal and caput epididymal NPS concentrations in a dose- and time-dependent manner. Renal and caput epididymal NPS contents were increased relative to control 24 hr after diethyl maleate treatment. Single s.c. injections of DBCP produced dose-dependent lesions in the kidney, testis, caput epididymis and liver. Diethyl maleate treatment 90 min before DBCP treatment enhanced the nephrotoxic potency of DBCP as indicated by greater elevations of blood urea nitrogen and serum creatinine concentrations and by more severe renal tubular necrosis in diethyl maleate-pretreated animals than in vehicle controls, as determined 48 hr after DBCP exposure. Seminiferous tubular degeneration, as determined 48 hr post-DBCP treatment, was greater in rats pretreated with 600 mg/kg of diethyl maleate than in nonpretreated controls. When examined 16 days after DBCP treatment, however, the severity of testicular atrophy was virtually the same in rats pretreated with a lower dose of diethyl maleate (400 mg/kg) as in nonpretreated rats. These results indicate that DBCP is a depletor of hepatic and caput epididymal NPS in the acutely toxic dose range. Inasmuch as NPS concentrations were not lowered in two of the major target organs, kidney and testis, acute DBCP injury would not appear to be dependent on local glutathione depletion. However, the greater susceptibility of kidney and testis to DBCP injury after diethyl maleate pretreatment suggests an important role for NPS, particularly those in the liver, in modulating DBCP toxicities.
D000818:Animals; D000969:Antinematodal Agents / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006846:Hydrocarbons, Halogenated / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008298:Maleates / Q000494:pharmacology; D011407:Propane / Q000031:analogs & derivatives* / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D013737:Testis / Q000187:drug effects / Q000378:metabolism
D000969:Antinematodal Agents; D006846:Hydrocarbons, Halogenated; D008298:Maleates; D013438:Sulfhydryl Compounds; C007318:1,2-dibromo-3-chloropropane; C014476:diethyl maleate; D011407:Propane