Antidotal effect of sodium thiosulfate in mice exposed to acrylonitrile.
Although acute acrylonitrile (ACN) toxicity is very profound, the mechanism of its toxicity and immediate lethality is unclear. Many have suggested that ACN or its reactive metabolite acts directly at the target tissues, while others have implicated the release of CN ions from the parent compound as the toxic moiety. Since sodium thiosulfate (STS) is both an effective cyanide antidote and neutralizing agent capable of binding to reactive chemicals or metabolites, its antidotal role was investigated in mice exposed to 60 mg/kg intraperitoneal (IP) ACN injection. Treatment with an IP injection of 400 mg/kg of STS from 10 to 30 minutes before ACN administration protected animals from ACN-induced lethality. All mice appeared normal after prophylactic treatment with STS and showed no ill effects from ACN exposure. Similar data was observed when STS was administered 10 and 30 minutes after ACN administration. Non-protein sulfhydryl (NPSH) concentration was determined in the brain, kidneys, and liver of the mice exposed to a single or multiple doses of STS and ACN. The levels of NPSH were significantly lowered by ACN in the liver (45% of the control), and kidneys (51% of the control), whereas in the brain NPSH levels were least affected and decreased modestly (85% of the control) following either acute or chronic administration of acrylonitrile. The data indicate a marked protective effect of STS either before or after ACN exposure and this STS-induced antidotal response does not involve GSH in the brain.
Mehta
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Minority Center for Toxicology Research, College of Pharmacy and Health Sciences, Texas Southern University, Houston 77004, USA.
D000181:Acrylonitrile / Q000633:toxicity*; D000818:Animals; D000931:Antidotes / Q000008:administration & dosage / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D013885:Thiosulfates / Q000008:administration & dosage / Q000494:pharmacology*
D000931:Antidotes; D013885:Thiosulfates; D005978:Glutathione; C017717:sodium thiosulfate; D000181:Acrylonitrile