Type 2 diabetes mellitus potentiates acute acrylonitrile toxicity: Potentiation reduction by phenethyl isothiocyanate.
Toxicol Ind Health
; 37(11): 695-704, 2021 Nov.
Article
em En
| MEDLINE
| ID: mdl-34643460
ABSTRACT
Acrylonitrile (AN) is a known animal carcinogen and suspected human carcinogen. Recently, occupational exposure to AN has considerably increased. Previously, we demonstrated that streptozotocin-induced diabetes potentiates AN-induced acute toxicity in rats and that the induced cytochrome P450 2E1 (CYP2E1) is responsible for this effect. In the present study, we examined whether induction of CYP2E1 is also the underlying mechanism for the potentiation of AN-induced acute toxicity in type 2 diabetes in db/db mice. The effect of phenethyl isothiocyanate (PEITC) in reducing potentiation was also investigated. The mice were randomly divided into the normal control, diabetic control, AN, diabetes + AN, PEITC + AN, and diabetes + PEITC + AN groups. PEITC (40 mg/kg) was orally administered to rats for 3 days, and 1 h after the last PEITC gavage, 45 mg/kg AN was intraperitoneally injected. Time to death was observed. The CYP2E1 level and enzymatic activity, cytochrome c oxidase (CCO) activity, and reactive oxygen species (ROS) levels were measured. The survival rate was decreased in AN-treated db/db mice compared with that in AN-treated wild-type mice. The hepatic CYP2E1 level and enzymatic activity remained unaltered in db/db mice. Phenethyl isothiocyanate alleviated AN-induced acute toxicity in db/db mice as evident in the increased survival rate, restored CCO activity, and decreased ROS level in both the liver and brain. The study results suggested that CYP2E1 may not be responsible for the sensitivity to AN-induced acute toxicity in db/db mice and that PEITC reduced the potentiation of AN-induced acute toxicity in db/db mice.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
1_ASSA2030
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6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Acrilonitrila
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Diabetes Mellitus Tipo 2
Limite:
Animals
Idioma:
En
Revista:
Toxicol Ind Health
Ano de publicação:
2021
Tipo de documento:
Article