Gender-related difference in the toxicity of 2-(2′-hydroxy-3′,5′-di-tert-butylphenyl)benzotriazole in rats: Relationship to the plasma concentration,in vitrohepatic metabolism, and effects on hepatic metabolizing enzyme activity
| Autor: | Takashi Matsuyama, Mutsuko Hirata-Koizumi, Akihiko Hirose, Mitsuhiko Kawabata, Kiyomi Matsuno, Eiichi Kamata, Kanako Yajima, Makoto Ema |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Male
Ribosomal Proteins medicine.medical_specialty Health Toxicology and Mutagenesis Administration Oral In Vitro Techniques Toxicology Rats Sprague-Dawley chemistry.chemical_compound Sex Factors Tandem Mass Spectrometry Internal medicine Toxicity Tests Blood plasma medicine Animals Incubation Chromatography High Pressure Liquid NADPH-Ferrihemoprotein Reductase Pharmacology Chemical Health and Safety Benzotriazole biology Ribosomal Protein S9 Body Weight Public Health Environmental and Occupational Health General Medicine Metabolism Triazoles In vitro Enzyme assay Rats Endocrinology Liver chemistry Toxicity Microsomes Liver biology.protein Female Drug metabolism |
| Zdroj: | Drug and Chemical Toxicology. 32:204-214 |
| ISSN: | 1525-6014 0148-0545 |
| Popis: | Previously, we showed that the toxic susceptibility of male rats to an ultraviolet absorber, 2-(2'-hydroxy- 3',5'-di-tert-butylphenyl)benzotriazole (HDBB), was nearly 25 times higher than that of females. The present study aimed to clarify the mechanism of gender-related differences in HDBB toxicity. Male and female rats were given HDBB by gavage at 0.5, 2.5, or 12.5 mg/kg/day for 28 days, and plasma HDBB levels were measured at various time points by using liquid chromatography-tandem mass spectrometry. HDBB was rapidly absorbed and eliminated from the plasma in both sexes, and no sexual variations were found in the plasma levels. In the plasma, HDBB metabolites were not detected at any dose by the liquid chromatography-photodiode array detector. In an in vitro metabolic study using hepatic microsomes from male and female rats, HDBB was slightly metabolized, but no sexual differences were found in the residual HDBB ratio after a 60-minute incubation with an NADPH-generation system. Following 28-day HDBB administration, sexually different changes were found in cytochrome P450-dependent microsomal mixed-function oxidase activities in the liver. In males, 7-ethoxyresorufin O-deethylase activity decreased and lauric acid 12-hydroxylase activity increased at all doses. Decreases in aminopyrine N-demethylase activity and testosterone 2alpha- and 16alpha-hydroxylase activity were also found at 2.5 mg/kg and above in males. In females, the only significant change was increased lauric acid 12-hydroxylase activity at 12.5 mg/kg. These findings indicate that HDBB would have hepatic peroxisome proliferative activity, and the difference in susceptibility of male and female rats to this effect might lead to marked gender-related differences in HDBB toxicity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
| Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |