Your browser doesn't support javascript.
loading
Identification of an Epoxide Metabolite of Amitriptyline In Vitro and In Vivo.
Li, Ximei; Xin, Lihua; Yang, Lan; Yang, Yi; Li, Wei; Zhang, Mingyu; Liao, Yufen; Sun, Chen; Li, Weiwei; Peng, Ying; Zheng, Jiang.
Afiliação
  • Li X; State Key Laboratory of Functions and Applications of Medicinal Plants, Key Laboratory of Pharmaceutics of Guizhou Province, Guizhou Medical University, Guiyang, Guizhou 550025, P. R. China.
  • Xin L; Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, P. R. China.
  • Yang L; Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, P. R. China.
  • Yang Y; Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, P. R. China.
  • Li W; Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, P. R. China.
  • Zhang M; Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, P. R. China.
  • Liao Y; State Key Laboratory of Functions and Applications of Medicinal Plants, Key Laboratory of Pharmaceutics of Guizhou Province, Guizhou Medical University, Guiyang, Guizhou 550025, P. R. China.
  • Sun C; Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, P. R. China.
  • Li W; State Key Laboratory of Functions and Applications of Medicinal Plants, Key Laboratory of Pharmaceutics of Guizhou Province, Guizhou Medical University, Guiyang, Guizhou 550025, P. R. China.
  • Peng Y; Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, P. R. China.
  • Zheng J; State Key Laboratory of Functions and Applications of Medicinal Plants, Key Laboratory of Pharmaceutics of Guizhou Province, Guizhou Medical University, Guiyang, Guizhou 550025, P. R. China.
Chem Res Toxicol ; 37(6): 935-943, 2024 Jun 17.
Article em En | MEDLINE | ID: mdl-38761382
ABSTRACT
Amitriptyline (ATL), a tricyclic antidepressant, has been reported to cause various adverse effects, particularly hepatotoxicity. The mechanisms of ATL-induced hepatotoxicity remain unknown. The study was performed to identify the olefin epoxidation metabolite of ATL and determine the possible toxicity mechanism. Two glutathione (GSH) conjugates (M1 and M2) and two N-acetylcysteine (NAC) conjugates (M3 and M4) were detected in rat liver microsomal incubations supplemented with GSH and NAC, respectively. Moreover, M1/M2 and M3/M4 were respectively found in ATL-treated rat primary hepatocytes and in bile and urine of rats given ATL. Recombinant P450 enzyme incubations demonstrated that CYP3A4 was the primary enzyme involved in the olefin epoxidation of ATL. Treatment of hepatocytes with ATL resulted in significant cell death. Inhibition of CYP3A attenuated the susceptibility to the observed cytotoxicity of ATL. The metabolic activation of ATL most likely participates in the cytotoxicity of ATL.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Microssomos Hepáticos / Ratos Sprague-Dawley / Hepatócitos / Compostos de Epóxi / Citocromo P-450 CYP3A / Amitriptilina Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Microssomos Hepáticos / Ratos Sprague-Dawley / Hepatócitos / Compostos de Epóxi / Citocromo P-450 CYP3A / Amitriptilina Idioma: En Ano de publicação: 2024 Tipo de documento: Article