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Biotransformation of carbamazepine and nicotine in juvenile American alligator (Alligator mississippiensis) in vitro hepatic S9 vs. in situ perfused liver.
Umeki, Yu; Hala, David; Petersen, Lene H.
Afiliação
  • Umeki Y; Department of Marine Biology, Texas A&M University at Galveston, Galveston, TX 77553, USA. Electronic address: yumeki.tamug@gmail.com.
  • Hala D; Department of Marine Biology, Texas A&M University at Galveston, Galveston, TX 77553, USA.
  • Petersen LH; Department of Marine Biology, Texas A&M University at Galveston, Galveston, TX 77553, USA.
Comp Biochem Physiol C Toxicol Pharmacol ; 287: 110015, 2024 Sep 03.
Article em En | MEDLINE | ID: mdl-39237053
ABSTRACT
American alligators (Alligator mississippiensis) are apex predators and sentinel species in the coastal wetland ecosystem along the Gulf of Mexico. There is concern for alligator exposure and susceptibility to chemical contaminants due to their high trophic level and lower metabolic capability. At present, their hepatic biotransformation capacity to metabolize or detoxify contaminants has not been comprehensively determined. In this study, the hepatic biotransformation capability of juvenile American alligators to metabolize two commonly found environmental pharmaceuticals carbamazepine (CBZ) or nicotine (NCT) was evaluated. The formation of their respective primary metabolites, i.e., carbamazepine-10,11-epoxide (CBZ-E) and cotinine (CTN), was evaluated at 10 µM (within the human therapeutic range). The in vitro S9 and a novel in situ liver perfusion assays were used to characterize and compare metabolic ability in isolated hepatic enzymes vs. whole organ (liver). For CBZ, the perfused livers exhibited only 30% of intrinsic formation clearance (CLf,int) relative to the S9 assay. The metabolism of NCT was not detectable in the S9 assay and was only observed in the perfused liver assay. Compared to the corresponding rat models (S9 or perfused livers),alligators' CLf,int was 2060% for CBZ and 50% for NCT of rats. Additionally, NCT exposure increased lactate levels in perfused livers indicating metabolic stress. This study provides insight into the hepatic capability of alligators to metabolize CBZ and NCT using an established in vitro (S9) system and a newly developed in situ liver perfusion system.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Comp Biochem Physiol C Toxicol Pharmacol Assunto da revista: FARMACOLOGIA / TOXICOLOGIA Ano de publicação: 2024 Tipo de documento: Article País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Comp Biochem Physiol C Toxicol Pharmacol Assunto da revista: FARMACOLOGIA / TOXICOLOGIA Ano de publicação: 2024 Tipo de documento: Article País de publicação: Estados Unidos