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Biotransformation of carbamazepine and nicotine in juvenile American alligator (Alligator mississippiensis) in vitro hepatic S9 vs. in situ perfused liver.

Authors :
Umeki Y
Hala D
Petersen LH
Source :
Comparative biochemistry and physiology. Toxicology & pharmacology : CBP [Comp Biochem Physiol C Toxicol Pharmacol] 2024 Sep 03; Vol. 287, pp. 110015. Date of Electronic Publication: 2024 Sep 03.
Publication Year :
2024
Publisher :
Ahead of Print

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 (CL <subscript>f,int</subscript> ) 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' CL <subscript>f,int</subscript> 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.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1532-0456
Volume :
287
Database :
MEDLINE
Journal :
Comparative biochemistry and physiology. Toxicology & pharmacology : CBP
Publication Type :
Academic Journal
Accession number :
39237053
Full Text :
https://doi.org/10.1016/j.cbpc.2024.110015