Revealing how phenytoin triggers liver damage and the potential protective effects of Balanites Aegyptiaca fruit extracts: Exploring Nrf2/MAPK/ Beclin-1 signaling pathways.
Rats
Male
Animals
Phenytoin
/ metabolism
Plant Extracts
/ chemistry
NF-E2-Related Factor 2
/ metabolism
Balanites
/ chemistry
Beclin-1
/ metabolism
NF-kappa B
/ metabolism
Fruit
Molecular Docking Simulation
Oxidative Stress
Liver
MAP Kinase Signaling System
Chemical and Drug Induced Liver Injury
/ etiology
Anti-inflammatory
Antioxidant
Balanites Aegyptiaca
Butanol extract
Ethyl acetate extract
Liver function
Nrf2/MAPK signals
Phenytoin
Phenytoin Idiosyncratic Induced Liver Injury
Journal
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
ISSN: 1950-6007
Titre abrégé: Biomed Pharmacother
Pays: France
ID NLM: 8213295
Informations de publication
Date de publication:
Sep 2023
Sep 2023
Historique:
received:
31
05
2023
revised:
24
07
2023
accepted:
31
07
2023
medline:
17
8
2023
pubmed:
5
8
2023
entrez:
4
8
2023
Statut:
ppublish
Résumé
Phenytoin-induced liver injury (PHT ILII) is a serious condition that may necessitate discontinuation of the drug. This study investigates the mechanisms of PHT ILII and evaluates the protective effects of Balanites Aegyptiaca (BA) fruit extracts on the liver. We focus on the Nrf2/MAPK/NF-κB/Beclin-1 signaling pathways involved in oxidative stress and inflammation from drug-induced liver injury. Phytochemical analyses of BA fruit extracts (Bu-F and EA-F) are conducted. Molecular docking techniques explore the interaction between phenytoin (PHT) and the Nrf2/MAPK/NF-κB/Beclin-1 pathways. Thirty-six male rats are divided into Control, Bu-F, EA-F, PHT, Bu-F/PHT, and EA-F/PHT groups, and they are observed for 45 days. EA-F extract is rich in phenolics/flavonoids, while Bu-F extract mainly contains saponins.PHT ILII causes histological damage in liver tissues and affects Nrf-2, MAPK, TNF-α, IL-1β, Mcp-1, Beclin-1, iNOS expression, and liver function markers (ALT, AST, ALP). However, EA-F/Bu-F extracts effectively improve the histological structure and significantly reduce biochemical/immunohistochemical parameters, restoring them to near-normal levels. EA-F extract is particularly effective.In conclusion, the Nrf2/MAPK /Beclin-1 pathways play a critical role in the development of PHT ILII. BA fruit extracts show promise as hepato-protective agents, with the EA-F extract demonstrating superior efficacy. These results lay the groundwork for new treatments for PHT ILII and drug-induced liver injuries.
Identifiants
pubmed: 37541174
pii: S0753-3322(23)01056-9
doi: 10.1016/j.biopha.2023.115265
pii:
doi:
Substances chimiques
Phenytoin
6158TKW0C5
Plant Extracts
0
NF-E2-Related Factor 2
0
Beclin-1
0
NF-kappa B
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
115265Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest It is stated by the authors that they have no competing interests. The funding, the content, and the drafting of this paper are all the exclusive responsibility of the authors.