Prevention of fenitrothion induced hepatic toxicity by saponarin via modulating TLR4/MYD88, JAK1/STAT3 and NF-κB signaling pathways.

Autor: Hassan HM; Department of pathology, College of Medicine, King Khalid University, Abha, Saudi Arabia., El Safadi M; Department of Chemistry, College of Science, United Arab Emirates University, P.O. Box 15551, Al Ain, Abu Dhabi , United Arab Emirates., Hayat MF; Department of Zoology, Wildlife and Fisheries, University of Agriculture, Faisalabad, Pakistan. Electronic address: 2019ag3319@uaf.edu.pk., Al-Emam A; Department of Pathology, College of Medicine, King Khalid University, Asir 61421, Saudi Arabia; Department of Forensic Medicine and Clinical Toxicology, Mansoura University, Egypt.
Jazyk: angličtina
Zdroj: The international journal of biochemistry & cell biology [Int J Biochem Cell Biol] 2024 Dec 05; Vol. 179, pp. 106716. Date of Electronic Publication: 2024 Dec 05.
DOI: 10.1016/j.biocel.2024.106716
Abstrakt: Fenitrothion (FEN) is an organophosphate insecticidal agent that is considered as major source of organs toxicity. Saponarin (SAP) is a naturally occurring novel flavone that exhibits a wide range of medicinal properties. The current trial was conducted to evaluate the ameliorative potential of SAP against FEN instigated liver toxicity in rats. Thirty-two male albino rats were apportioned into four groups including control, FEN (10 mg/kg), FEN (10 mg/kg) + SAP (80 mg/kg), and SAP (80 mg/kg) alone treated group. It was revealed that FEN administration upregulated the gene expression of TNF-α, TLR4, IL-1β, MYD88, IL-6, TRAF6, COX-2, NF-κB, JAK1 and STAT3 while reducing the gene expression of IκB. Moreover, the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) were increased while the activities of catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), heme-oxygenase-1 (HO-1) and glutathione reductase (GSR) were decreased after FEN exposure. Furthermore, FEN administration notably escalated the levels of hepatic enzymes including alanine transaminase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) whereas reduced the levels of total proteins and albumin. Besides, FEN intake upregulated the levels of Caspase-9, Bax and Caspase-3 while reducing the levels of Bcl-2. Hepatic histology was impaired after FEN intoxication. Nonetheless, SAP treatment remarkably protected the normal state of liver via regulating abovementioned irregularities. Our in-silico analysis confirmed that SAP hold that potential to interact with binding pocket of these proteins, highlighting its ability as a therapeutic compound to alleviate FEN-induced liver damage.
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.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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