Neuroprotective effect of diosmin against chlorpyrifos-induced brain intoxication was mediated by regulating PPAR-γ and NF-κB/AP-1 signals.

Autor: Abd-Elhamid TH; Department of Histology and Cell Biology, Faculty of Medicine, Assiut University, Assiut, 71515, Egypt; Department of Basic Medical Sciences, Faculty of Medicine, Aqaba Medical Sciences University, Aqaba, 77110, Jordan., Althumairy D; Department of Biological Sciences, Faculty of Science, King Faisal University, Al-Ahsa, 31982, Saudi Arabia., Bani Ismail M; Department of Basic Medical Sciences, Faculty of Medicine, Aqaba Medical Sciences University, Aqaba, 77110, Jordan., Abu Zahra H; Department of Biological Sciences, Faculty of Science, King Faisal University, Al-Ahsa, 31982, Saudi Arabia., Seleem HS; Histology Department, Faculty of Medicine, Menoufia University, Shebin ElKoum-Menoufia, Egypt; Department of Basic Medical Sciences, Unaizah College of Medicine and Medical Sciences, Qassim University, Kingdom of Saudi Arabia., Hassanein EHM; Department of Pharmacology & Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut, 71524, Egypt., Ali FEM; Department of Pharmacology & Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut, 71524, Egypt; Michael Sayegh, Faculty of Pharmacy, Aqaba University of Technology, Aqaba, 77110, Jordan. Electronic address: Faresali@azhar.edu.eg., Mahmoud AR; Department of Human Anatomy and Embryology, Faculty of Medicine, Assiut University, Assiut, 71515, Egypt; Department of Anatomy and Histology, College of Medicine, Qassim University, Kingdom of Saudi Arabia.
Jazyk: angličtina
Zdroj: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association [Food Chem Toxicol] 2024 Nov; Vol. 193, pp. 114967. Date of Electronic Publication: 2024 Aug 27.
DOI: 10.1016/j.fct.2024.114967
Abstrakt: Chlorpyrifos (CPF) is a widely used organophosphate (OP) pesticide. Unfortunately, pesticides are known to cause neuronal intoxication. Diosmin (DS) is an antioxidant, anti-inflammatory, and neuroprotective flavonoid with high efficacy and safety. We plan to investigate the efficacy of DS in treating CPF-induced neurotoxicity, as well as the mechanisms underlying the protective effects. In our study, rats were randomized into 5 groups: control, DS (50 mg/kg), CPF (10 mg/kg), CPF + DS (25 mg/kg), and CPF + DS (50 mg/kg). The results indicated that DS ameliorated neuronal intoxication induced by CPF, evidenced by decreasing Tau, p-Tau, and β-amyloid. Histological examinations support these findings. DS significantly ameliorated CPF-induced neuronal oxidative injury by decreasing MDA content and elevating GSH, GST, and SOD levels mediated by PPAR-γ upregulation. DS suppressed CPF-induced brain inflammation by decreasing MPO enzymatic activity and TNF-α, IL-1β, and IL-6 levels mediated by downregulation of NF-κB/AP-1(c-FOS and c-JUN) signal. Of note, DS protective effects were dose dependent. In conclusion, our data suggested that DS was a promising therapeutic strategy for attenuating CPF-induced neuronal intoxication by restoring oxidant-antioxidant balance and inhibiting inflammatory response in brain tissues.
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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