Combined quercetin and simvastatin attenuate hepatic fibrosis in rats by modulating SphK1/NLRP3 pathways.

Autor: Salama YA; Department of Biochemistry, Faculty of Pharmacy, Mansoura University, 35516, Egypt; Department of Pharmacology and Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 11152, Egypt., Hassan HM; Department of Pharmacology and Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 11152, Egypt., El-Gayar AM; Department of Biochemistry, Faculty of Pharmacy, Mansoura University, 35516, Egypt., Abdel-Rahman N; Department of Biochemistry, Faculty of Pharmacy, Mansoura University, 35516, Egypt. Electronic address: noha82@mans.edu.eg.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2024 Jan 15; Vol. 337, pp. 122349. Date of Electronic Publication: 2023 Dec 19.
DOI: 10.1016/j.lfs.2023.122349
Abstrakt: Liver fibrosis involves several signalling pathways working in concert regulating the deposition of extracellular matrix. In this study, we evaluated the effect of quercetin and simvastatin alone and their combination on the treatment of experimentally induced hepatic fibrosis in rats. To decipher the potential mechanisms involved, liver fibrosis was induced in rats by administration of 40 % carbon tetrachloride (CCl 4 ) (1 μl/g rat, i.p., twice weekly) for 6 weeks. Quercetin (50 mg/kg, orally), simvastatin (40 mg/kg, orally) either individually or combined were administered for another 4 weeks. The three treatment groups ameliorated hepatic dysfunction and altered parameters of sphingolipid and pyroptosis pathways. Yet, the combined group showed a more pronounced effect. Treatments lowered serum levels of GOT, GPT, ALP and elevated albumin and total protein levels. Histopathological and electron microscope examination of liver tissue revealed diminished fibrosis and inflammation. Protein expression levels of α-SMA, IL-1β, PPAR-γ, TGF-β1, caspase-1 and caspase-3 expression in liver tissues were reduced. Additionally, hepatic mRNA levels of SphK1 and NLRP3 decreased after treatment. Furthermore, the three groups lowered MDA levels and elevated total antioxidant capacity, GSH and Nrf2 expression levels. Treatments downregulated sphingolipid pathway and NLRP3-mediated pyroptosis and stimulated an anti-apoptotic, anti-proliferative and antioxidant activity. This suggests that targeting the SphK1/NLRP3 pathway could be a prospective therapeutic strategy against liver fibrosis.
Competing Interests: Declaration of competing interest Authors state that this experiment was performed in absence of any competing financial, personal, or commercial interests that could exert influence on reported data in this study.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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