Investigating the tamoxifen/high-fat diet synergy: a promising paradigm for nonalcoholic steatohepatitis induction in a rat model.

Autor: Ezz-Eldin YM; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Nahda University, Beni-Suef, Egypt. Yusra.mahmoud@nub.edu.eg.; Department of Pharmacology & Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt. Yusra.mahmoud@nub.edu.eg., Ewees MG; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Nahda University, Beni-Suef, Egypt., Azouz AA; Department of Pharmacology & Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt., Khalaf MM; Department of Pharmacology & Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt. Marwa.khalaf@pharm.bsu.edu.eg.
Jazyk: angličtina
Zdroj: Naunyn-Schmiedeberg's archives of pharmacology [Naunyn Schmiedebergs Arch Pharmacol] 2024 Nov; Vol. 397 (11), pp. 9067-9079. Date of Electronic Publication: 2024 Jun 17.
DOI: 10.1007/s00210-024-03192-7
Abstrakt: Non-alcoholic steatohepatitis (NASH) is a severe liver condition characterized by excessive fat deposition, ballooning, and lobular inflammation. This investigation was conducted to estimate the capability of concomitant tamoxifen administration (TAM) with a high fat diet (HFD) to induce a reliable NASH model that mimics human NASH features. Rats were administered TAM (25 mg/kg/day p.o.) and consumed HFD for 5 weeks. A time-course investigation was conducted to determine the optimal time for NASH development. Liver function indices, hepatic lipid profile factors, oxidative stress biomarkers, and inflammatory mediators were estimated. Additionally, macroscopic and microscopic changes were examined. Compared with the time-matched control group receiving vehicle alone, TAM/HFD significantly impaired liver function indices represented as marked elevation in ALT, AST, and ALP serum levels. TAM/HFD significantly increased lipid profile factors including high TG and TC hepatic levels. Additionally, TAM/HFD remarkably raised hepatic levels of TNF-α and IL-17 and significantly decreased IL-10. The combination also increases the oxidative status evidenced by high content of MDA as well as low activity of GPx and SOD. Accordingly, the combination of TAM and HFD for 5 weeks collaboratively promotes NASH development by initiating compromised hepatocyte functionality, elevated lipid levels, oxidative stress, and liver inflammation.
(© 2024. The Author(s).)
Databáze: MEDLINE
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