Role of Platelet-activating factor and HO-1 in mediating the protective effect of rupatadine against 5-fluorouracil-induced hepatotoxicity in rats.

Autor: Khalaf HM; Department of Pharmacology, Faculty of Medicine, Minia University, Minia, Egypt., Hafez SMNA; Department of Histology and Cell Biology, Faculty of Medicine, Minia University, Minia, Egypt., Abdalla AM; Department of Biochemistry, Faculty of Medicine, Minia University, Minia, Egypt., Welson NN; Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt. nermeennemr@yahoo.com., Abdelzaher WY; Department of Pharmacology, Faculty of Medicine, Minia University, Minia, Egypt., Abdelbaky FAF; Department of Anatomy, Faculty of Medicine, Minia University, Minia, Egypt.
Jazyk: angličtina
Zdroj: Environmental science and pollution research international [Environ Sci Pollut Res Int] 2022 Jun; Vol. 29 (26), pp. 40190-40203. Date of Electronic Publication: 2022 Feb 04.
DOI: 10.1007/s11356-022-18899-4
Abstrakt: 5-fluorouracil (5-FU) is a widely used chemotherapeutic drug, but its hepatotoxicity challenges its clinical use. Thus, searching for a hepatoprotective agent is highly required to prevent the accompanied hepatic hazards. The current study aimed to investigate the potential benefit and mechanisms of action of rupatadine (RU), a Platelet-activating factor (PAF) antagonist, in the prevention of 5-FU-related hepatotoxicity in rats. Hepatotoxicity was developed in male albino rats by a single 5-FU (150 mg/kg) intra-peritoneal injection on the 7th day of the experiment. RU (3 mg/kg/day) was orally administrated to the rodents for 10 days. Hepatic toxicity was assessed by measuring both liver and body weights, serum alanine aminotransferase and aspartate aminotransferase (ALT and AST), hepatic oxidative stress parameters (malondialdehyde (MDA), nitric oxide levels (NOx), reduced glutathione (GSH), superoxide dismutase (SOD)), and heme oxygenase-1 (HO-1). Inflammatory markers expressions (inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNFα), interleukins; IL-1B, IL-6), the apoptotic marker (caspase-3), and PAF were measured in the hepatic tissue. 5-FU-induced hepatotoxicity was proved by the biochemical along with histopathological assessments. RU ameliorated 5-FU-induced liver damage as proved by the improved serum ALT, AST, and hepatic oxidative stress parameters, the attenuated expression of hepatic pro-inflammatory cytokines and PAF, and the up-regulation of HO-1. Therefore, it can be concluded that RU pretreatment exerted a hepatoprotective effect against 5-FU-induced liver damage through both its powerful anti-inflammatory, antioxidant, and anti-apoptotic effect.
(© 2022. The Author(s).)
Databáze: MEDLINE
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