Thymol Protects against 5-Fluorouracil-Induced Hepatotoxicity via the Regulation of the Akt/GSK-3β Pathway in In Vivo and In Silico Experimental Models.

Autor: Mahran YF; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt., Badr AM; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11211, Saudi Arabia., Al-Kharashi LA; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11211, Saudi Arabia., Alajami HN; College of Pharmacy, King Saud University, Riyadh 11211, Saudi Arabia., Aldamry NT; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11211, Saudi Arabia., Bayoumy NM; Department of Physiology, College of Medicine, King Saud University, Riyadh 11211, Saudi Arabia., Elmongy EI; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Ain Helwan, Cairo 11795, Egypt., Soliman S; Department of Physiology and Pharmacology, College of Osteopathic Medicine, Sam Houston State University, Conroe, TX 77304, USA.
Jazyk: angličtina
Zdroj: Pharmaceuticals (Basel, Switzerland) [Pharmaceuticals (Basel)] 2024 Aug 21; Vol. 17 (8). Date of Electronic Publication: 2024 Aug 21.
DOI: 10.3390/ph17081094
Abstrakt: Background: 5-fluorouracil (5-FU) is a widely used, highly effective chemotherapeutic agent. However, its therapeutic efficacy is often limited by associated adverse effects, with hepatotoxicity being frequently reported with 5-FU therapy. Thymol is a monoterpene found in thyme ( Thymus vulgaris L., Lamiaceae) and is known for its antioxidant, anti-apoptotic, and anticancer activities. This study aimed to explore the hepatoprotective activity of thymol against 5-FU-induced liver injury.
Methods: Rats received two intraperitoneal doses of 5-FU (150 mg/kg) either alone or in combination with thymol at doses of 60 mg/kg or 120 mg/kg. Liver enzymes, oxidative stress, and apoptotic markers, in addition to histopathological changes, were assessed.
Results: 5-FU induced marked liver injuries as evidenced by elevated liver enzymes and histopathological changes, in addition to abnormalities of oxidative and apoptotic markers. The administration of thymol ameliorated the 5-FU-induced oxidative damage through increasing hepatic antioxidants and lowering lipid peroxidation. Apoptotic response markers such as Bax, Bcl-2, Bax/Bcl-2 ratio, and PARP were also improved. Furthermore, Western blotting analysis showed that thymol modulated the 5-FU-induced changes in the expression of Akt/GSK-3β and p44/42 MAPK (ERK1/2) signaling pathways.
Conclusions: Our research is the first to shed light on thymol's potential protective effect against 5-FU- induced hepatotoxicity by inhibiting oxidative and apoptotic pathways and modulating the Akt/ GSK-3β as well as p44/42 MAPK (ERK1/2) signaling pathways.
Databáze: MEDLINE
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