The potential protective effect of liraglutide on valproic acid induced liver injury in rats: Targeting HMGB1/RAGE axis and RIPK3/MLKL mediated necroptosis.

Autor: Atef MM; Department of Medical Biochemistry, Faculty of Medicine, Tanta University, Tanta, Egypt., Abou Hashish NA; Department of Pharmacology, Faculty of Medicine, Tanta University, Tanta, Egypt., Hafez YM; Department of Internal Medicine, Faculty of Medicine, Tanta University, Tanta, Egypt., Selim AF; Department of Internal Medicine, Faculty of Medicine, Tanta University, Tanta, Egypt., Ibrahim HA; Department of Medical Biochemistry, Faculty of Medicine, Tanta University, Tanta, Egypt., Eltabaa EF; Department of Medical Physiology, Faculty of Medicine, Tanta University, Tanta, Egypt., Rizk FH; Department of Medical Physiology, Faculty of Medicine, Tanta University, Tanta, Egypt., Shalaby AM; Department of Histology, Faculty of Medicine, Tanta University, Tanta, Egypt., Ezzat N; Department of Toxicology, Faculty of Medicine, Tanta University, Tanta, Egypt., Alabiad MA; Department of Pathology, Faculty of Medicine, Zagazig University, Tanta, Egypt., Elshamy AM; Department of Medical Biochemistry, Faculty of Medicine, Tanta University, Tanta, Egypt.
Jazyk: angličtina
Zdroj: Cell biochemistry and function [Cell Biochem Funct] 2023 Dec; Vol. 41 (8), pp. 1209-1219. Date of Electronic Publication: 2023 Sep 28.
DOI: 10.1002/cbf.3855
Abstrakt: Valproic acid (VPA) is a commonly used drug for management of epilepsy. Prolonged VPA administration increases the risk of hepatotoxicity. Liraglutide is a glucagon-like peptide 1 receptor (GLP-1R) agonist that act as a novel antidiabetic drug with broad-spectrum anti-inflammatory and antioxidant effects. This study tested the protective effect of liraglutide against VPA-induced hepatotoxicity elucidating the possible underlying molecular mechanisms. Forty adult male rats were allocated in to four equally sized groups; Group I (control group) received oral distilled water and subcutaneous normal saline for 2 weeks followed by subcutaneous normal saline only for 2 weeks. Group II (liraglutide group) received subcutaneous liraglutide dissolved in normal saline daily for 4 weeks. Group III (valproic acid-treated group) received sodium valproate dissolved in distilled water for 2 weeks. Group IV (Combined valproic acid & liraglutide treated group) received valproic acid plus liraglutide daily for 2 weeks which was continued for additional 2 weeks after valproic acid administration. The hepatic index was calculated. Serum AST, ALT, GGT, and ALP activities were estimated. Hepatic tissue homogenate MDA, GSH, SOD, HMGB1, MAPK, RIPK1, and RIPK3 levels were evaluated using ELISA. However, hepatic RAGE and MLKL messenger RNA expression levels using the QRT-PCR technique. Hepatic NF-κB and TNF-α were detected immunohistochemically. Results proved that liraglutide coadministration significantly decreased liver enzymes, MDA, HMGB1, MAPK, RIPK1 RIPK3, RAGE, and MLKL with concomitant increased GSH and SOD in comparison to the correspondent values in VPA-hepatotoxicity group. Conclusions: Liraglutide's protective effects against VPA-induced hepatotoxicity are triggered by ameliorating oxidative stress, inflammation, and necroptosis.
(© 2023 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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