Canagliflozin attenuates thioacetamide-induced liver injury through modulation of HMGB1/RAGE/TLR4 signaling pathways.

Autor: Abdelmageed ME; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, 35516 Mansoura, Egypt. Electronic address: marwaelsayed90@mans.edu.eg., Abdelrahman RS; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, 35516 Mansoura, Egypt; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Taibah University, Al-Madina Al-Munawwarah 30001, Saudi Arabia.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2023 Jun 01; Vol. 322, pp. 121654. Date of Electronic Publication: 2023 Apr 05.
DOI: 10.1016/j.lfs.2023.121654
Abstrakt: Thioacetamide (TAA), a classic liver toxic compound, is used to establish experimental models of liver injury via induction of inflammation and oxidative stress. The current study was employed to explore the effects of canagliflozin (CANA), a sodium glucose cotransporter 2 (SGLT-2) inhibitor and antidiabetic agent, on TAA-induced acute liver injury.
Methods: A rat model of acute hepatic injury was established using single intraperitoneal injection of TAA (500 mg/kg) and rats received CANA (10 and 30 mg/kg, orally) once daily for 10 days prior to TAA challenge. Liver function, oxidative stress, and inflammatory parameters were measured in serum and hepatic tissues of rats.
Results: Elevated levels of liver enzymes, hepatic malondialdehyde (MDA), and serum lactate dehydrogenase (LDH) were significantly attenuated by CANA. CANA also increased hepatic superoxide dismutase (SOD) and glutathione (GSH). Hepatic levels of high-mobility group box 1 (HMGB1), toll like receptor4 (TLR4), receptor for advanced glycation end products (RAGE), and pro-inflammatory cytokines (IL-6, and IL-1β) were normalized with CANA. Additionally, Hepatic expression of p-JNK/p-p38 MAPK was significantly attenuated by CANA compared to TAA-treated rats. CANA also decreased hepatic immunoexpression of NF-κB and TNF-α and attenuated hepatic histopathological alterations via reduction of inflammation and necrosis scores and collagen deposition. Moreover, mRNA expression levels of TNF-α and IL-6 were reduced upon CANA treatment.
Conclusion: CANA attenuates TAA-prompted acute liver damage, via suppressing HMGB1/RAGE/TLR4 signaling, regulation of oxidative stress and inflammation pathways.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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