Abstract
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. MethodsA 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. ResultsElevated 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. ConclusionCANA attenuates TAA-prompted acute liver damage, via suppressing HMGB1/RAGE/TLR4 signaling, regulation of oxidative stress and inflammation pathways.
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