Ertugliflozin, a SGLT-2 Inhibitor, Guards Against Thioacetamide-induced Liver Fibrosis: The Nrf2/HO-1 and TLR4/ TGF-β1 Pathways | ||
| Journal of Applied Veterinary Sciences | ||
| Article 5, Volume 10, Issue 3, July 2025, Pages 34-47 PDF (559.58 K) | ||
| Document Type: Original Article | ||
| DOI: 10.21608/javs.2025.372525.1573 | ||
| Authors | ||
| Nourhan Hussien Hassan* 1; Gehan M. Kamel1; Hany M. Fayed2; Reda M.S. Korany3; Amer Ramadan1 | ||
| 1Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Egypt | ||
| 2Department of Pharmacology, Medical Research and Clinical Studies Institute, National Research Centre, Giza, Egypt | ||
| 3Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Egypt; Department of Pathology, Faculty of Veterinary Medicine, Egyptian- Chinese University, Egypt | ||
| Abstract | ||
| Hepatic fibrogenesis is considered an epidemic health problem since it can lead to several insults that can be fatal. Ertugliflozin (Ertu), an inhibitor of the sodium-glucose cotransporter-2 (SGLT2), is one of the most recent anti-diabetic medications used to treat type 2 diabetes mellitus (T2DM). In a variety of human and animal models, SGLT2 inhibitors demonstrated anti-inflammatory, anti-fibrotic, and antioxidant qualities. Consequently, we designed the present investigation to clarify the preventive role of ertugliflozin in male rat liver fibrosis brought on by thioacetamide (TAA) as well as the anticipated mechanisms. 24 rats were divided into four groups: “a control group, “TAA group” (received intraperitoneal injections of 100 mg/kg b.wt. twice a week for six weeks), and "TAA + Ertu" groups (received oral Ertu at doses of 5 and 10 mg/kg b.wt. for four weeks in addition to TAA injections). Ertugliflozin promoted hepatic antioxidant effects by considerably increasing HO-1, Nrf2 protein and mRNA expression, GSH and SOD levels, and lowering hepatic MDA content. It also greatly reduced TAA-induced changes in liver function measures. Additionally, ertugliflozin suppressed the elevated levels of “PI3K, TGF-β1, α SMA, and caspase3” and enhanced the hepatic anti-inflammatory state by declining the pro-inflammatory cytokines “TNF-α, IL-6, and TLR4” levels. Histological examination showed that ertugliflozin significantly inhibited the liver alterations caused by TAA. Our findings imply that ertugliflozin’s hepatoprophylactic effects may be mediated by improving antioxidant capacities and reducing inflammatory signals by modifying the Nrf2/HO-1 and TLR4/TGF-β1 pathways. | ||
| Keywords | ||
| Ertugliflozin; Liver fibrosis; Nrf2/HO-1 pathway; Thioacetamide; TLR4 | ||
| References | ||
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