Immunopharmacology and immunotoxicology · 2026
Omarigliptin attenuates thioacetamide-induced hepatic fibrosis in rats by activating SIRT1/Nrf2 and inhibiting NF-κB/TGF-β1 pathways.
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Alarifi Abdulaziz, Qadri Marwa, Almarghalani Daniyah A, Alquraini Ali, Alkholifi Faisal K, Alomar Fadhel A, Alasmari Moudi M, Shokry Aya A, Moustafa Passant E, Fayed Hany M, Shabana Marwa E
Аннотация
BACKGROUND: Hepatic fibrogenesis, a reversible but serious condition characterized by excessive extracellular matrix deposition, can progress to cirrhosis. This study examined the multi-mechanistic protective effects of the dipeptidyl peptidase-4 inhibitor Omarigliptin (OMR) against thioacetamide (TAA)-induced hepatic fibrogenesis.
METHODS: Rats were grouped into control, TAA (100 mg/kg, IP, twice weekly, 6 weeks), and TAA plus OMR (2.5 or 5 mg/kg/day, orally, last 4 weeks).
RESULTS: TAA induced substantial liver damage, evidenced by elevated serum alanine aminotransferase, aspartate aminotransferase, triglycerides, and cholesterol, alongside decreased albumin and total protein. TAA further triggered oxidative stress, depleting glutathione and superoxide dismutase, raising malondialdehyde, and suppressing the SIRT1/Nrf2 axis. Additionally, TAA elevated pro-inflammatory (TNF-α, IL-1β, NF-κB p65) and pro-fibrotic (TGF-β1, α-SMA) markers, paralleled by histopathological injury and increased fibrosis scores. OMR treatment, particularly at 5 mg/kg, attenuated TAA-induced liver dysfunction, oxidative stress, inflammation, and fibrosis.
CONCLUSION: OMR exerts hepatoprotective and anti-fibrotic effects against TAA-induced injury by activating SIRT1/Nrf2 and suppressing NF-κB and TGF-β1 signaling. These multi-mechanistic actions support its repurposing for fibrotic liver diseases.
METHODS: Rats were grouped into control, TAA (100 mg/kg, IP, twice weekly, 6 weeks), and TAA plus OMR (2.5 or 5 mg/kg/day, orally, last 4 weeks).
RESULTS: TAA induced substantial liver damage, evidenced by elevated serum alanine aminotransferase, aspartate aminotransferase, triglycerides, and cholesterol, alongside decreased albumin and total protein. TAA further triggered oxidative stress, depleting glutathione and superoxide dismutase, raising malondialdehyde, and suppressing the SIRT1/Nrf2 axis. Additionally, TAA elevated pro-inflammatory (TNF-α, IL-1β, NF-κB p65) and pro-fibrotic (TGF-β1, α-SMA) markers, paralleled by histopathological injury and increased fibrosis scores. OMR treatment, particularly at 5 mg/kg, attenuated TAA-induced liver dysfunction, oxidative stress, inflammation, and fibrosis.
CONCLUSION: OMR exerts hepatoprotective and anti-fibrotic effects against TAA-induced injury by activating SIRT1/Nrf2 and suppressing NF-κB and TGF-β1 signaling. These multi-mechanistic actions support its repurposing for fibrotic liver diseases.