Cerium oxide nanoparticles attenuate hepatic failure via blocking TGF-β/Smads and upregulating Nrf2/HO-1 signaling pathways in liver fibrosis rat model

Abstract

T his article is aimed at assessing the anti-fibrotic action of plant-based fabricated cerium oxide nanoparticles (CeO 2 NPs). The Carissa carandas aerial parts methanolic extract was utilized to prepare CeO 2 NPs, where the dispersal of particle size distribution and zeta potential value was 61.9 nm and − 18.94 mV, respectively, verifying the successful synthesis of CeO 2 NPs. In rats, CeO 2 NPs were intravenously injected at doses of 0.1 and 0.5 mg/kg twice a week for a month, in parallel with thioacetamide (TAA, 200 mg/kg, i.p). Our findings revealed that CeO 2 NPs alleviated the alteration in serum GPT, GOT, ALP, total bilirubin, albumin, and total protein levels induced by TAA. Additionally, the hepatic oxidative insult due to TAA was inferred by elevation in malondialdehyde and reduction of glutathione content, which in combination with downregulation of SIRT1, Nrf2, and HO-1 in hepatic tissues was improved by CeO 2 NPs. A clear repression in hepatic fibrosis was observed in CeO 2 NP-treated groups as demonstrated by significant downregulation in TGF-β1 and p-Smad 2 and 3 proteins and COL1A1, MMP-2, and α-SMA expressions in hepatic tissues. The histopathological outcomes exhibited a considerable accumulation of collagen fibers in hepatocytes in TAA-challenged rats, which was ameliorated by CeO 2 NPs. Also, CeO 2 NPs dampened the death of hepatic cells via blocking caspase 3 activation as indicated by the immunohistochemical results. The in silico investigations documented the powerful binding affinities of TGF-β1, COL1A1, MMP-2, p-Smad2, p-Smad3, SIRT1, Nrf2, and HO-1 proteins with CeO 2 NPs. In conclusion, this study emphasized the efficacy of CeO 2 NPs as a potent anti-fibrotic agent through upregulating SIRT1/Nrf2/HO-1 and downregulating TGF-β1/Smads pathways.

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