Attenuating effects of allantoin on oxidative stress in a mouse model of nonalcoholic steatohepatitis

Abstract

Background and purpose: Nonalcoholic steatohepatitis (NASH) is considered a common and serious liver disease, which develops into cirrhosis, fibrosis, and even hepatocellular carcinoma. Oxidative stress is identified as an important factor in the induction and promotion of NASH. Allantoin is a natural and safe compound and has notable effects on lipid metabolism, inflammation, and oxidative stress. Therefore, this study was aimed to assess the role of allantoin on the oxidative stress and SIRT1/Nrf2 pathway in a mouse model of NASH. Experimental approach: C57/BL6 male mice received saline and allantoin (saline as the control and allantoin as the positive control groups). NASH was induced by a methionine-choline deficient diet (MCD). In the NASH-allantoin (NASH-Alla) group, allantoin was injected for 4 weeks in the mice feeding on an MCD diet. Afterward, histopathological, serum, oxidative stress, and western blot evaluations were performed. Findings/Results: We found NASH provided hepatic lipid accumulation and inflammation. Superoxide dismutase (SOD) and glutathione (GSH) levels decreased, lipid peroxidation increased, and the expression of SIRT1 and Nrf2 downregulated. However, allantoin-treatment decreased serum cholesterol, ALT, and AST. Liver steatosis and inflammation were improved. Protein expression of SIRT1 and Nrf2 were upregulated and SOD, CAT, and GSH levels increased and lipid peroxidation decreased. Conclusion and implications: It seems that the antioxidant effects of allantoin might have resulted from the activation of SIRT1/Nrf2 pathway and increase of cellular antioxidant power.

Lemon Balm and Corn Silk Extracts Mitigate High-Fat Diet-Induced Obesity in Mice

“…Our supplementary in vitro results indicated that rosmarinic acid could scavenge 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical in a concentration-dependent manner (IC 50 , 2.25 ± 0.03 μg/mL). However, allantoin, up to 300 μg/mL, did not remove the radical produced from DPPH ( Figure S1 ), which are parallel with previous observation that rosmarinic acid and allantoin exhibit (in)direct antioxidant activities [ 26 , 27 , 28 ]. Rosmarinic acid is a derivative of hydroxycinnamic acid in which caffeic acid and 3,4-dihydroxyphenyllactic acid are linked by an ester bond.…”

Integrated 16S rRNA sequencing and nontargeted metabolomics analysis to reveal the mechanisms of Yu-Ye Tang on type 2 diabetes mellitus rats

“…The main active component of Dioscorea oppositifolia L. includes allantoin, which has been demonstrated with protective effects on pancreas β-cells in metabolic dysfunction model ( 12 ). Allantoin can also improve nonalcoholic steatohepatitis disease by activating the SIRT1/Nrf2 pathway, increasing the activities of antioxidant enzymes, and reducing lipid peroxidation ( 13 ). Astragaloside is the main component of Astragalus mongholicus Bunge, and several studies have confirmed that astragaloside could reduce inflammation and oxidative stress in animal model of diabetes ( 14 , 15 ).…”