Mesenchymal stem cells ameliorate oxidative stress, inflammation, and hepatic fibrosis via Nrf2/HO-1 signaling pathway in rats
2021
Khadrawy, Sally M. | Mohamed, Hanaa M. | Mahmoud, Ayman M.
Liver fibrosis occurs in most types of chronic liver diseases and can develop into cirrhosis and liver failure. Bone marrow-derived mesenchymal stem cells (BMSCs) showed promising effects in the treatment of fibrosis. This study evaluated the possible role of Nrf2/HO-1 signaling in the ameliorative effect of BMSCs against carbon tetrachloride (CCl₄)-induced liver fibrosis, oxidative stress, and inflammation in rats. Hepatic fibrosis was induced by subcutaneous injection of CCl₄ twice per week for 6 consecutive weeks and rat BMSCs were administered intravenously. After 4 weeks, the rats were sacrificed, and samples were collected for analysis. CCl₄-intoxicated rats showed elevated serum transaminases, ALP, γGT, bilirubin and pro-inflammatory cytokines, and decreased albumin. Hepatic NF-κB p65 and malondialdehyde (MDA) were significantly increased, and cellular antioxidants were decreased in CCl₄-intoxicated rats. BMSCs ameliorated liver function markers, suppressed MDA, NF-κB p65, and inflammatory cytokines, and enhanced antioxidants in the liver of CCl₄-intoxicated rats. BMSCs were engrafted within the liver tissue and prevented histological alterations and collagen accumulation induced by CCl₄. In addition, BMSCs upregulated hepatic Nrf2 and HO-1 expression in CCl₄-intoxicated rats. In conclusion, this study provides evidence that BMSCs suppress oxidative stress, inflammation, and liver fibrosis through a mechanism involving activation of the Nrf2/HO-1 signaling.
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