Protective Effects of Resveratrol on Cytotoxicity of Mouse Hepatic Stellate Cells Induced by PM 2.5.

The atmosphere's fine particulate matter (PM_2.5) can enter the liver through the circulatory system, leading to hepatic inflammation and fibrosis. As a non-flavonoid polyphenolic compound, resveratrol (RES) has anti-oxidant, anti-inflammatory and hepatoprotective effects, but the molecular mechanisms of liver fibrosis induced by PM_2.5 exposure are still limited. In this study, we established an in vitro cell model to investigate the intervention effect of RES with different concentrations (5 and 20 μmol/mL) on mouse hepatic stellate cells (mHSCs) injury induced by PM_2.5 (100 μg/mL). We determined the cell viability in mHSCs after treatment with PM_2.5 or/and RES for 24 h. We investigated the intracellular oxidative stress by detecting the changes in reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) and lactate dehydrogenase (LDH) levels. We also measured the protein expressions of fibrosis-related genes (α-SMA, Collagen I and Collagen III) and key genes (SIRT1, NF-κB, NLRP3, Cleaved-Caspase1, IL-1β) in the NLRP3 pathway in mHSCs exposed to PM_2.5 with or without RES. The results showed that (1) PM_2.5 has cytotoxic effects on mHSCs, whereas RES (5 μmol/L and 20 μmol/L) inhibited PM_2.5-induced cytotoxicity and LDH leakage; (2) RES effectively reduces ROS and MDA production caused by PM_2.5 while concurrently enhancing SOD levels, thereby improving cellular anti-oxidant capacity; (3) the expression of α-SMA, Collagen I and Collagen III were notably downregulated in the PM_2.5 plus RES treatment group compared to the PM_2.5-exposed group; (4) RES significantly increased SIRT1 expression and decreased the expression of NF-κB, NLRP3, Cleaved-Caspase1 and IL-1β in mHSCs exposure to PM_2.5 compared to the PM_2.5 group. These results demonstrate that RES can up-regulate SIRT1 and mitigate PM_2.5-induced fibrosis by suppressing oxidative stress in mHSCs and the SIRT1/NF–κB/NLRP3 pathway activated by PM_2.5. [ABSTRACT FROM AUTHOR]