Plasmalogens Reversed\nOxidative Stress and Inflammatory\nResponse Exacerbated by Damage to Cell Membrane Properties in Acute\nLiver Injury

Background: In acute liver injury (ALI), cell membrane\ndamage could\ninduce an inflammatory response and oxidative stress. As a membrane\nglycerophospholipid, plasmalogens (PLS) are crucial in regulating\nthe cell membrane properties and exhibit beneficial effects in various\nliver diseases. However, the specific regulatory effects of PLS in\nthe ALI remain unknown. Methods: We utilized CCl<sub>4</sub> to induce\nALI in AML12 hepatocytes and C57BL/6J mice and examined oxidative\nstress indicators and inflammatory cytokine levels. Our study further\nvalidated the effect of PLS on cell membrane integrity by Lactate\nDehydrogenase (LDH) release assay and Dil/Calcein assay, and molecular\ndynamics (MD) simulations were employed to elucidate the molecular\nmechanisms by which PLS affected cell membranes. Results: PLS attenuated\nhepatocyte damage both in vivo and in vitro. Moreover, PLS increased\nlevels of SOD, GSH, and CAT and inhibited the production of malondialdehyde.\nPLS succeeded in decreasing proinflammatory cytokines (TNF-α,\nIL-1β, and IL-6) while increasing anti-inflammatory cytokines\n(IL-10). Furthermore, PLS effectively maintained the cell membrane\nintegrity. The MD simulations well explained the molecular mechanisms:\na high level of PLS modulated the cell membrane properties, enabling\nthem to be more flexible, elastic, and less prone to rupture. Conclusions:\nOur study illustrated the effect and molecular mechanisms of PLS against\nALI, potentially broadening its application in liver diseases.