Plasmalogens Reversed Oxidative Stress and Inflammatory Response Exacerbated by Damage to Cell Membrane Properties in Acute Liver Injury

Background: In acute liver injury (ALI), cell membrane damage could induce an inflammatory response and oxidative stress. As a membrane glycerophospholipid, plasmalogens (PLS) are crucial in regulating the cell membrane properties and exhibit beneficial effects in various liver diseases. However, the specific regulatory effects of PLS in the ALI remain unknown. Methods: We utilized CCl₄ to induce ALI in AML12 hepatocytes and C57BL/6J mice and examined oxidative stress indicators and inflammatory cytokine levels. Our study further validated the effect of PLS on cell membrane integrity by Lactate Dehydrogenase (LDH) release assay and Dil/Calcein assay, and molecular dynamics (MD) simulations were employed to elucidate the molecular mechanisms by which PLS affected cell membranes. Results: PLS attenuated hepatocyte damage both in vivo and in vitro. Moreover, PLS increased levels of SOD, GSH, and CAT and inhibited the production of malondialdehyde. PLS succeeded in decreasing proinflammatory cytokines (TNF-α, IL-1β, and IL-6) while increasing anti-inflammatory cytokines (IL-10). Furthermore, PLS effectively maintained the cell membrane integrity. The MD simulations well explained the molecular mechanisms: a high level of PLS modulated the cell membrane properties, enabling them to be more flexible, elastic, and less prone to rupture. Conclusions: Our study illustrated the effect and molecular mechanisms of PLS against ALI, potentially broadening its application in liver diseases.