Altered lipid metabolism and ferroptosis in sodium hydroxide-induced skin burns: a comprehensive rat model-based...

Sodium hydroxide (NaOH) is known to cause severe injuries through lipid saponification; however, the mechanisms underlying NaOH-induced skin injuries, particularly their effects on lipid metabolism and ferroptosis, are unclear. Here, we aimed to elucidate these mechanisms based on lipid profile evaluations and ferroptosis occurrence.

We used experimental rat models of NaOH-induced skin burns (skin exposed to 0.05% NaOH for 90 or 180 s) alongside a sham-treated control group. Skin morphology and integrity were assessed. Differentially expressed lipid profiles were monitored via untargeted lipidomics. Oxidative stress, lipid peroxidation, and iron metabolism were also assessed. The expression of ferroptosis-associated genes, including acyl-CoA synthetase long-chain family member 4 (ACSL4), lysophosphatidylcholine acyltransferase 3 (LPCAT3), and glutathione peroxidase 4 (GPX4), was analysed using immunohistochemical and quantitative reverse transcription-polymerase chain reaction analyses.

NaOH exposure for 90 and 180 s caused second- and third-degree burns, respectively, leading to elevated and reduced levels of polyunsaturated and monosaturated fatty acid phospholipids, respectively. Both groups showed significant increases in reactive oxygen species, ferrous iron, and malondialdehyde levels and significant decreases in glutathione levels. ACSL4 and LPCAT3 expression increased, and GPX4 expression decreased.

NaOH-induced skin burns disrupt skin appendages, resulting in lipid metabolism alterations and ferroptosis induction. These findings could provide valuable insights for elucidating the precise mechanisms underlying ferroptosis in the context of NaOH burns and for identifying potential therapeutic strategies.