Background: Sepsis-induced liver injury affects about 34.7% of patients and correlates with prognosis. Although vitamin A (VA) and retinol-binding protein 4 (RBP4) are reduced in sepsis, The protective role of VA remains unknown. This study aimed to explore the effects of VA and mechanisms in septic liver injury. Methods: Cecal ligation puncture (CLP) was performed in male C57BL/6 mice. After 24h, retinol (ROL, 0.01, 0.1, 1 mg/kg), RBP4 (0.5 mg/kg), or their combinations were administered. Liver/serum samples collected 24h later assessed injury (histopathology, function) and RIG-I/RIPK1/RIPK3/MLKL expression via IHC, WB, and RT-qPCR. In LPS-stimulated AML-12 cells, ROL, RBP4, ROL+RBP4, or retinoic acid (RA) effects were evaluated. Results: CLP mice showed decreased serum ROL at 12h (lowest at 24h), while RBP4 transiently rose at 3h before declining (lowest at 24h). ROL (1 mg/kg) + RBP4 significantly improved survival, reduced liver injury (low Knodell scores), and suppressed RIG-I/TNF-α/RIPK1-RIPK3-MLKL necroptosis. LPS reduced RBP4 in AML-12 cells (p<0.001); ROL+RBP4 and RA alleviated damage via inhibiting necroptosis. Conclusion: VA may exert hepatoprotection by suppressing RIG-I, reducing TNF-α, and inhibiting RIPK1/RIPK3/MLKL-mediated necroptosis.
Liu et al. (Mon,) studied this question.