Vitamin D deficiency exacerbates hepatic oxidative stress and inflammation during acetaminophen-induced acute liver injury in mice

Several experiments confirmed that vitamin D3 protected against acetaminophen (APAP)-induced acute liver injury (ALI). This research aimed to evaluate the influence of vitamin D deficiency (VDD) on APAP-induced ALI. In VDD and VDD + APAP groups, mice were fed with VDD diet. In APAP and VDD + APAP groups, mice were intraperitoneally injected with a sublethal dose of APAP (150 mg/kg). A sublethal dose of APAP caused a slight elevation of ALT and AST. Interestingly, APAP-induced elevation of ALT and AST was aggravated in VDD-fed mice. APAP-induced hepatic necrosis was exacerbated in VDD-fed mice. In addition, APAP-induced hepatocyte death, measured using TUNEL assay, was exacerbated in VDD-fed mice. Additional experiment showed that APAP-induced hepatic GSH depletion and lipid peroxidation were exacerbated in VDD-fed mice. Moreover, APAP-induced upregulation of antioxidant genes, such as hepatic heme oxygenase-1 (Ho-1), glutathione peroxidase (Gshpx), superoxide dismutase 1 (Sod1) and catalase enzymes (Cat), was aggravated in VDD-fed mice. Although a sublethal dose of APAP did not cause hepatic inflammation, hepatic proinflammatory cytokines and chemokines, such as Tnf-α, Kc, Mcp-1 and Mip2, were upregulated in VDD-fed mice treated with APAP. These results provide experimental data that VDD exacerbates hepatic oxidative stress and inflammation during APAP-induced ALI.