Lipopolysaccharides Pretreatment Reduces Acetaminophen-induced Acute Liver Injury In Mice

Objective Paracetamol(Acetaminophen, APAP) is a commonly used non-steroidal anti-inflammatory drug. The over dose APAP can cause acute liver injury. LPS(lipopolysaccharides, LPS) is a major component of the cell wall of Gram-negative bacteria, trace amounts of LPS can activate monocyte-macrophage cell systems, promote the release of cytokines, activation and production of the antibody. On the basis of this study,we intends to establish an animal model of APAP-induced acute liver injury in mice, and investigate the protective effect of acute liver injury caused by APAP on the low-dose LPS pretreatment.Methods(1) To observe the effects of LPS on APAP-induced acute liver injury in mice survival, 20 ICR male mice were randomly divided into APAP group and LPS + APAP group. After fasting 10 h, APAP group were injected APAP(300mg / kg); LPS + APAP group were injected intraperitoneally LPS(50μg / kg), 3h later giving APAP(300mg / kg). After administration, close observation of the mice survival situation, 72 h later, measuring biochemical indicator.(2) In order to investigate the protective effect of LPS in mice with acute liver injury, ICR male mice were randomly divided into APAP 0h, 0.5h, 6h, 12 h, 24 h, 72 h group and LPS + APAP 0h, 0.5h, 6h, 12 h, 24 h, 72 h groups(n=6). After fasting 10 h, APAP group were intraperitoneally injected with APAP(300mg / kg); LPS + APAP group were injected with LPS(50μg/kg) 3h before APAP(300mg/kg). After administration, drawn at the corresponding time point(0h, 0.5h, 6h, 12 h, 24 h, 72h) and measure serum ALT and other indicator.Results(1) The survival rate of APAP group was 50% within 72h; while LPS + APAP have no deaths.(2) With prolonged duration of action of the drug, the liver coefficient and ALT values of APAP group gradually increased, reached the highest point in 24 h.The group of LPS+APAP increased to the highest values at 0.5h. The increase was significantly lower than APAP group, APAP group ALT peak was 6169.08 ± 4048.50 U / L, LPS + APAP group was 584.92 ± 515.59 U / L, there was a significant difference between the two(P <0.01).(3) The necrotic area ratio of APAP 24 hgroup was 65.64 percent; while the LPS + APAP 24 h group was 28.44%(P <0.01).(4) LPS + APAP group 0h point GSH value was 0.90 ± 0.15μmol/g, the control group was 0.92 ± 0.20μmol/g, no significant difference between the two. When 0.5h, the GSH value of APAP group was 0.36μmol/g, and the LPS + APAP group was 0.37μmol/g, there was a significant difference(P <0.01) compared with the control group.Conclusion Low-dose LPS pretreatment on APAP-induced acute liver injury has a significant protective effect, the specific mechanism is not clear. This protective effect may be produced by LPS activation of its immune response, inhibition of GSH depletion related to the downstream mechanism.