ABSTRACT
Oxidative stress is considered one of the major mechanisms underlying lipopolysaccharide (LPS)-induced acute liver failure (ALF). Tamoxifen has been reported to ameliorate LPS-induced ALF via the induction of monocyte to macrophage differentiation-associated 2 (Mmd-2). Whether antioxidant effects are involved remains unknown. Mice were given tamoxifen (TAM) once a day for 3 days. Twelve hours later, d-galactosamine (GaIN) and LPS were injected intraperitoneally to induce ALF. N-Acetylcysteine (NAC) was administered immediately after ALF induction as a positive control. The results showed that serum transaminases increased and hepatic antioxidants decreased significantly in the model group. ALF was alleviated markedly by TAM or NAC treatment. This demonstrated that ALF may be associated with excessive oxidative stress caused by decreased expression of antioxidant enzymes. Both TAM and NAC increased the levels and activity of these antioxidant enzymes significantly (p < 0.05). Hepatic Mmd-2 expression was downregulated in the control group while remaining stable or exhibiting elevated levels in the TAM or NAC groups. The results indicate that TAM may protect mice from GaIN/LPS-induced ALF through increased activity of antioxidant enzymes and upregulation of Mmd-2 expression.
Acknowledgments
We would like to gratefully thank Master Fang Peng from the Affiliated Ganzhou Hospital of Nanchang University for the assistance of IHC and Dr. Yinghua Xu from National Institutes for Food and Drug Control for the careful review of this manuscript.
Conflicts of interest
All the procedures of animal experiments in this study are approved by the Ethical committee of the Affiliated Ganzhou Hospital of Nanchang University. The authors contributing to this work do not have any conflicts of interest.