Tamoxifen Prevents D-galactosamine/Lipopolysaccharide-Induced Murine Acute Hepatic Failure through Inhibition of Oxidative Stress and Mmd-2 Upregulation

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.

Protective effects of tamoxifen and raloxifene on apoptosis and oxidative stress in the kidney and liver of ovariectomized rats

“…Our results were in agreement with previous reports showing that RAL significantly reduced MDA levels and significantly increased GSH levels in liver and kidney tissues. However, while there are limited animal studies showing TAM to be an antioxidant (Moreira et al 2005;Zhang et al 2007;Yazğan et al 2016;Yazğan and Nazıroğlu, 2017), there also are reports demonstrating it to be oxidant and cytotoxic (Parves et al 2006;Nazarewicz et al 2007;Gong et al 2018). In this study, we found that TAM has a therapeutic effect on OVinduced oxidative stress, similar to our previous studies.…”

The Water Extract of Ampelopsis grossedentata Alleviates Oxidative Stress and Intestinal Inflammation

“…The mice were housed in a controlled environment with a consistent temperature, humidity, and light–dark cycle. After acclimatizing for one week, the mice were randomly divided into six groups ( n = 8) ( Figure 1 ), including the positive control (NAC) group, which was administered N-acetylcysteine (NAC) at a dose of 300 mg/kg/day [ 19 ]; the blank (control) and model (LPS) group, which was administered saline by oral gavage; and the low-, medium-, and high-dose WEA (WEA-L, WEA-M, WEA-H) groups were administered WEA at concentrations of 50, 100, and 200 mg/kg/day, respectively. To evaluate the safety and efficacy of WEA, fresh fecal samples were collected at the end of the experimental period and stored at −80 °C for subsequent analysis.…”