Diallyl trisulfide protects against concanavalin A-induced acute liver injury in mice by inhibiting inflammation, oxidative stress and apoptosis

Abstract

Aims: To investigate the protective effects and underlying mechanisms of diallyl trisulfide (DATS) against acute liver injury induced by concanavalin A (Con A).

Materials and methods: DATS (20, 40, 80 mg/kg) were gavaged to ICR mice 1 h before Con A (20 mg/kg) tail vein injection. The survival rate of mice, alterations of serum biochemical markers and liver histopathology were measured to evaluate the protective effects of DATS at 24 h after Con A exposure. The indexes of inflammation, oxidative stress and apoptosis were determined to explore the possible mechanisms.

Key findings: DATS pretreatment increased survival rate of mice in a dose-dependent manner, inhibited the increase of liver-to-spleen ratio and serum liver injury markers, and attenuated liver pathological damage induced by Con A. Further study showed that DATS pretreatment inhibited the activation of Kupffer cells/macrophages, release of tumor necrosis factor-α (TNF-α) and Caspase-1-dependent inflammation induced by Con A. Moreover, DATS pretreatment alleviated the oxidative stress induced by Con A, which was evidenced by increased superoxide dismutase (SOD) and catalase (CAT) activities and decreased malondialdehyde (MDA) content in DATS and Con A co-treated mice compared with Con A alone group. Finally, DATS pretreatment reduced eosinophilic body formation, TUNEL positive staining and increased Bcl-2/Bax ratio in liver of Con A-injected mice, indicating attenuated apoptosis.

Significance: Collectively, the results suggest that DATS displays potent protective effects against Con A-induced acute liver injury in mice possibly through inhibition of inflammation, oxidative stress and apoptosis.

Keywords: Acute liver injury; Apoptosis; Concanavalin A; Diallyl trisulfide; Inflammation; Oxidative stress.