Danshensu derivative ADTM ameliorates CCl4‑induced acute liver injury in mice through inhibiting oxidative stress and apoptosis

Abstract

Previous studies reported a novel danshensu derivative (R)-(3,5,6-Trimethylpyrazinyl) methyl-2-acetoxy-3-(3,4-diacetoxyphenyl) propanoate (ADTM), which conferred cardioprotective, neuroprotective and anti-thrombotic effects. Here we aim to investigate the hepatoprotective effect of ADTM on acute liver injury caused by carbon tetrachloride (CCl4) and the underlying molecular mechanisms. ADTM (30 and 60 mg/kg) was given to mice by gavage for two weeks. At the last day mice were injected with 0.3% CCl4, 10 mL/kg, ip for 24 h. Clinical and histological chemistry assays were performed to assess liver injury. Moreover, hepatic oxidative stress and apoptosis related markers were determined by western blotting. As a result, ADTM significantly protected against CCl4-induced liver injury by the decrease of elevated serum transaminases and liver index, and the attenuation of histopathological changes in mice. In addition, ADTM remarkably alleviated hepatic oxidative stress (MDA contents and SOD activity) and apoptosis. Further studies revealed that ADTM significantly inhibited the CCl4-induced upregulation of Bax/Bcl-2, increased the CCl4-induced decrease of AKT phosphorylation and inhibited the expression level of NF-κB p65 in CCl4-intoxicated mice. These findings suggest that ADTM possesses the potential protective effects against CCl4-induced liver injury in mice by exerting antioxidative stress and antiapoptosis.