Alleviative Effect of Threonine on Cadmium-Induced Liver Injury in Mice.

Abstract

As a toxic trace element commonly found in food, cadmium (Cd) can cause severe liver injury. Our previous study showed that threonine (Thr) could significantly alleviate Cd toxicity in yeast. To investigate the effect of Thr on Cd-induced liver injury in mice, twenty-four mice were randomly divided into four groups: control, Cd, and low/high dose of Thr-treatment groups (0.04 and 0.08mmol/kg/day, respectively). After 7days of continuous treatment, the alleviative effect of Thr on liver injury in Cd-exposed mice was assessed. The results showed that Thr significantly reduced the elevation of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in Cd-exposed mice. Histological analysis showed that Thr decreased Cd-induced hepatic steatosis, zonal necrosis, and inflammatory cell infiltration. Thr also reduced the Cd-induced malondialdehyde (MDA) and O2- levels and restored superoxide dismutase (SOD) and catalase (CAT) activities in the liver. Further investigation showed that Thr significantly suppressed Cd-induced inflammatory response (tumor necrosis factor-α and interleukin-6) and restored the level of anti-apoptotic protein (Blc-2) but inhibited the elevation of pro-apoptotic proteins (Bax and caspase-3), as well as the activation of the PI3K/AKT signaling pathway in Cd-exposed mice. In conclusion, Thr alleviated Cd-induced liver injury through reducing Cd-induced oxidative stress, inflammation, and attenuating hepatocyte apoptosis via PI3K/AKT-related signaling pathway.