Glycyrol alleviates the combined toxicity of fumonisin B1 and cadmium in vitro and in vivo

Fumonisin B1 (FB1) is a major food-borne mycotoxin commonly found in maize and maize-based products, while cadmium is one of the most common toxic heavy metals found in food, particularly in wheat and rice. Given the possibility of co-exposure to FB1 and cadmium for consumers, we elevated combined toxicity of FB1 and cadmium using both in vitro and in vivo models. Acute toxicity setting was employed in the present study. Mouse embryonic fibroblast (MEF) and human L02 liver cells were used to determine the in vitro cytotoxicity, while C57BL/6 N mice were used to assess the in vivo toxicity. Results showed that treatment with combination of FB1 (15, 20, 25, 30, 35 mu M) and cadmium (3, 4, 5, 6, 7 mu M) for 24 h led to synergistic cytotoxicity in vitro, and acute treatment with the combination of FB1/cadmium (1.5 mg/kg/60 mg/kg) for 5 days increased liver damage in vivo. Mechanistically, the combined toxicity was associated with elevated activation of IRE1 alpha-JNK pathway. Glycyrol, a representative coumarin compound isolated from licorice, was able to reduce the combination-induced toxicity both in vitro and in vivo through suppression of IRE1 alpha-JNK axis. The combined toxicity of FB1/cadmium should be taken into consideration for performing human health risk assessment of FB1/cadmium exposure.