Restoring mitochondrial function and normalizing ROS-JNK/MAPK pathway exert key roles in glutamine ameliorating bisphenol A-induced intestinal injury

Abstract

Bisphenol A (BPA) is toxic to the reproductive and nervous system, even carcinogenetic in humans and animals. However, few studies focused on effects of BPA on the intestinal tract. Here, we detected BPA-induced injuries on intestinal mucosa and explored a reliable approach to counteract BPA effects. C57BL/6J mice were gavage BPA or BPA accompanied with ingestion of 4% (w/w) of glutamine for 4-wks. In vitro, IEC-6 cells were treated with 0.4 mmol/L BPA for 6 hours mimicking acute injury and 0.2 mmol/L BPA for 12 hours followed with or without the inclusion of 4 mmol/L glutamine for 12 hours to determine cell renewal, mitochondrial function and ROS-JNK/MAPK pathway upon moderate BPA exposure. As results, BPA exposure caused severe intestinal injury, and disturbed intestinal epithelial cell proliferation and apoptosis, accompanied with mitochondrial malfunction and activated JNK/MAPK pathway as well. Notably, glutathione metabolism was implicated in BPA-induce injury. Glutamine could well rescue cell renewal and mitochondrial function from BPA exposure-induced injuries. In conclusion, we demonstrated impaired effect of BPA exposure on intestinal functions, which could be well counteracted by glutamine partly via restoring mitochondrial function and normalizing ROS-JNK/MAPK pathway. Thereby, we provided a novel application of glutamine to rescue intestinal injury.

Keywords: apoptosis; glutathione; intestinal mucosa; mitochondrial malfunction.