Host: The Japanese Society of Toxicology
Acrylamide (ACR) is an electrophile which has been used extensively in industry and is also formed unintentionally in food substances cooked or processed at high temperatures, such as potato chips or coffee through Maillard reaction. Acrylamide has been recognized as a potent neurotoxin which is known to cause neuropathy or encephalopathy in humans and experimental animals. As a measure of protection against neurotoxicity, the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) has been identified to be a master regulator of the cellular defense system which activates antioxidant and cytoprotective genes. However, knowledge about the exact mechanistic roles of NRF2 in ACR-induced neurotoxicity remains poorly understood. This study therefore seeks to investigate the roles of NRF2 in attenuating ACR induced neurotoxicity.
Groups of 15 male Nrf2-knockout mice and 15 male wild-type (WT) C57BL/6J mice were each divided into three groups of five and daily exposed to ACR at 0, 67 or 200 ppm in drinking water for 28 days.
Landing foot splay, a major endpoint marker of neurotoxicity, showed a significantly increased values in the NRF2-knockout mice relative to WT mice at the same exposure levels. NRF2-knockout mice also showed a significantly reduced total brain and cerebellum weight compared to the WT mice. The results suggest increased susceptibility to ACR-induced neurotoxicity in mice lacking the NRF2 gene. In conclusion, NRF2 is able to attenuate the effect of ACR-induced neurotoxicity in mice.