Host: The Japanese Society of Toxicology
Acrylamide (ACR) is a recognized neurotoxicant which produces effects of neuropathies in humans and experimental animals. Sulforaphane (SFN), a phytochemical mostly found in cruciferous vegetables has been implicated to be protective against inflammation, oxidative stress and several neurologic disorders. The present study therefore sought to investigate the effects of SFN against ACR-induced neuropathy in mice.
Mice were exposed to ACR through drinking water at 0, 200 or 300 ppm and co-treated with SFN at 0 or 25 mg/kg body weight in physiologic saline by subcutaneous injections daily for 28 days. Immunohistochemistry for noradrenergic axons, landing foot spread test, RNA-expression and oxidative stress analysis were conducted following exposure of mice.
Relative to SFN-untreated mice, co-treatment of mice with SFN greatly and dose-dependently protected against ACR-induced neurotoxic effects such as degeneration of noradrenergic axons in the somatosensory cortex and sensorimotor dysfunction. Moreover, neuroprotective effects of SFN were associated with a marked induction of Nrf2 and its downstream antioxidants, NQO1, SOD-1, GST-M, GST-M5, TXNRD1 and MT-1, as well as suppression of proinflammatory cytokine genes TNF-alpha and iNOS along with reduced oxidative stress.
The results suggest that oxidative stress and inflammation mediates the neurotoxicity of ACR and that SFN is a potent inducer of the Nrf2-ARE signaling pathway. Altogether, the present study demonstrates that co-treatment of SFN offered significant protection against ACR-induced neuropathy in mice, probably through activation of Nrf2 and its downstream factors.
