MAPKs and NF‐κB‐mediated acrylamide‐induced neuropathy in rat striatum and human neuroblastoma cells SY5Y

Abstract

Acrylamide (ACR) is a potent neurotoxin that can be produced during hightemperature food processing, but the underlying toxicological mechanism remains unclear. In this study, the detrimental effects of ACR on the striatal dopaminergic neurons and the roles of mitogen-activated protein kinases (MAPKs) and nuclear factor κB (NF-κB) in ACR-induced neuronal apoptosis were investigated. Acute ACR exposure caused dopaminergic neurons loss and apoptosis as revealed by decreased tyrosine hydroxylase (TH)-positive cells and TH protein level and increased terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells in the striatum. ACR-decreased glutathione content, increased levels of malondialdehyde, proinflammatory cytokines tumor necrosis factor α, and interleukin 6. In addition, nuclear NF-κB and MAPKs signaling pathway with c-Jun N-terminal kinase (JNK) and p38 were activated by ACR. Specific inhibitors were used to explore the roles of MAPKs and NF-κB pathways in ACR-induced apoptosis in SH-SY5Y cells. Pretreatment with JNK-specific inhibitors SP600125 markedly upregulated the reduced B-cell lymphoma 2 (Bcl-2) content and downregulated the increased Bcl-2-associated X protein (Bax) level and thereby eventually reduced the proportions of early and late apoptotic cells induced by ACR, while p38 suppression by SB202190 only reversed the decrease in Bcl-2 expression. Inhibition of NF-κB by BAY 11-7082 markedly upregulated Bax level and decreased Bcl-2 expression, and eventually increasing the proportions of neuronal apoptosis compared with that in ACR alone. These results suggested that JNK contributed to ACR-induced apoptosis, while NF-κB acted as a protective regulator in response to ACR-induced neuropathy. This study helps to offer a deeper insight into the mechanism of ACR-induced neuropathy. K E Y W O R D S acrylamide, apoptosis, inflammation, mitogen-activated protein kinases, nuclear factor kappa B J Cell Biochem. 2019;120:3898-3910. wileyonlinelibrary.com/journal/jcb 3898 |

The Effect of Taxifolin on Acrylamide-induced Oxidative and Proinflammatory Brain Injury in Rats: A Biochemical and Histopathological Study

“…As seen in previous studies, acrylamide exposure induces an inflammatory response by the release of various cytokines. [6][7][8]17,27,33 In the present study, the TNF-α and IL-1β levels were found high in rat brains exposed to acrylamide. The same cytokines were found to be high in the acrylamide-treated rat brains in a study by Goudarzi et al 9 This suggests that inflammation may play a role in the development of acrylamide-induced brain damage.…”

“…neuron loss. 17 In the in vitro study of Park et al a high dose of 50 mg/kg was shown to trigger the death of neural progenitor cells and to impair adult hippocampal neurogenesis by increased intracellular ROS levels. 18 Acrylamide directly targets nerve terminals causing synaptic dysfunction via neurotransmitter release impairment.…”

“…One of the factors taking part in the development of the toxic effect of acrylamide is oxidative stress, 29 which results from an imbalance in the oxidative/antioxidative system and can lead to neuron death, as well as neuronal dysfunction. 30 In animal studies, acrylamide has been shown to increase oxidative damage markers in the brain and serum such as MDA, [6][7][8][9]17,21,22 8-hydroxydeoxyguanosine (8-OHdG), [6][7][8]27 TBA index 16 and nitric oxide, [6][7][8][9] indicating intracerebral lipid peroxidation.…”

“…Other papers also support this finding. In several studies, the rat brain tissue exposed to acrylamide exhibited a decrease in the levels of reduced glutathione (GSH) [6][7][8][9]16,17,21,22,31 and enzymatic antioxidants, such as superoxide dismutase, (6-9, 16) catalase,(6-9, 16) glutathione peroxidase, [6][7][8][9]21,31 glutathione S-transferase, 21 and glutathione reductase. 21 These data suggest that As in environmental exposures, the subchronic acrylamide treatment of mice at lower doses (max 200 µg/kg) did not significantly alter the numbers of newly generated cells in the hippocampus but affected their spatial learning and memory.…”

“…Yan et al found that acrylamide caused an increase in nuclear factor kappa B (NF-κB) activity in the brain tissue. 17 NF-κB is an oxidative stress-responsive transcription factor that activates the transcription of genes regulating the inflammatory and immune response. 32 This indicates a link between oxidative stress and inflammation.…”