Allicin Ameliorates Intestinal Barrier Damage via Microbiota-Regulated Short-Chain Fatty Acids-TLR4/MyD88/NF-κB Cascade Response in Acrylamide-Induced Rats.

Acrylamide (AA) is a heat-induced toxicant, which can cause severe damage to health. In the present study, SD rats were used to investigate the potential therapeutic effects of allicin dietary supplementation in the rats with AA-induced intestinal injury. The elevated expression of occludin, claudin-1, zonula occludens-1 (ZO-1), mucin 2, and mucin 3 indicated that oral allicin alleviated the intestinal epithelial barrier breakage induced by AA, compared with the AA-treated group. In the gut microbiota, Bacteroides, Escherichia_Shigella, Dubosiella, and Alloprevotella related to the synthesis of short-chain fatty acids (SCFAs) were negatively affected by AA, while allicin regulated cascade response of the microbiota-SCFAs signaling to reverse the reduction of acetic acid and propionic acid by AA treatment. Allicin also dramatically down-regulated the expression of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), NF-κB signaling pathway proteins, and proinflammatory cytokines by promoting the production of SCFAs in AA-treated rats. Allicin relieved the intestinal barrier injury and inflammation caused by AA as evidenced by the regulation cascade response of the microbiota-SCFAs-TLR4/MyD88/NF-κB signaling pathway. In conclusion, allicin is highly effective in the treatment and prevention of AA-induced intestinal injury.

Rosmarinic acid attenuates acrylamide induced apoptosis of BRL-3A cells by inhibiting oxidative stress and endoplasmic reticulum stress.

Acrylamide (AA) is a common endogenous contaminant in food, with a complex toxicity mechanism. The study on liver damage to experimental animals caused by AA has aroused a great attention. Rosmarinic acid (RosA) as a natural antioxidant shows excellent protective effects against AA-induced hepatotoxicity, but the potential mechanism is still unclear. In the current study, the protective effect of RosA on BRL-3A cell damage induced by AA was explored. RosA increased the activity of SOD and GSH, reduced the content of ROS and MDA, and significantly reduced the oxidative stress (OS) damage of BRL-3A cells induced by AA. RosA pretreatment inhibited the MAPK signaling pathway activated by AA, and down-regulated the phosphorylation of JNK, ERK and p38. RosA pretreatment also reduced the production of calcium ions caused by AA. In addition, the key proteins p-IRE1α, XBP-1s, TRAF2 of the IRE1 pathway, and the expression of endoplasmic reticulum stress (ERS) characteristic proteins GRP78, p-ASK1, Caspase-12 and CHOP were also down-regulated by RosA. NAC blocked the activation of the MAPK signaling pathway and inhibited the ERS pathway. RosA reduced the rate of apoptosis and down-regulated the expression of Bax/Bcl-2 and Caspase-3, thereby inhibiting AA-induced apoptosis. In conclusion, RosA reduced the OS and ERS induced by AA in BRL-3A cells, thereby inhibiting cell apoptosis, and it could be used as a potential protective agent against AA toxicity.

Acrylamide induces NLRP3 inflammasome activation via oxidative stress- and endoplasmic reticulum stress-mediated MAPK pathway in HepG2 cells.

Acrylamide (AA) is one of the important products of the Maillard reaction. AA hepatotoxicity is related to inflammation, which can be indicated by the activation of NLRP3 inflammasome. In this study, AA activated NLRP3 inflammasome and released a large number of inflammatory factors in HepG2 cells. AA induced oxidative stress (OS) and endoplasmic reticulum stress (ERS) responses in HepG2 cells, accompanied by the activation of the MAPK signaling pathway. When HepG2 cells were pretreated with ROS (NAC) and ERS (4-PBA) inhibitors separately, the activation of NLRP3 inflammasome was inhibited. The MAPK signaling pathway was inhibited when OS and ERS were blocked. HepG2 cells pretreated with MAPK selective inhibitors led to the inhibition on the activation of NLRP3 inflammasome. Overall, we consider that AA induces the activation of NLRP3 inflammasome through the OS- and ERS-mediated MAPK signaling pathway in HepG2 cells.