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Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer that can damage various organizations and physiques through oxidative stress. Quercetin (Que) is a rich polyphenol flavonoid with good anti-inflammatory and antioxidant effects. However, the protection mechanism of Que against DEHP exposure-induced IPEC-J2 cell injury and the implication of autophagy, apoptosis and immunity are still unclear. In this experiment, we looked into the toxicity regime of DEHP exposure on IPEC-J2 cells and the antagonistic function of Que on DEHP. In the experiment, 135 μM DEHP and/or 80 μM Que were used to treat the IPEC-J2 cells for 24h. Experiments indicated that DEHP exposure can cause increased reactive oxygen species (ROS) levels leading to oxidative stress, decreased CAT, T-AOC and GSH-Px activities, increased MDA and H 2 O 2 accumulation, activated the ASK1/JNK signalling pathway, and further increases in the levels of apoptosis markers Bax, Caspase3, Caspase9, and Cyt-c, while reduced the Bcl-2 expression. DEHP also increased the expression of genes linked to autophagy (ATG5, Beclin1, LC3), while decreasing the expression of P62. Additionally, DEHP exposure led to elevated levels of IL1-β, IL-6, MCP-1, and TNF expression. When exposed to Que alone, there were no significant changes in cellular oxidative stress level, ASK1/JNK signalling pathway expression level, apoptosis, autophagy and cellular immune function. The combination of DEHP and Que treatment remarkably decreased the proportion of autophagy and apoptosis, and recovered cellular immunity. In summary, Que can attenuate DEHP-induced apoptosis and autophagy in IPEC-J2 cells by regulating the ROS/ASK1/JNK signalling pathway and improving the immune dysfunction of IPEC-J2 cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Trimethyltin chloride (TMT) is an organotin-based contaminant present in the water environment that poses a great threat to aquatic organisms and humans. The liver is the detoxification organ of the body and TMT exposure accumulates in the liver. Tea polyphenol (TP) is a natural antioxidant extracted from tea leaves and has been widely used as a food and feed additive. To investigate the mechanism of toxicity caused by TMT exposure on grass carp hepatocytes (L8824 cells) and the mitigating effect of TP, we established a hepatocyte model of TMT toxicity and/or TP treatment. L8824 cells were treated with 0.5 μM of TMT and/or 4 μg/mL of TP for 24 h and assayed for relevant indices. The results showed that TMT exposure caused oxidative stress, resulting in increased intracellular ROS content, resulting in intracellular ROS accumulation and increased MDA content, and inhibiting the activities of T-AOC, SOD, CAT, and GSH. Meanwhile, TMT exposure activated the endoplasmic reticulum apoptotic signaling pathway, resulting in abnormal expression of GRP78, ATF-6, IRE1, PERK, Caspase-3 and Caspase-12. In addition, TMT exposure also led to up-regulation of cytokines IL-1β, IL-6, TNF-α, and decreased expression of IL-2, IFN-γ, and antimicrobial peptides Hepcidin, β-defensin, and LEAP2. However, the addition of TP could mitigate the above changes. In conclusion, TP can alleviate TMT exposure-mediated hepatotoxicity by inhibiting ROS/ER stress in L8824 cells. In addition, this trial enriches the cytotoxicity study of TMT and provides a new theoretical basis for the use of TP as a mitigating agent for TMT., Competing Interests: Conflict of interest Author declares no conflict of interest., (Copyright © 2022. Published by Elsevier Inc.)

Di (2-ethylhexyl) phthalate (DEHP) is often used as a plasticizer for plastic products, and its excessive use can cause irreversible damage to aquatic animals and humans. Evodiamine (EVO) is an alkaloid component in the fruit of Evodia rutaecarpa, which has antioxidant and detoxification functions. To investigate the toxic mechanism of DEHP on grass carp (Ctenopharyngodon idellus) hepatocyte cell line (L8824) and the therapeutic effect of evodiamine, an experimental model of L8824 cells exposed to 800 μM DEHP and/or 10 μM EVO for 24 h was established. Flow cytometry, AO/EB fluorescence staining, real-time quantitative PCR, and western blot were used to detect the degree of cell injury, oxidative stress level, MAPK signaling pathway relative genes, and the expression of apoptosis-related molecules. The results showed that DEHP exposure could significantly increase the level of reactive oxygen species (ROS), inhibit the activities of antioxidant enzymes (CAT, SOD, GSH-Px), and cause the accumulation of MDA. DEHP also activated MAPK signaling pathway-related molecules (JNK, ERK, P38 MAPK), and then up-regulated the expression of pro-apoptotic factors Bcl-2-Associated X (Bax) and caspase 3, while inhibiting the anti-apoptotic factor B-cell lymphoma-2 (Bcl-2). In addition, EVO can also promote the dissociation of nuclear factor-E2-related factor 2 (Nrf2) into the nucleus, reduce the level of ROS and the occurrence of oxidative stress in grass carp hepatocytes, down-regulate the MAPK pathway, alleviate DEHP-induced apoptosis, and restore the expression of antioxidant genes. These results indicated that evodiamine could block Nrf2/MAPK pathway to inhibit DEHP-induced apoptosis of grass carp hepatocytes., Competing Interests: Declaration of competing interest The authors state that they have no known competitive economic interests or personal relationships that may affect the work reported in this article., (Copyright © 2022 Elsevier Inc. All rights reserved.)