Polystyrene microplastics-induced ROS overproduction disrupts the skeletal muscle regeneration by converting myoblasts into adipocytes.

The environmental problem of Microplastics (MPs) pollution poses a great threat to human and animal health, which has attracted global attention. The physiological integrity of skeletal muscle is extremely important for the survival of animals. Here, we investigated the effect of two size polystyrene microplastics (PS-MPs, 1-10 µm and 50-100 µm) on the growth of anterior tibial (TA) muscle and repair after injury in mice. Results showed that the regeneration of skeletal muscle was delayed by PS-MPs exposure and was negatively correlated with particle size. H&E staining and Oil red O staining showed that PS-MPs exposure reduced the average cross-sectional area (CSA) and diameter of the muscle fibers, increased lipid deposition. Further mechanistic research displayed that though PS-MPs treatment did not affect cell viability of myoblast, it aggravated intracellular ROS generation and oxidative stress, inhibited myogenic differentiation by decreasing the phosphorylation of p38 MAPK, and promote adipogenic differentiation by increasing the expression of NF-κB, which could be alleviated by NAC. In brief, our data demonstrated that the ROS overproduction caused by PS-MPs disturbed the regeneration of skeletal muscle and directed the fate of satellite cells in mice.

Methionine selenium antagonizes LPS-induced necroptosis in the chicken liver via the miR-155/TRAF3/MAPK axis.

Organic selenium has antioxidation and disease treatment effects. To explore the mechanisms of how methionine selenium alleviates necroptosis in the liver and whether this process is related to microRNA (miRNA) and the mitogen-activated protein kinase (MAPK) pathway, an animal model of methionine selenium and the lipopolysaccharide (LPS) interaction was established. The morphology, inflammatory factor (tumor necrosis factor-α [TNF-α]), necroptosis-related genes (RIP1, RIP3, MLKL, and caspase 8), MAPK pathway-related genes (JNK, ERK, and p38, p-JNK, p-ERK, and p-p38), gga-miR-155, TRAF3 (predicted target of gga-miR-155), and oxidative stress-related indicators (SOD, MDA, CAT, GSH, and GSH-Px) were analyzed from the perspective of the miR-155/TRAF3/MAPK axis to elucidate the mechanism of methionine selenium on the LPS-induced necroptosis mechanism in the chicken liver. The current results suggested that methionine selenium antagonizes oxidative stress, inflammation, and the MAPK pathway, thereby antagonizing the occurrence of necroptosis through multiple mechanisms. At the same time, methionine selenium affects miR-155/TRAF3/MAPK signaling, reduces miR-155 expression, and upregulates TRAF3 expression to inhibit necroptosis. This information provided new ideas and a theoretical basis for the practical application of methionine selenium, and it also enriched the study of miRNAs in birds and provided a reference for comparative medicine.

The antagonistic effect of selenium on lead-induced necroptosis via MAPK/NF-κB pathway and HSPs activation in the chicken spleen.

Recent studies identified a novel programmed and regulated cell death that was characterized by a necrotic cell death morphology, termed necroptosis. Lead (Pb) is known as a persistent inorganic environmental pollutant that affects the health of humans and animals worldwide. However, there are no detailed reports of Pb-induced necroptosis of immune tissue. Selenium (Se) is a trace element that antagonizes the toxicity of heavy metals. Here, chickens were randomly divided into four groups, treated with Pb ((CH3OO)2Pb, 150 mg/kg) and/or Se (Na2SeO3, 2 mg/kg), aim to study the effect and mechanism of necroptosis in Pb-induced spleen injury and the antagonistic effects of Se on Pb toxicity. Our results showed that Pb exposure evidently increased the accumulation of Pb in spleen and caused necroptosis by upregulating the expression of RIP1, RIP3 and MLKL, and decreasing Caspase8 expression. Meanwhile, Pb treatment inhibited the activities of SOD, GPX, and CAT, caused the accumulation of NO and MDA, and induced oxidative stress, which promoted the expression of MAPK/NF-κB pathway genes (ERK, JNK, P38, NF-κB and TNF-α) and activated HSPs (HSP27, HSP40, HSP60, HSP70 and HSP90). However, the increased content of Pb in spleen and Pb-caused necroptosis were inhibited by Se cotreatment. Overall, we conclude that Se can prevent Pb-induced necroptosis by restoring antioxidant functions and blocking the MAPK/NF-κB pathway and HSPs activation in chicken spleen.

DEHP induces neutrophil extracellular traps formation and apoptosis in carp isolated from carp blood via promotion of ROS burst and autophagy.

Di (2-ethylhexyl) phthalate (DEHP), a widely spreading environmental endocrine disruptor, has been confirmed to adversely affect the development of animals and humans. The formation of neutrophil extracellular traps (NETs) termed NETosis, is a recently identified antimicrobial mechanism for neutrophils. Though previous researches have investigated inescapable role of the immunotoxicity in DEHP-exposed model, relatively little is known about the effect of DEHP on NETs. In this study, carp peripheral blood neutrophils were treated with 40 and 200 µmol/L DEHP to investigate the underlying mechanisms of DEHP-induced NETs formation. Through the morphological observation of NETs and quantitative analysis of extracellular DNA, we found that DEHP exposure induced NETs formation. Moreover, our results proved that DEHP could increase reactive oxygen species (ROS) levels, decrease the expression of the anti-autophagy factor (mTOR) and the anti-apoptosis gene Bcl-2, and increase the expression of pro-autophagy genes (Dynein, Beclin-1 and LC3B) and the pro-apoptosis factors (BAX, Fas, FasL, Caspase3, Caspase8, and Caspase9), thus promoting autophagy and apoptosis. These results indicate that DEHP-induced ROS burst stimulates NETs formation mediated by autophagy and increases apoptosis in carp neutrophils.

Cadmium exposure induces apoptosis, inflammation and immunosuppression through CYPs activation and antioxidant dysfunction in common carp neutrophils.

Cadmium (Cd) is a bioaccumulative toxic heavy metal element that has been shown to cause irreversible damage to the immune system once contaminated with water, thereby jeopardizing the health of fish and other aquatic organisms. Neutrophils react against multiple invading pathogens through different mechanisms. The effect of Cd immunotoxicity in carp neutrophils has not been thoroughly studied. Here, common carp peripheral blood neutrophils were exposed to 10 µmol/L Cd for 2 h or then stimulated with 20 nmol/L PMA under laboratory conditions to study the effect and potential mechanism of Cd on neutrophils. The results showed that Cd induced mRNA expression of Cytochrome P450s (CYPs) enzymes including CYP1A1, CYP1B1, CYP1C and CYP3A138, increased reactive oxygen species (ROS) levels, and enhanced the expression of antioxidant genes. In addition, Cd activated cysteinyl aspartate specific proteinases (caspase-3) and induced apoptosis by altering the expression of major genes including mitochondrial pathway factors such as B-cell lymphoma-2 (Bcl-2), pro-apoptosis factors Bcl-2-Associated X (BAX), and caspase-9 and death receptor pathways such as Fas/Fas ligand (Fas/FasL), tumour necrosis factor alpha/tumor necrosis factor receptor 1 (TNF-α/TNFR1) and caspase-8. Meanwhile, we found that the accumulation of ROS caused not only oxidative stress but also high expression levels of related inflammatory factors to mediate the immune response including interleukin (IL-6, IL-10, IL-11b, IL-1ß) and interferon (IFNg1, IFNph1). Furthermore, Cd also inhibited phorbol myristate acetate (PMA)-induced release of neutrophil extracellular traps (NETs) and respiratory burst. This information will be helpful for the elucidation of how Cd impacts the neutrophils of carp. The associated risk assessment is valuable for effective aquatic environmental management.