Combined Toxicity of Xenobiotics Bisphenol A and Heavy Metals on Zebrafish Embryos (Danio rerio)

Environmental pollutants may cause adverse effects on the immune system of aquatic organisms. This study revealed that combination of environmental pollutants and Bisphenol A(BPA) could cause an acute inflammatory response in zebrafish larvae as shown by body alterations, which may imply a common immunotoxicity mechanism for most environmental pollutants. In the present study we evaluated the toxicity after co-exposure of BPA and Cd or Cr (III) in zebrafish embryos and larvae, and the oxidative stress pathway involved. Evaluation of lethal and developmental endpoints such as hatching, edema, malformations, abnormal heart rate and survival rate were evaluated after 96 h of exposure. Combination of BPA at 10 μM with Cd or Cr at 0.5 μM exposure induce malformations at 96 hpf in zebrafish larvae, as well as significantly increases oxidative stress and induce apoptosis on larvae. Our study suggested how environmental pollutant showed a synergistic effect at common not-effective doses, promoting decrease of antioxidant defense and contrasted fish development.

The Parental Pesticide and Offspring’s Epigenome Study: Towards an Integrated Use of Human Biomonitoring of Exposure and Effect Biomarkers

In Morocco, due to the lack of education and the presence of a counterfeit market, pesticides constitute a major problem to be addressed by occupational and environmental health agencies. This paper aims to introduce the PaPOE (Parental Pesticides and Offspring Epigenome) prospective study and its goals, to motivate the study rationale and design, and to examine comprehensively whether multi-residue exposure to commonly used pesticides could induce epigenetic alterations through the oxidative stress pathway. The PaPOE project includes a cross-sectional study assessing the occupational exposure among 300 farmworkers in Meknes, and initiates a birth cohort of 1000 pregnant women. Data and biological samples are collected among farmworkers, and throughout pregnancy, and at birth. Oxidative stress biomarkers include Glutathione, Malondialdehyde, and 8-OHdG. Global and gene-specific DNA methylation is assessed. The study began enrollment in 2019 and is ongoing. As of 30 June 2021, 300 farmworkers and 125 pregnant women have enrolled. The results are expected to showcase the importance of biomonitoring for understanding individual risks, and to identify a number of regions where DNA methylation status is altered in the pesticides-exposed population, paving the way for an integrated biomonitoring system in Morocco and Africa to assess environmental exposures and their long-term health consequences.

Aflatoxin B1 Toxicity in Zebrafish Larva (Danio rerio): Protective Role of Hericium erinaceus

Aflatoxin B1 (AFB1), a secondary metabolite produced by fungi of the genus Aspergillus, has been found among various foods as well as in fish feed. However, the effects of AFB1 on fish development and its associated toxic mechanism are still unclear. In the present study, we confirmed the morphological alterations in zebrafish embryos and larvae after exposure to different AFB1 doses as well as the oxidative stress pathway that is involved. Furthermore, we evaluated the potentially protective effect of Hericium erinaceus extract, one of the most characterized fungal extracts, with a focus on the nervous system. Treating the embryos 6 h post fertilization (hpf) with AFB1 at 50 and 100 ng/mL significantly increased oxidative stress and induced malformations in six-day post-fertilization (dpf) zebrafish larvae. The evaluation of lethal and developmental endpoints such as hatching, edema, malformations, abnormal heart rate, and survival rate were evaluated after 96 h of exposure. Hericium inhibited the morphological alterations of the larvae as well as the increase in oxidative stress and lipid peroxidation. In conclusion: our study suggests that a natural extract such as Hericium may play a partial role in promoting antioxidant defense systems and may contrast lipid peroxidation in fish development by counteracting the AFB1 toxicity mechanism.

Maresin 1 Attenuates Ventilator-induced Lung Injury by Reducing Oxidative Stress through the Nrf2/HO-1 and NF-κB Pathways

Mechanical ventilation could support the lives of patients with respiratory failure in a variety of ways, including maintaining airway patency and improving oxygenation, etc. However, mechanical ventilation itself could lead to lung damage, which is called mechanical ventilation-related lung injury (VILI). The incidence of VILI is high and the prognosis is poor, so clarifying the mechanism of VILI and seeking effective preventive and therapeutic measures are the urgent medical problem to be resolved. By constructing the VILI model, we studied the effect of Maresin1 on VILI and explored its possible mechanism at the animal level. We tested the related indicators of lung injury, the oxidative stress response, and the inflammatory response. The results indicated that Maresin1 could inhibit the oxidative stress response and excessive inflammation, thus ameliorating lung injury in VILI. We also detected the expression levels of the principal oxidative stress pathway Nrf2 / HO-1 and the key inflammatory transcription factor NF-κB. We used the HO-1 inhibitor ZnPP to further confirm our conclusion. Our results suggested for the first time that Maresin1 could promote the activation of the Nrf2 / HO-1 pathway and significantly suppress the expression of NF-κB to exert a positive role in VILI.

EZH2 Alleviates Antituberculosis Drug-Induced Liver Injury in Mice by Reducing H3K27 Trimethylation at the Nrf2 Promoter

BackgroundAnti-tuberculosis drug-induced liver injury (ADLI) limits the treatment of tuberculosis. The mechanisms underlying ADLI are unclear and there are no effective preventative measures to avoid this complication. MethodsIn this stuy, the protein contents of EZH2, Nrf2, NQO1 and HO-1 were detected by ELISA kit, while those of EZH2 and Nrf2 were determined by Western blot. The Chip experiment was used to detect the level of H3K27me3 in the Nrf2 promoter region.The liver were analyzed histopathologically in vivo using hematoxylin and eosin staining.ResultsHere we developed a murine model of ADLI that recapitulates liver injury in the human disease. Using this model, we investigated the potential involvement of the enhancer of zeste homolog 2 methyltransferase (EZH2), a histone methyltransferase which inhibits the transcriptional activation of the Nrf2-ARE oxidative stress pathway. Compared to controls, mice livers with ADLI showed decreased expression of EZH2 together with reduced H3K27me3 marks in the Nrf2 promoter. This was accompanied by increased expression of Nrf2 and its target genes NQO1 and HO-1. Liver injury in the mice with ADLI could be alleviated to an extent by in vivo delivery of siRNAs targeting EZH2, which further downregulated EZH2 expression and H3K27me3 levels in the Nrf2 promoter along with accompanying increases in Nrf2, NQO1 and HO-1 expression. ConclusionsTherefore, inhibiting EZH2 likely reduced liver damage in ADLI by enhancing this key anti-oxidative stress pathway. Our results establish a role for EZH2 in a mouse model of ADLI and furthermore provides valuable mechanistic insights into the development of ADLI pathology.