Hematopoiesis is a complex and intricate process that aims to replenish blood components in a constant fashion. It is orchestrated mostly by hematopoietic progenitor cells (hematopoietic stem cells (HSCs)) that are capable of self-renewal and differentiation. These cells can originate other cell subtypes that are responsible for maintaining vital functions, mediate innate and adaptive immune responses, provide tissues with oxygen, and control coagulation. Hematopoiesis in adults takes place in the bone marrow, which is endowed with an extensive vasculature conferring an intense flow of cells. A myriad of cell subtypes can be found in the bone marrow at different levels of activation, being also under constant action of an extensive amount of diverse chemical mediators and enzymatic systems. Bone marrow platelets, mature erythrocytes and leukocytes are delivered into the bloodstream readily available to meet body demands. Leukocytes circulate and reach different tissues, returning or not returning to the bloodstream. Senescent leukocytes, specially granulocytes, return to the bone marrow to be phagocytized by macrophages, restarting granulopoiesis. The constant high production and delivery of cells into the bloodstream, alongside the fact that blood cells can also circulate between tissues, makes the hematopoietic system a prime target for toxic agents to act upon, making the understanding of the bone marrow microenvironment vital for both toxicological sciences and risk assessment. Environmental and occupational pollutants, therapeutic molecules, drugs of abuse, and even nutritional status can directly affect progenitor cells at their differentiation and maturation stages, altering behavior and function of blood compounds and resulting in impaired immune responses, anemias, leukemias, and blood coagulation disturbances. This review aims to describe the most recently investigated molecular and cellular toxicity mechanisms of current major environmental pollutants on hematopoiesis in the bone marrow.

Mitochondria play a crucial role in cellular respiration, ATP production, and the regulation of various cellular processes. Mitochondrial dysfunctions have been directly linked to pathophysiological conditions, making them a significant target of interest in toxicological research. In recent years, there has been a growing need to understand the intricate effects of xenobiotics on human health, necessitating the use of effective scientific research tools. Caenorhabditis elegans (C. elegans), a nonpathogenic nematode, has emerged as a powerful tool for investigating toxic mechanisms and mitochondrial dysfunction. With remarkable genetic homology to mammals, C. elegans has been used in studies to elucidate the impact of contaminants and drugs on mitochondrial function. This review focuses on the effects of several toxic metals and metalloids, drugs of abuse and pesticides on mitochondria, highlighting the utility of C. elegans as a model organism to investigate mitochondrial dysfunction induced by xenobiotics. Mitochondrial structure, function, and dynamics are discussed, emphasizing their essential role in cellular viability and the regulation of processes such as autophagy, apoptosis, and calcium homeostasis. Additionally, specific toxins and toxicants, such as arsenic, cadmium, and manganese are examined in the context of their impact on mitochondrial function and the utility of C. elegans in elucidating the underlying mechanisms. Furthermore, we demonstrate the utilization of C. elegans as an experimental model providing a promising platform for investigating the intricate relationships between xenobiotics and mitochondrial dysfunction. This knowledge could contribute to the development of strategies to mitigate the adverse effects of contaminants and drugs of abuse, ultimately enhancing our understanding of these complex processes and promoting human health.

Overnutrition and the consumption of Western-type diets lead to chronic low-grade systemic inflammation (ie metainflammation) and a dysfunctional immune response. Although neutrophils are affected by metainflammation, mechanistic evidence regarding the direct effects of dietary fat exposure on neutrophil function and migration in vivo, particularly in response to injury, remains limited. Here, we investigated how metainflammation induced by a high-cholesterol diet (HCD) influences neutrophil function and migration following tissue injury. We employed a tailfin transection model in juvenile zebrafish larvae with fluorescently tagged neutrophils fed an HCD and assessed neutrophil function and migration dynamics in vivo at the injury site and whole animal. We combined long-term, noninvasive intravital confocal microscopy with computational analysis to examine neutrophil behavior, and photoconversion techniques to track neutrophil mobilization across the larvae. Exposure to HCD resulted in a dysfunctional neutrophil response characterized by exacerbated recruitment, increased reactive oxygen species production and NETosis, impaired apoptosis, and delayed inflammation resolution. Neutrophil forward and reverse migration were also significantly impacted at the injury site. Moreover, we identified diet-inflamed regions such as the liver and intestine as sources of activated neutrophils that reverse migrate and respond to injuries at distant sites, contributing to interorgan transmission of inflammation. Finally, ameliorating steatosis and systemic chronic inflammation rescued the exaggerated neutrophil recruitment to injury. Overall, our study highlights the crucial role of neutrophil dysregulation and reverse migration from diet-induced inflamed tissues in driving exacerbated and dysfunctional inflammatory responses to injury, providing insight into potential therapeutic strategies to alleviate these effects in metabolic disease context.