Evaluation of genotoxic damage, production reactive oxygen and nitrogen species in Plasmodium yoelii yoelii exposed to sodium metavanadate.

Malaria represents the greatest global health burden among all parasitic diseases, with drug resistance representing the primary obstacle to control efforts. Sodium metavanadate (NaVO3) exhibits antimalarial activity against the Plasmodium yoelii yoelii (Pyy), yet its precise antimalarial mechanism remains elusive. This study aimed to assess the antimalarial potential of NaVO3, evaluate its genotoxicity, and determine the production of reactive oxygen and nitrogen species (ROS/RNS) in Pyy. CD-1 mice were infected and divided into two groups: one treated orally with NaVO3 (10 mg/kg/day for 4 days) and the other untreated. A 50% decrease in parasitemia was observed in treated mice. All experimental days demonstrated DNA damage in exposed parasites, along with an increase in ROS and RNS on the fifth day, suggesting a possible parasitostatic effect. The results indicate that DNA is a target of NaVO3, but further studies are necessary to fully elucidate the mechanisms underlying its antimalarial activity.

The multiple facets of the club cell in the pulmonary epithelium.

The non-ciliated bronchiolar cell, also referred to as "club cell", serves as a significant multifunctional component of the airway epithelium. While the club cell is a prominent epithelial type found in rodents, it is restricted to the bronchioles in humans. Despite these differences, the club cell's importance remains undisputed in both species due to its multifunctionality as a regulatory cell in lung inflammation and a stem cell in lung epithelial regeneration. The objective of this review is to examine different aspects of club cell morphology and physiology in the lung epithelium, under both normal and pathological conditions, to provide a comprehensive understanding of its importance in the respiratory system.

El endotelio sano y su disfunción en el riesgo cardiovascular / Healthy Endothelium and its Dysfunction in Cardiovascular Risk

Resumen El endotelio es una monocapa formada por células aplanadas llamadas w, que revisten la parte más interna del corazón, los vasos sanguíneos y los linfáticos. Es considerado un órgano que tiene una función de barrera, pero además se encarga de regular la permeabilidad y tono vascular, hemostasia, inflamación y angiogénesis. Esta revisión se centra sobre todo en las generalidades del endotelio vascular sano y su disfunción. Se analizan los conceptos de activación y disfunción, en donde la activación se considera como un proceso autolimitado, indispensable para la hemostasia y la inflamación. La disfunción endotelial, en cambio, es un proceso patológico, de mayor duración y que se presenta cuando el endotelio ya no puede autorregularse y cambia a un fenotipo proinflamatorio y protrombótico permanente. Esta disfunción es el primer cambio que lleva a la ateroesclerosis y al aumento del riesgo cardiovascular, por esta razón se revisan los principales biomarcadores de disfunción endotelial y riesgo cardiovascular. A medida que se avance en el conocimiento básico del endotelio y su disfunción, será posible diseñar nuevas medidas preventivas o terapéuticas que puedan disminuir dicho riesgo.

Abstract The endothelium is a monolayer of flatten cells named endothelial cells that form the inner layer of the heart, blood, and lymphatic vessels. Its function is not just as a barrier, but it is a regulator of vascular permeability and tone, hemostasis, inflammation, and angiogenesis. This review is about the general aspects of vascular endothelium and endothelial dysfunction that leads to increased vascular risk. Activation and dysfunction are discussed, considering the endothelial activation as a self-limiting process, necessary to promote inflammation and hemostasis. Endothelial dysfunction is a pathological process in which the endothelium loses its ability for self-regulation and acquires a prothrombotic and proinflammation phenotype. Endothelial dysfunction is the initial step for atherosclerosis and increased cardiovascular risk, so the main biomarkers of endothelial dysfunction are reviewed. As basic knowledge about endothelium increases, preventive or therapeutic measures can be designed as treatment or prevention the risk of its dysfunction.

Sex differences in vanadium inhalation effects in non-ciliated bronchiolar cells.

The non-ciliated bronchiolar cell (NCBC) is responsible for the defense of the lung and responds to negative stimuli such as exposure to toxic pro-oxidant substances, which triggers the hyperproduction and hypersecretion of mucins and CC16 protein. The literature demonstrates that physiological and pathological responses in the lung can be influenced by the organism's sex. The objective of this report was to evaluate response differences to vanadium (V) inhalation in male and female CD-1 mice. Mice were exposed to V for four weeks. Hyperplasia of bronchiolar epithelium, small inflammatory foci and sloughing of the NCBC were observed, without changes between sexes and throughout the exposure time. Mucosecretory metaplasia was found in both males and females, however it was more drastic in males. The expression of CC16 increased in both sexes. This study demonstrated a different susceptibility between male and female mice exposed to V inhalation regarding mucosecretory metaplasia.

Toxic Effects of Inhaled Vanadium Attached to Particulate Matter: A Literature Review.

Environmental pollution is a worldwide problem recognized by the World Health Organization as a major health risk factor that affects low-, middle- and high-income countries. Suspended particulate matter is among the most dangerous pollutants, since it contains toxicologically relevant agents, such as metals, including vanadium. Vanadium is a transition metal that is emitted into the atmosphere especially by the burning of fossil fuels to which dwellers are exposed. The objective of this literature review is to describe the toxic effects of vanadium and its compounds when they enter the body by inhalation, based especially on the results of a murine experimental model that elucidates the systemic effects that vanadium has on living organisms. To achieve this goal, we reviewed 85 articles on the relevance of vanadium as a component of particulate matter and its toxic effects. Throughout several years of research with the murine experimental model, we have shown that this element generates adverse effects in all the systems evaluated, because it causes immunotoxicity, hematotoxicity, neurotoxicity, nephrotoxicity and reprotoxicity, among other noxious effects. The results with this experimental model add evidence of the effects generated by environmental pollutants and increase the body of evidence that can lead us to make more intelligent environmental decisions for the welfare of all living beings.

Effects of Vanadium Inhalation and Sweetened Beverage Ingestion in Mice: Morphological and Biochemical Changes in the Liver.

The aim of this report was to evaluate the morphological and biochemical changes in the liver by the inhalation of vanadium and consumption of sweetened beverages in a subchronic murine model. Forty CD-1 male mice were randomly divided into four groups: control, vanadium (V), sucrose 30% (S), and vanadium-sucrose (V + S). V was inhaled (1.4 mg/m3) for 1h, twice/week; 30% sucrose solution was given orally ad libitum. Blood samples were obtained for AST, ALT, and LDH determination. Liver samples were processed for histological and oxidative stress immunohistochemical evaluation with 4-hydroxynonenal at weeks 4 and 8 of exposure. Regarding liver function tests, a statistically significant increase (P < 0.05) was observed in groups V, S, and V + S at weeks 4 and 8 compared to the control group. A greater number of hepatocytes with meganuclei and binuclei were observed in V and V + S at week 8 compared to the other groups. Steatosis and regenerative changes were more extensive in the eighth week V + S group. 4-Hydroxynonenal immunoreactivity increased in the V + S group at both exposure times compared to the other groups; however, the increment was more evident in the V + S group at week 4 compared to the V + S group at week 8. An increase in De Ritis ratio (>1) was noticed in experimental groups at weeks 4 and 8. Findings demonstrate that in the liver, V, S, and V + S induced oxidative stress and regenerative changes that increased with the length of exposure. Results support possible potentiation of liver damage in areas with high air pollution and high-sweetened beverage consumption.

A brief review of the biology of megakaryocytes and platelets and their role in thrombosis associated with particulate air pollution.

Air pollution is a worldwide public health issue and it is associated with millions of premature deaths due to cancer, thrombosis, and pulmonary and cardiovascular diseases. Thrombosis is the excessive clotting that blocks a blood vessel, and its etiology is multifactorial. In recent years, growing evidence has linked air pollution, especially particulate matter (PM) and metals, to the development of thrombosis. PM and metals induce lung and systemic inflammation and oxidative stress that are frequent mechanisms in thrombosis. Platelets are important effectors of physiological hemostasis and pathological thrombosis. They are responsible for the formation of the initial plug and are important in the cellular model of coagulation. Therefore, any changes in their morphology or function or an increase in activation could be extremely relevant in thrombosis. Megakaryocytes (MKs) in the bone marrow and in the lungs are the precursor cells of platelets, and the latter is the first organ injured by air pollution. There is substantial evidence of the effect that PM and metals have on platelets, but there is almost no research about the effect of PM and metals on MKs. It is very likely that the alterations produced by air pollution originate in these cells. In this article, we review the biology of MKs and platelets and their role in particulate air pollution-related thrombosis to emphasize the need for further research in this field.

Fisiología de la hemostasia y su alteración por la coagulopatía en COVID-19 / Physiology of Hemostasis and its Alteration by Coagulopathy in COVID-19

Resumen La pandemia de la enfermedad COVID-19, ocasionada por el virus Sars-CoV-2, ha preocupado al personal de salud, entre otras cosas, por la alta incidencia de coagulopatía asociada a aumento en la mortalidad que se presenta en los pacientes. La coagulopatía es principalmente trombótica, inicialmente en pulmón y posteriormente sistémica, macro y microvascular, asociada al daño endotelial, inflamación, trampas extracelulares de neutrófilos (NETs), activación de macrófagos y tormenta de citocinas que perpetúan el círculo vicioso de trombosis e inflamación. Se ha reportado el aumento de factores protrombóticos en los pacientes: aumento del factor tisular, factor de Von Willebrand, fibrinógeno, factor VIII, entre otros y, además, la disminución de algunos anticoagulantes naturales como la proteína S y la antitrombina. Además, se menciona la insuficiencia de la fibrinólisis, asociada con el aumento del PAI-1 (inhibidor del activador tisular de plasminógeno). Durante la enfermedad, hay depósito de fibrina intraalveolar que también es degradada. Tanto la fibrinólisis del trombo, como la degradación de fibrina intraalveolar, hacen que aumenten los dímeros D y, por esta razón, este es uno de los mejores predictores de la severidad de la enfermedad COVID-19. En este artículo se revisa la fisiología de la hemostasia, la tromboinflamación secundaria a la infección por el virus Sars-Cov-2, la evidencia clínica y lo que se sabe de la fisiopatología de la coagulopatía en COVID-19, para tratar de entenderla desde la mirada de la ciencia básica.

Abstract COVID-19 global pandemic caused by Sars-CoV-2 virus, has worried to health care providers due to the high mortality rate related to coagulopathy in many patients. COVID-19 coagulopathy is mainly thrombotic, first locally in lungs but later on it becomes micro and macrovascular systemic coagulopathy. It has been associated to endothelial damage, inflammation, neutrophil-extracellular traps, monocyte and macrophage activation, cytokines storm that induce a vicious cycle of thrombosis and inflammation. The increased levels of prothrombotic factors as tissue factor, Von Willebrand factor, fibrinogen, VIII factor and the decreased levels of antithrombotic factos, such as: antithrombin and Protein S have been reported in COVID-19 patients. Insufficiency of fibrinolysis because of the increased levels of PAI-1 (plasminogen activator inhibitor 1) have been reported also. During this disease there are intraalveolar fibrin deposits that needs to be degraded. Fibrinolysis of thrombus and fibrin intraalveolar degradation are responsible for the high increase of D-dimers levels that are an important predictor of severity of the disease. In this report, the physiology of hemostasis, thromboinflamation secondary to Sars-CoV-2 infection are reviewed, as well as the clinical evidence and the physiopathology of COVID-19 coagulopathy from the basic sciences point of view.

The role of the non-ciliated bronchiolar cell in tolerance to inhaled vanadium of the bronchiolar epithelium.

The Non-Ciliated Bronchiolar Cell (NCBC) is responsible for the defense and maintenance of the bronchiolar epithelium. Several cellular defense mechanisms have been associated with an increase in the secretion of CC16 and changes in the phenotype of the cell; these mechanisms could be linked to tolerance to the damage due to exposure to inhaled Particulate Matter (PM) of the epithelium. These defense mechanisms have not been sufficiently explored. In this article, we studied the response of the NCBC to inhaled vanadium, an element which adheres to PM. This response was measured by the changes in the phenotype of the NCBC and the secretion of CC16 in a mouse model. Mice were exposed in two phases to different vanadium concentrations; 1.27 mg/m³ in the first phase and 2.56 mg/m³ in the second phase. Mice were sacrificed on the 2nd, 4th, 5th, 6th and 8th weeks. In the second phase, we observed the following: sloughing of the NCBC, hyperplasia and small inflammatory foci remained without changes and that the expression of CC16 was higher in this phase than in phase I. We also observed a change in the phenotype with a slow decrease in both phases. The increase in the secretion of CC16 and the phenotype reversion could be due to the anti-inflammatory activity of CC16. The changes observed in the second phase could be attributed to the tolerance to inhaled vanadium.

Changes in Ovarian and Uterine Morphology and Estrous Cycle in CD-1 Mice After Vanadium Inhalation.

Vanadium is a metal present in particulate matter and its reprotoxic effects have been demonstrated in males and pregnant females in animal models. However, the effects of this metal on the reproductive organs of nonpregnant females have not been sufficiently studied. In a vanadium inhalation model in nonpregnant female mice, we found anestrous and estrous cycle irregularity, as well as low serum concentrations of 17ß-estradiol and progesterone. A decrease in the diameter of secondary and preovulatory follicles, as well as a thickening of the myometrium and endometrial stroma, was observed in the vanadium-treated mice. There was no difference against the control group with respect to the presence of the estrogen receptor α in the uterus of the animals during the estrous stage. Our results indicate that when vanadium is administered by inhalation, effects are observed on the female reproductive organs and the production of female sex hormones.

El megacariocito: una célula muy original / The megakaryocyte: a very original cell

Resumen El megacariocito es la célula más grande de la médula ósea, por lo tanto es relativamente fácil reconocer su presencia al observar un aspirado o una biopsia de este tejido. Difiere de otras células por su tamaño, por ser poliploide y crecer por endomitosis. No hay otra célula humana que crezca así. Además, tiene funciones biológicas muy importantes. La más conocida es el dar origen a las plaquetas, que son indispensables para la hemostasia y la reparación de los vasos sanguíneos dañados, así como para la cicatrización de los tejidos que rodean a las heridas. Sin embargo, en los últimos años, a los megacariocitos también se les han atribuido algunas otras funciones que discutiremos en esta revisión.

Abstract The Megakaryocyte is the biggest cell in the bone marrow; therefore, it is easy to recognize in a bone marrow aspirate. In humans, this cell differs from others because of its size, its polyploidy and because it grows by endomitosis. It is the only human cell that grows this way. In addition, the megakaryocyte has very important biological functions. Its best-known function is being in charge of the production of platelets, which are essential for hemostasis, the repair of damaged blood vessels, and healing the tissues surrounding wounds. However, in recent years, other functions have been attributed to the megakaryocyte, which will be discussed in this review.

Neuroprotective effect of carnosine in the olfactory bulb after vanadium inhalation in a mouse model.

Carnosine (ß-alanyl-L-histidine) is synthesized in the olfactory system, has antioxidant activity as a scavenger of free radicals and has been reported to have neuroprotective action in diseases which have been attributed to oxidative damage. In neurodegenerative disorders, such as Parkinson's and Alzheimer's diseases, impairment of olfactory function has been described. Vanadium derivatives are environmental pollutants, and its toxicity has been associated with oxidative stress. Vanadium toxicity on the olfactory bulb was reported previously. This study investigates the neuroprotective effect of carnosine on the olfactory bulb in a mice model of vanadium inhalation. Male mice were divided into four groups: vanadium pentoxide (V2 O5 ) [0.02 mol/L] inhalation for one hour twice a week; V2 O5 inhalation plus 1 mg/kg of carnosine administered daily; carnosine only, and the control group that inhaled saline. The olfactory function was evaluated using the odorant test. Animals were sacrificed four weeks after exposure. The olfactory bulbs were dissected and processed using the rapid Golgi method; cytological and ultrastructural analysis was performed and malondialdehyde (MDA) concentrations were measured. The results showed evidence of olfactory dysfunction caused by vanadium exposure and also an increase in MDA levels, loss of dendritic spines and necrotic neuronal death in the granule cells. But, in contrast, vanadium-exposed mice treated with carnosine showed an increase in dendritic spines and a decrease in neuronal death and in MDA levels when compared with the group exposed to vanadium without carnosine. These results suggest that dendritic spine loss and ultrastructural alterations in the granule cells induced by vanadium are mediated by oxidative stress and that carnosine may modulate the neurotoxic vanadium action, improving the olfactory function.

Estilo de vida, contaminación atmosférica y problemas que afectan la salud reproductiva en la mujer / Life style, atmospheric pollution and reproductive issues affecting women´s health Abstract

Resumen A nivel mundial, la infertilidad en las parejas ha ido en aumento. Hay muchas causas implicadas en este problema, sin embargo, un factor que influye y que cada vez cobra mayor presencia e importancia es la contaminación atmosférica. Aunque tanto las mujeres como los hombres pueden presentar alteraciones que les impidan ser fértiles, en esta revisión se describen 2 factores que han demostrado afectar la salud reproductiva femenina: el estilo de vida y la contaminación ambiental. Entre los factores de estilo de vida que afectan a la salud reproductiva en las mujeres se incluyen el tabaquismo, la obesidad, el estrés y el aplazamiento de la maternidad. Por el lado de la contaminación atmosférica, se ha demostrado que los plaguicidas organoclorinados, los derivados de combustibles fósiles, los hidrocarburos aromáticos policíclicos, los óxidos de azufre y de nitrógeno, los metales y las partículas suspendidas, generan efectos adversos sobre la capacidad de embarazarse. La evidencia epidemiológica y experimental es cada vez mayor, y demuestra que hay una relación consistente entre la presencia de estos factores y los problemas que tienen cada vez más parejas en el mundo para concebir un hijo. Aunados al estilo de vida, en muchos países son frecuentes los problemas de contaminación que inciden en la infertilidad de la población. Esto hace fundamental crear conciencia. Aunque es cierto que las ciudades o zonas industrializadas es donde se observan estos problemas con mayor frecuencia, no son privativos ni se restringen a esos lugares, nos afectan a todos y, al menos en lo que concierne a la contaminación, todos podemos y debemos participar en la mejora de las condiciones de vida que van de la mano con nuestra salud reproductiva.

Abstract Infertility in couples has been increasing worldwide. There are a lot of causes involved in this issue, however one factor that is gaining a greater presence and importance is air pollution. Although both women and men can present alterations that prevent them from being fertile, this review describes two factors that are known to affect female reproductive health: lifestyle and environmental pollution. Lifestyle factors that affect reproductive health in women include smoking, obesity, stress, and deferment of motherhood. Regarding air pollution, it is known that organo-chlorinated pesticides, fossil fuel derivatives, polycyclic aromatic hydrocarbons, sulfur and nitrogen oxides, metals and suspended particles all produce adverse effects in the possibility of getting pregnant. The increasing body of epidemiological and experimental evidence shows a consistent relationship between the presence of these factors and the issues that a growing number couples around the world present to conceive a child. Along with the lifestyle, pollution is a common cause of infertility in the population in many countries of the world. Hence, it is essential to raise awareness in the population about these consequences. Although ,these problems are more frequently observed in cities or industrialized areas, they are not exclusive or restricted to these places, they affect us all, and at least as far as pollution is concerned, we all can and should participate in the improvement of our living conditions that go along with our reproductive health.

Oxidative Stress as a Mechanism Involved in Kidney Damage After Subchronic Exposure to Vanadium Inhalation and Oral Sweetened Beverages in a Mouse Model.

Kidney diseases have notably increased in the last few years. This is partially explained by the increase in metabolic syndrome, diabetes, and systemic blood hypertension. However, there is a segment of the population that has neither of the previous risk factors, yet suffers kidney damage. Exposure to atmospheric pollutants has been suggested as a possible risk factor. Air-suspended particles carry on their surface a variety of fuel combustion-related residues such as metals, and vanadium is one of these. Vanadium might produce oxidative stress resulting in the damage of some organs such as the kidney. Additionally, in countries like Mexico, the ingestion of sweetened beverages is a major issue; whether these beverages alone are responsible for direct kidney damage or whether their ingestion promotes the progression of an existing renal damage generates controversy. In this study, we report the combined effect of vanadium inhalation and sweetened beverages ingestion in a mouse model. Forty CD-1 male mice were distributed in 4 groups: control, vanadium inhalation, 30% sucrose in drinking water, and vanadium inhalation plus sucrose 30% in drinking water. Our results support that vanadium inhalation and the ingestion of 30% sucrose induce functional and histological kidney damage and an increase in oxidative stress biomarkers, which were higher in the combined effect of vanadium plus 30% sucrose. The results also support that the ingestion of 30% sucrose alone without hyperglycemia also produces kidney damage.

Pollution by metals: Is there a relationship in glycemic control?

There are evidences of environmental pollution and health effects. Metals are pollutants implicated in systemic toxicity. One of the least studied effects, but which is currently becoming more important, is the effect of metals on glycemic control. Metals have been implicated as causes of chronic inflammation and oxidative stress and are associated to obesity, hyperglycemia and even diabetes. Arsenic, iron, mercury, lead, cadmium and nickel have been studied as a risk factor for hyperglycemia and diabetes. There is another group of metals that causes hypoglycemia such as vanadium, chromium, zinc and magnesium by different mechanisms. Zinc, magnesium and chromium deficiency is associated with increased risk of diabetes. This review summarizes some metals involved in glycemic control and pretends to alert health professionals about considering environmental metals as an important factor that could explain the poor glycemic control in patients. Further studies are needed to understand this poorly assessed problem.

Sex-based differences in lymphocyte proliferation in the spleen after vanadium inhalation.

Vanadium (V) is a transition metal often adhered to particulate matter and released into the atmosphere as vanadium pentoxide (V2O5) by the burning of fossil fuels. This air pollutant causes adverse effects in the immune system. Lymphocytosis and splenomegaly have been reported with increased white pulp in mice after V inhalation. The effect of V on the immune system as related to sex has been poorly investigated. This study sought to determine if V inhalation (a) produced lymphoproliferation that could explain the changes previously observed in the spleen and in peripheral blood lymphocyte counts and (b) whether any observed effects differed due to gender. Immunohistochemical analyses of Ki-67, a specific proliferation marker, was made in the spleens of CD-1 male and female mice exposed for 1 h, twice a week, over a 12-week period to V2O5 (at 1.4 mg V2O5/m(3)) by whole-body inhalation; similar analyses were performed on spleens of control mice exposed to vehicle (filtered air). The results showed that in male mice there was a significant increase in percentage of Ki-67 immunopositive lymphocytes starting from the second week and until the end of the exposure. The Ki-67 signal was cytoplasmic and nuclear in the exposed males, while in controls the signal was only nuclear. In female mice, V inhalation singificantly increased the percentage of proliferating lymphocytes only after 1 week of exposure. Ki-67 signal was observed only in the nucleus of lymphocytes from the control and exposed females. The results here help to explain the splenomegaly and lymphocytosis observed previously in male mice and support the lymphoproliferative effect induced by V. Lastly, the finding that there was a sex difference in the effect of vanadium on lymphocyte proliferation suggests a role for sex hormones in potential protection against V immunotoxicity; however, further studies are needed to support this hypothesis.

Myocardial connexin-43 and N-Cadherin decrease during vanadium inhalation.

Particulate matter air pollution has considerably increased during the last decades; vanadium is a transition element adhered to this particulate matter, and the combustion of fossil fuels is the main source in the atmosphere. It has been reported that air pollution and specifically vanadium exposure increases the probability of suffering arrhythmias; however the biological mechanism of such a relationship remains unknown. It has been established that a diminished presence of N-Cadherin alters the Connexin-43 arrangement, and the consequent altered presence of these proteins predisposes to ventricular heart rate problems. We analyzed myocardial histology and the expression of N-Cadherin and Connexin-43 by immunohistochemistry in mouse that inhaled vanadium. Our results showed a significant and progressive reduction in both N-Cadherin and Connexin-43, as well as the presence of meganucleus; myofibrils disruption, and clumping in the exposed groups were also observed. Our findings add more information about a possible explanation for the arrythmogenic effect observed in dwellers of cities with high particulate matter atmospheric pollution.

Activation of Janus kinase/signal transducers and activators of transcription pathway involved in megakaryocyte proliferation induced by vanadium resembles some aspects of essential thrombocythemia.

Vanadium (V) is an air pollutant released into the atmosphere by burning fossil fuels. Also, it has been recently evaluated for their carcinogenic potential to establish permissible limits of exposure at workplaces. We previously reported an increase in the number and size of platelets and their precursor cells and megakaryocytes in bone marrow and spleen. The aim of this study was to identify the involvement of Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway and thrombopoietin (TPO) receptor, and myeloproliferative leukemia virus oncogene (Mpl), in megakaryocyte proliferation induced by this compound. Mice were exposed twice a week to vanadium pentoxide inhalation (0.02 M) and were killed at 4th, 6th, and 8th week of exposure. Phosphorylated JAK2 (JAK2 ph), STAT3 (STAT3 ph), STAT5, and Mpl were identified in mice spleen megakaryocytes by cytofluorometry and immunohistochemistry. An increase in JAK2 ph and STAT3 ph, but a decrease in Mpl at 8-week exposure was identified in our findings. Taking together, we propose that the morphological findings, JAK/STAT activation, and decreased Mpl receptor induced by V leads to a condition comparable to essential thrombocythemia, so the effect on megakaryocytes caused by different mechanisms is similar. We also suggest that the decrease in Mpl is a negative feedback mechanism after the JAK/STAT activation. Since megakaryocytes are platelet precursors, their alteration affects platelet morphology and function, which might have implications in hemostasis as demonstrated previously, so it is important to continue evaluating the effects of toxics and pollutants on megakaryocytes and platelets.