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.

Implementación del mini-CEX en el pregrado médico: Una experiencia con simulación / Implementation of the Mini-CEX in Medical Undergraduate Education: A Simulation-Based Experience

Resumen La evaluación es un proceso sistemático que resulta en un juicio de valor para tomar decisiones. Los instrumentos empleados para obtener datos sobre el desempeño de los estudiantes requieren de un proceso sistemático y objetivo para su implementación. El mini-CEX es un instrumento de observación directa que ha sido empleado para la evaluación de la competencia clínica en los estudiantes de pre y posgrado desde su invención en 1955. Cuenta con diferentes evidencias de validez para su uso en distintos contextos educativos y clínicos. Permite realizar evaluaciones rápidas, acompañadas de realimentación y que proporcionan información relevante del desarrollo de la competencia clínica. El objetivo de este escrito es exponer la experiencia de la implementación del mini-CEX en el pregrado médico para la evaluación formativa de los estudiantes utilizando la simulación con pacientes estandarizados. Para lograr este objetivo se empleó la siguiente secuencia: búsqueda, planeación, integración y aplicación. Posterior a estos pasos se dan una serie de recomendaciones para la implementación del mini-CEX. Se concluye que la evaluación de la competencia clínica es importante para la mejora continua y permanente de los estudiantes de pre y posgrado. Es necesario sistematizar la evaluación ajustada siempre a objetivos y necesidades específicas de la evaluación.

Abstract Evaluation is a systematic process that results in a judgment to make decisions. The instruments used to obtain data on student performance require a systematic and objective process for their implementation. The mini-CEX is a direct observation tool that has been used for the evaluation of clinical competence in undergraduate and postgraduate students since its invention in 1955. It has different validity evidence for use in different educational and clinical contexts. It allows rapid evaluations, accompanied by feedback and providing relevant information on the development of clinical competence. The objective of this paper is to expose the experience of the implementation of the mini-CEX in the medical undergraduate for the formative evaluation of students using simulation with standardized patients. To achieve this goal, the following sequence was used: search, planning, integration, and application. After these steps we make some recommendations for the implementation of the mini-CEX. Its is concluded that the evaluation of clinical competence is important for the continuous and permanent improvement of undergraduate and graduate students. It is necessary to systematize the evaluation always adjusted to objectives and specific needs of the evaluation.

Experiencias de docentes y estudiantes en la educación remota de emergencia: oportunidades para mejorar la educación del pregrado en medicina / Faculty and student experience during remote emergency education: opportunities for improving undergraduate medical education

Introducción: Los ciclos clínicos de pregrado representan los escenarios principales en los que los estudiantes de medicina consolidan los conocimientos. Sin embargo, a principios de 2020, la mayoría de los estudiantes fue confinada en sus domicilios debido a la pandemia por el SARS-CoV-2. Los procesos formativos continuaron desde los hogares por medio de la educación remota de emergencia, una modalidad de enseñanza basada en el uso intensivo de la tecnología que, a pesar de hacerse de manera improvisada, respondió a la situación educativa de urgencia. El propósito de este estudio fue indagar la experiencia educativa de estudiantes y docentes que se encontraban en los años clínicos de pregrado de la carrera de medicina con el fin de identificar las oportunidades de mejora en la enseñanza a partir de la crisis sanitaria vivida. Sujetos y métodos: Se realizó un estudio cualitativo de carácter descriptivo con la técnica de grupos focales. El análisis se basó en la reducción de datos, en la triangulación entre estamentos y en la bibliografía del tema. Resultados: Se realizaron 16 grupos focales con un total de 148 participantes. Se identificaron cuatro categorías generales: a) enseñanza y aprendizaje; b) evaluación de la práctica clínica; c) identidad profesional, y d) sugerencias en busca de mejoras en la formación de los médicos Conclusiones: Las reflexiones reconocen la necesidad de incorporar las tecnologías digitales de una manera planeada y diseñada en conjunto por expertos y docentes para adaptarlas a las necesidades de los contextos educativos, y continuar con modelos híbridos o combinados para mejorar la educación médica.(AU)

Introduction: During medical education, undergraduate clinical cycles represent the main scenarios where students consolidate knowledge. However, in the early 2020s, most students were confined to their homes due to the SARS-Cov-2 pandemic. In this situation, the digital network allowed the educational processes to continue from their homes through remote emergency education (REE), a teaching modality based on the intensive use of technology that, despite having been improvised, responded to the emergency educational situation. Therefore, this study aimed to investigate the educational experience of students and teachers in the undergraduate clinical years of the medical degree in order to identify opportunities for improvement in teaching after the health crisis. Subjects and methods: A descriptive qualitative study was carried out with a phenomenological approach through the focus group technique. The qualitative analysis was based on data reduction and triangulation between strata and subject literature. Results: Sixteen focus groups were integrated with a total of 148 participants. Four categories were identified: a) teaching and learning; b) evaluation of clinical practice; c) professional identity, and d) suggestions for improvement in the training of physicians. Conclusions: The reflections lead to recognizing the need to incorporate digital technology designed by experts and teachers to adapt them to the real needs of the educational contexts and to continue with a hybrid or combined model that supports the improvement of medical education.(AU)

Evaluation of the Anti-Toxoplasma gondii Efficacy, Cytotoxicity, and GC/MS Profile of Pleopeltis crassinervata Active Subfractions.

Pleopeltis crassinervata (Pc) is a fern that, according to ethnobotanical records, is used in Mexican traditional medicine to treat gastrointestinal ailments. Recent reports indicate that the hexane fraction (Hf) obtained from Pc methanolic frond extract affects Toxoplasma gondii tachyzoite viability in vitro; therefore, in the present study, the activity of different Pc hexane subfractions (Hsf) obtained by chromatographic methods was evaluated in the same biological model. Gas chromatography/mass spectrometry (GC/MS) analysis was carried out for hexane subfraction number one (Hsf1), as it showed the highest anti-Toxoplasma activity with a half-maximal inhibitory concentration (IC50) of 23.6 µg/mL, a 50% cytotoxic concentration (CC50) of 398.7 µg/mL in Vero cells, and a selective index (SI) of 16.89. Eighteen compounds were identified by Hsf1 GC/MS analysis, with the majority being fatty acids and terpenes. Hexadecanoic acid, methyl ester was the most commonly found compound (18.05%) followed by olean-13(18)-ene, 2,2,4a,8a,9,12b,14a-octamethyl-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,12,12a,12b,13,14,14a,14b-eicosahydropicene, and 8-octadecenoid acid, methyl ester, which were detected at 16.19%, 12.53%, and 12.99%, respectively. Based on the mechanisms of action reported for these molecules, Hsf1 could exert its anti-Toxoplasma activity mainly on T. gondii lipidomes and membranes.

Bioactive Peptides against Human Apicomplexan Parasites.

Apicomplexan parasites are the causal agents of different medically important diseases, such as toxoplasmosis, cryptosporidiosis, and malaria. Toxoplasmosis is considered a neglected parasitosis, even though it can cause severe cerebral complications and death in immunocompromised patients, including children and pregnant women. Drugs against Toxoplasma gondii, the etiological agent of toxoplasmosis, are highly toxic and lack efficacy in eradicating tissue cysts, promoting the establishment of latent infection and acute relapsing disease. Cryptosporidiosis has been recognized as the most frequent waterborne parasitosis in US outbreaks; anti-cryptosporidium drug discovery still faces a major obstacle: drugs that can act on the epicellular parasite. Severe malaria is most commonly caused by the progression of infection with Plasmodium falciparum. In recent years, great progress has been made in the field of antimalarial drugs and vaccines, although the resistance of P. falciparum to artemisinin has recently gained a foothold in Africa. As seen, the search for new drugs against these parasites remains a challenge. Peptide-based drugs seem to be attractive alternative therapeutic agents recently recognized by the pharmaceutical industry, as they can kill different infectious agents and modulate the immune response. A review of the experimental effects of bioactive peptides on these parasites follows, along with comments. In addition, some biological and metabolomic generalities of the parasites are reviewed to elucidate peptide mechanisms of action on Apicomplexan targets.

El tejido adiposo, ¿solo un almacén de energía? / Adipose Tissue, Just an Energy Storage?

Resumen Cuando los alimentos cubren los requerimientos energéticos, el organismo almacena el exceso de calorías como glucógeno en el hígado y el músculo, y los triacilgliceroles en el tejido adiposo. Morfológica y funcionalmente se clasifica en blanco y pardo. El pardo tiene gran cantidad de mitocondrias, almacena los triacilgliceroles en vacuolas y disipa la energía en forma de calor; el blanco almacena energía en gotas lipídicas que ocupan la mayor parte de su volumen. Después de la ingesta de alimentos se libera insulina, lo que hace que externen GLUT4 para absorber glucosa. Los quilomicrones o las lipoproteínas de muy baja densidad (VLDL) transportan los triacilgliceroles a los depósitos de tejido adiposo. Durante el ayuno, por acción del glucagón, se liberan enzimas que degradarán a los tri, di y monogliceroles para liberar a los ácidos grasos. El tejido adiposo libera citocinas pro y antiinflamatorias, así como leptina, adiponectina que regulan el apetito y la saciedad. La proteína cinasa activada por AMP se activa como respuesta a una baja en la cantidad de energía de la célula y le ayuda a mantener un balance energético. En el adipocito promueve la degradación de los triacilgliceroles para liberar a los ácidos grasos que se emplearán como fuente energética. Se requiere de mayor cantidad de estudios para conocer más sobre la función del tejido adiposo como regulador del metabolismo y no solo como almacén de energía.

Abstract When food meets energy requirements, the body stores in the liver and in the muscle the excess of calories as glycogen and triacylglycerols in the adipose tissue. Morphologically and functionally, it is classified into white and brown tissues. Brown tissue has many large mitochondria and stores triacylglycerols in vacuoles and dissipates energy as heat; white tissue stores energy as lipid droplets that occupy most of the adipocyte's volume. After food intake insulin is released, which causes GLUT4 externalization into the cellular membrane to absorb glucose. Chylomicrons or VLDL transport triacylglycerols to adipose tissue depots. During fasting, by the action of glucagon, enzymes are released that will degrade tri-, di- and mono-glycerols to release fatty acids. Adipose tissue releases pro and anti-inflammatory cytokines, as well as leptin and adiponectin that regulate appetite and satiety. AMPK is activated in response to a decrease in the cell's energy and helps it to maintain its energetic balance. In the adipocyte, it promotes the degradation of triacylglycerols releasing fatty acids to be used as an energy source. More studies are needed to learn more about the function of adipose tissue as a regulator of the metabolism and not only as an energy storage.

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.

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.

Evaluation of the genotoxicity, cytotoxicity and antimalarial effect of sodium metavanadate po in a Plasmodium yoelii yoelii infected murine model.

Malaria is a parasitic disease with the highest morbidity and mortality worldwide and antimalarial drug resistance has increased in last two decades. Chloroquine and artemisinin which were usedfor the treatment of malaria are also reported with resistances. Recently, some metallic compounds of ruthenium and iridium have been used as possible therapeutic agents against other parasites such as Leishmania and Trypanosoma cruzi. Organic and inorganic compounds of vanadium such as metavanadate, have been used lately because its therapeutic properties as antineoplastic and hypoglycemic agents. In this study we evaluated the genotoxicity and cytotoxicity of metavanadate per os and its working dose, as a previous step for the future use of metavanadate as anti-parasitic agent in a Plasmodium yoelii yoelii malarial lethal model. Our findings suggest that 10 mg/kg is a safe dose that decreases parasitemia and increases the survival of the Plasmodium yoelii yoelii infected mice with no evidence of genotoxicity, cytotoxicity with the dose selected.

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.

Toxicity of silver nanoparticles in mouse bone marrow-derived dendritic cells: Implications for phenotype.

Silver nanoparticles (AgNP) are one of the most studied nanoparticles due to their anti-bacterial, -fungal, -viral, -parasitic, and -inflammatory properties. This raises the need to evaluate the toxicity and biological effects of AgNP in the immune system in order to develop new safer biomedical products. In this study, an AgNP formulation currently approved for veterinary applications was applied to mouse bone marrow-derived dendritic cells (BMDC), considered important antigen-presenting cells of the immune system, to evaluate cytotoxicity, genotoxicity, and any significant influence on expression of cellular markers associated with BMDC phenotype and maturation status. The results showed that after 12 h of AgNP exposure, a significant decrease in BMDC viability occurred at the highest concentration tested (1.0 µg AgNP/ml) and at lower doses, the cells maintained membrane integrity and metabolic activity. DNA damage was not significant with any AgNP level aside from the 1.0 µg AgNP/ml level. Regarding phenotype, no differences in expression of CD40 (co-stimulatory molecule highly present in mature BMDC) or in CD273 (a marker for inhibitory T-cell response) were observed. The current results showed that the toxicity of this AgNP formulation was dose-related. The findings also suggest BMDC could maintain structural conservation of co-stimulatory/co-inhibitory surface molecules after 12 h of exposure to this AgNP. This work represents the first step in identifying the toxic effects of this AgNP formulation on dendritic cells.

Vanadium compounds and cellular death mechanisms in the A549 cell line: The relevance of the compound valence.

Non-small lung cell carcinoma has a high morbidity and mortality rates. The elective treatment for stage III and IV is cisplatinum that conveys serious toxic side effects. Vanadium compounds are metal molecules with proven antitumor activity that depends on its valence. Therefore, a better understanding of the mechanism of action of vanadium compounds is required. The aim of our study was to investigate the mechanisms of cell death induced by sodium metavanadate (NaVO3 [V(+5)]) and vanadyl sulfate (VOSO4 [(+4)]), both of which have reported apoptotic-inducing activity. We exposed the A549 cell line to various concentrations (0-100 µM) and to different exposure times to each compound and determined the cell viability and expression of caspases, reactive oxygen species (ROS) production, Bcl2, Bax, FasL and NO. Our results showed that neither compounds modified the basal expression of caspases or pro- and anti-apoptotic proteins. The only change observed was the 12- and 14-fold significant increase in ROS production induced by NaVO3 and VOSO4 , respectively, at 100 µm concentrations after 48 hours. Our results suggest that classical apoptotic mechanisms are not related to the cell death induced by the vanadium compounds evaluated here, and showed that the higher ROS production was induced by the [(+4)] valence compound. It is possible that the difference will be secondary to its higher oxidative status and thus higher ROS production, which leads to higher cell damage. In conclusion, our results suggest that the efficacy of the cell death mechanisms induced by vanadium compounds differ depending on the valence of the compound.

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.

Histopathological alterations in mice under sub-acute treatment with Hintonia latiflora methanolic stem bark extract.

The indiscriminate use of herbal products is increasingly growing worldwide; nonetheless consumers are not warned about the potential health risks that these products may cause. Hintonia latiflora (Hl) is a tree native to the American continent belonging to the Rubiaceae family and its stem bark is empirically used mainly to treat diabetes and malaria; supplements containing Hl are sold in America and Europe without medical prescription, thus scientific information regarding its toxicity as a consequence of a regular consumption is needed. In the present study, the histopathological effect of 200 and 1000 mg/kg of HI methanolic stem bark extract (HlMeOHe) was evaluated in the small bowel, liver, pancreas, kidneys and brain of CD-1 male mice after oral sub-acute treatment for 28 days. No histopathological alterations were observed in the brain and small bowel of the treated animals; however, mice presented diarrhea from day 2 of treatment with both doses. No histological changes were observed in the tissues collected from the animals treated with 200 mg/kg, except for the liver that depicted periportal hepatitis. Animals treated with the higher dose showed in the liver sections hydropic degeneration, hepatitis and necrosis, kidney sections depicted tubular necrosis and in pancreas sections, hydropic degeneration of the pancreatic islets was observed. In conclusion, HlMeOHe damaged the liver with an oral dose of 200 mg/kg, and at 1000 mg/kg injured the kidneys and pancreas of the CD-1 male mice.

Lead inhalation and hepatic damage: Morphological and functional evaluation in mice.

Lead (Pb) is a heavy metal that plays an unknown biological role and is very toxic even at low concentrations. The main sources of Pb are Pb-contaminated areas in industrial areas or landfills. Inhalation is one of the most common routes of exposure to this metal, but there is little information on its effect on the liver. Thirty male mice were exposed to 0.1 M Pb acetate by inhalation for 8 weeks, twice a week for 1h. A recovery group was free of exposure for 4 weeks. Histological evaluation showed an increase in the inflammatory infiltrate and in the percentage of meganuclei in the liver. This was observed since the first week and throughout the whole exposure time. A significant increase in the aspartate aminotransferase concentration was observed in the liver function tests; yet, the alanine aminotransferase concentration did not show significant changes. The 4-hydroxynonenal (4-HNE) and nitrotyrosine levels in Pb-exposed mice, identified by immunohistochemistry, showed a significant increment compared to the controls. This effect was observed throughout Pb exposure. After a 4-week period of suspended exposure, recovery time, the concentration of 4-HNE and nitrotyrosine decreased to similar levels of those previously observed in controls, this suggests a decrease in the generation of oxidative stress by Pb inhalation. Although our results suggest that the lungs are the first contact organs and filters during Pb inhalation, this metal eventually reaches the liver and might cause damage by oxidative stress. This damage can decrease in time if exposure is discontinued.

Vanadium inhalation induces retinal Müller glial cell (MGC) alterations in a murine model.

BACKGROUND: Vanadium (V) is a transition metal adhered to suspended particles. Previous studies demonstrated that V inhalation causes oxidative stress in the ependymal epithelium, the choroid plexus on brain lateral ventricles and in the retina. Inhaled-V reaches the eye´s retina through the systemic circulation; however, its effect on the retina has not been widely studied. The Müller glial cell provides support and structure to the retina, facilitates synapses and regulates the microenvironment and neuronal metabolism. Hence, it is of great interest to study the effect of V exposure on the expression and localization of specific biomarkers on this cell. METHODS: Male CD-1 mice were exposed to V inhalation 1 h/twice/week for 4 and 8-Wk. Expression changes in the retina of Glial fibrillary acidic protein, highly expressed in Müller glial cell when retina is damaged, and Glutamine synthetase, important in preventing excitotoxicity in the retina, were analysed by immunohistochemistry. RESULTS: Glial fibrillary acidic protein expression increased at 4-Wk of V inhalation compared to the control and decreased at 8-Wk of exposure. A time-dependent gradual reduction in glutamine synthetase expression was observed. CONCLUSION: Changes in glial fibrillary acidic protein expression induced by V suggest retinal damage, whereas glutamine synthetase gradual reduction might indicate that photoreceptors, which produce most of the glutamine synthetase substrate in the retina, are degenerating, probably as a consequence of the oxidative stress induced by V.

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.