Adverse neurological effects after exposure to copper, manganese, and mercury mixtures in a Spraque-Dawley rat model: an ultrastructural investigation.

Exposure to environmental metal pollutants is linked to oxidative stress and the subsequent development of neurological disease. In this study, the effects of copper, manganese, and mercury, were evaluated at X100 the World Health Organization safety limits for drinking water. Using a Sprague-Dawley rat model, following exposure for 28 days, the effects of these metals on biochemical blood parameters and tissue and cellular structure of the brain were determined. Biochemical analysis revealed no hepatocellular injury with minor changes associated with the hepatobiliary system. Minimal changes were found for renal function and the Na+/K+ ratio was reduced in the copper and manganese (Cu + Mn) and copper, manganese, and mercury (Cu, Mn + Hg) groups that could affect neurological function. Light microscopy of the brain revealed abnormal histopathology of Purkinje cells in the cerebellum and pyramidal cells in the cerebrum as well as tissue damage and fibrosis of the surface blood vessels. Transmission electron microscopy of the cerebral neurons showed microscopic signs of axonal damage, chromatin condensation, the presence of indistinct nucleoli and mitochondrial damage. Together these cellular features suggest the presence and influence of oxidative stress. Exposure to these metals at X100 the safety limits, as part of mixtures, induces changes to neurological tissue that could adversely influence neurological functioning in the central nervous system.

Adverse cardiovascular effects of exposure to cadmium and mercury alone and in combination on the cardiac tissue and aorta of Sprague-Dawley rats.

The aim of this study was to identify cardiovascular effects of relevant concentrations of Cd and Hg alone and in combination as a mixture in water. This was achieved by administering to male Sprague-Dawley rats via gavage 0.62 mg/kg Cd or 1.23 mg/kg Hg, or a combination of 0.62 mg/kg Cd and 1.23 mg/kg Hg in the co-exposure group for 28 days. Concentrations were the rat equivalence dosages of 1,000 times the World Health Organization's limits of 0.003 mg/L and 0.006 mg/L for Cd and Hg, respectively, for water. With termination, blood levels of the metals were increased. For all metal exposed groups, histological evaluation and transmission electron microscopy of the myocardium revealed myofibrillar necrosis, increased fibrosis, vacuole formation and mitochondrial damage. Cd caused the most mitochondrial damage while Hg to a greater degree induced fibrosis. In the aorta, both Cd and Hg also increased collagen deposition adversely altering the morphology of the fenestrated elastic fibers in the tunica media. Co-exposure resulted in increased cardiotoxicity with increased mitochondrial damage, fibrosis and distortion of the aortic wall as a result of increased collagen deposition, as well as altered elastin deposition, fragmentation and interlink formation. These are typical features of oxidative damage that correlates with a phenotype of premature ageing of the CVS that potentially can lead to hypertension and premature cardiac failure.

Induction of hepatic portal fibrosis, mitochondria damage, and extracellular vesicle formation in Sprague-Dawley rats exposed to copper, manganese, and mercury, alone and in combination.

Increased anthropogenic activity and subsequent environmental exposure to heavy metals induce the production of reactive oxygen species (ROS), which increases oxidative stress and the risk of associated diseases. The aim of this study, in a subacute model of toxicity, was to investigate the effects of copper (Cu), manganese (Mn), and mercury (Hg) alone and in combination on the liver tissue of male Sprague-Dawley rats, exposed orally to 100 times the World Health Organization's acceptable water limits of each metal. General histological alterations as well as ultrastructural changes were investigated using light microscopy and transmission electron microscopy (TEM) respectively. Exposure to Cu, Mn, and Hg, alone and in combinations, caused hydropic swelling of the hepatocytes, dilation of the sinusoids, formation of binucleated hepatocytes with an increased inflammatory cell accumulation at the portal triad. Increased collagen deposition with associated fibrosis was also observed. Evaluation of hepatocyte ultrastructure revealed mitochondrial membrane damage and inner membrane swelling especially for hepatocytes exposed to Mn. Extracellular vesicle (EV) formation was observed in the liver tissue of all exposed rats. Furthermore, increased damage observed for metal combinations was possibly due to synergism. In conclusion, Cu, Mn, and Hg alone and as part of a mixture cause cellular damage, inflammation, and fibrosis increasing the risk of associated diseases.

Ultrastructural alterations of whole blood by copper, manganese and mercury metal mixtures using a chronic in vivo model of coagulation.

Globally, contamination of drinking water by heavy metals is increasing and poses a potential hazard to human health. Data on heavy metal mixtures and their effects on thrombosis are limited. The objective of this study was to determine the in vivo effects that copper, manganese and mercury, alone and in mixtures, have on clotting potential. Forty-eight male Sprague-Dawley rats were divided into eight groups, dependent on the type of heavy metal/s administered. The dosages were calculated at X100 the World Health Organisation limits in drinking water and orally administered for 28 days, at the University of Pretoria in 2018. Heavy metal induced morphological alterations of erythrocytes, platelets and fibrin networks were evaluated, using scanning electron microscopy. The manganese and mercury mixture had the greatest thrombotic potential by inducing acanthocyte and echinocyte formation, generating highly activated platelets with spontaneous fibrin formation and forming a disorganised fibrin network. In conclusion, chronic or single high dosage exposure to these heavy metals can potentially induce or contribute to thrombosis.

Oral exposure to cadmium and mercury alone and in combination causes damage to the lung tissue of Sprague-Dawley rats.

Environmental presence and human exposure to heavy metals in air and cigarette smoke has led to a worldwide increase in respiratory disease. The effects of oral exposure to heavy metals in liver and kidney structure and function have been widely investigated and the respiratory system as a target is often overlooked. The aim of the study was to investigate the possible structural changes in the lung tissue of Sprague-Dawley rats after oral exposure for 28 days to cadmium (Cd) and mercury (Hg), alone and in combination at 1000 times the World Health Organization's limit for each metal in drinking water. Following exposure, the general morphology of the bronchiole and lungs as well as collagen and elastin distribution was evaluated using histological techniques and transmission electron microscopy. In the lungs, structural changes to the alveoli included collapsed alveolar spaces, presence of inflammatory cells and thickening of the alveolar walls. In addition, exposure to Cd and Hg caused degeneration of the alveolar structures resulting in confluent alveoli. Changes in bronchiole morphology included an increase in smooth muscle mass with luminal epithelium degeneration, detachment and aggregation. Prominent bronchiole-associated lymphoid tissue was present in the group exposed to Cd and Hg. Ultrastructural examination confirmed the presence of fibrosis where in the Cd exposed group, collagen fibrils arrangement was dense, while in the Hg exposed group, additional prominent elastin was present. This study identified the lungs as target of heavy metals toxicity following oral exposure resulting in cellular damage, inflammation and fibrosis and increased risk of respiratory disease where Hg showed the greatest fibrotic effect, which was further, aggravated in combination with Cd.

Ultrastructural, Confocal and Viscoelastic Characteristics of Whole Blood and Plasma After Exposure to Cadmium and Chromium Alone and in Combination: An Ex Vivo Study.

BACKGROUND/AIMS: Heavy metal pollution is increasing in the environment, contaminating water, food and air supplies. This can be linked to many anthropogenic activities. Heavy metals are absorbed through the skin, inhalation and/or orally. Irrespective of the manner of heavy metal entry in the body, the blood circulatory system is potentially the first to be affected following exposure and adverse effects on blood coagulation can lead to associated thrombotic disease. Although the plasma levels and the effects of cadmium (Cd) and chromium (Cr) on erythrocytes and lymphocytes have been described, the environmental exposure to heavy metals are not limited to a single metal and often involves metal mixtures, with each metal having different rates of absorption, different cellular, tissue, and organ targets. Therefore the aim of this study is to investigate the effects of the heavy metals Cd and Cr alone and whether Cr synergistically increases the effect of Cd on physiological important processes such as blood coagulation. METHODS: Human blood was exposed to the heavy metals ex vivo, and thereafter morphological analysis was performed with scanning electron- and confocal laser scanning microscopy (CLSM) in conjunction with thromboelastography®. RESULTS: The erythrocytes, platelets and fibrin networks presented with ultrastructural changes, including varied erythrocytes morphologies, activated platelets and significantly thicker fibrin fibres in the metal-exposed groups. CLSM analysis revealed the presence of phosphatidylserine on the outer surface of the membranes of the spherocytic erythrocytes exposed to Cd and Cr alone and in combination. The viscoelastic analysis revealed only a trend that indicates that clots that will form after heavy metal exposure, will likely be fragile and unstable especially for Cd and Cr in combination. CONCLUSION: This study identified the blood as an important target system of Cd and Cr toxicity.

Effects of chronic exposure to mercury and cadmium alone and in combination on the coagulation system of Sprague-Dawley rats.

Water contamination with heavy metals may adversely affect our health. High metal levels lead to changes in blood coagulation processes, increasing the risk for cardiovascular disease. Exposure is not limited to a single metal but usually involves a mixture of metals. In this study 24 male Sprague-Dawley rats were exposed to cadmium (Cd) and mercury (Hg), alone and in combination, for 28 days at dosages equivalent to 1000 times the World Health Organization water limits. Scanning electron microscopy analysis revealed that both metals caused platelet activation. Cd significantly increased fibrin fibers thickness and caused aggregation and formation of dense matted deposits (DMDs). Hg reduced fibrin network formation. In the combination group, Hg appeared to augment the effect of Cd, and the presence of extensive DMDs or aggregates between the fibers, with no changes to the actual fibrin thickness, was observed.

Effects of metals cadmium and chromium alone and in combination on the liver and kidney tissue of male Spraque-Dawley rats: An ultrastructural and electron-energy-loss spectroscopy investigation.

Heavy metal pollution has increased in the last decades. Water sources are contaminated and human exposure is often long term exposure to variable amounts of different metals. In this study, male Sprague-Dawley rats were exposed via oral gavage for 28 days to cadmium (Cd) and chromium (Cr), alone and in combination at concentrations 1000 times the human World Health Organization's acceptable water limits. Rat equivalent dosages were used. Blood markers of liver and kidney function were measured, changes to cellular morphology was determined with transmission electron microscopy and the intracellular metal localisation was determined with the electron energy-loss spectroscopy and energy filtered transmission electron microscopy analysis. Both Cd and Cr caused changes to the nuclear and mitochondrial membranes and irregular chromatin condensation of hepatocytes. Cr exposure caused dilation of the rough endoplasmic reticulum (rER). The combination caused nuclear and mitochondrial membrane damage as well as irregular chromatin condensation. In the kidney tissue, Cd caused irregular chromatin condensation in the cells of the proximal convoluted tubule (PCT). Cr caused changes to the outer nuclear and mitochondrial membrane and chromatin structure. The combination group caused membrane damage, irregular chromatin condensation and rER changes in the PCT. All the metal groups showed damage to the endothelial cells and pedicles, but not to the mesangial cells. Cd and Cr bio-accumulation was observed in the nucleus, mitochondria and rER of the liver and kidney and therefore are responsible for the cellular observed damage that can cause functional changes to the tissues and organs.

How methylglyoxal kills bacteria: An ultrastructural study.

Antibacterial activity of honey is due to the presence of methylglyoxal (MGO), H2O2, bee defensin as well as polyphenols. High MGO levels in manuka honey are the main source of antibacterial activity. Manuka honey has been reported to reduce the swarming and swimming motility of Pseudomonas aeruginosa due to de-flagellation. Due to the complexity of honey it is unknown if this effect is directly due to MGO. In this ultrastructural investigation the effects of MGO on the morphology of bacteria and specifically the structure of fimbriae and flagella were investigated. MGO effectively inhibited Gram positive (Bacillus subtilis; MIC 0.8 mM and Staphylococcus aureus; MIC 1.2 mM) and Gram negative (P. aeruginosa; MIC 1.0 mM and Escherichia coli; MIC 1.2 mM) bacteria growth. The ultrastructural effects of 0.5, 1.0 and 2 mM MGO on B. substilis and E. coli morphology was then evaluated. At 0.5 mM MGO, bacteria structure was unaltered. For both bacteria at 1 mM MGO fewer fimbriae were present and the flagella were less or absent. Identified structures appeared stunted and fragile. At 2 mM MGO fimbriae and flagella were absent while the bacteria were rounded with shrinkage and loss of membrane integrity. Antibacterial MGO causes alterations in the structure of bacterial fimbriae and flagella which would limit bacteria adherence and motility.

A descriptive study to provide evidence of the teratogenic and cellular effects of sibutramine and ephedrine on cardiac- and liver-tissue of chick embryos.

Exposure to drugs during pregnancy is a major concern, as some teratogenic compounds can influence normal foetal development. Although the use of drugs during pregnancy should generally be avoided, exposure of the developing foetus to teratogens may occur unknowingly since these compounds may be hidden in products that are being marketed as "all natural." The aim of the current study was to investigate the possible teratogenic and cellular effects of sibutramine-a serotonin-norepinephrine reuptake inhibitor used in the treatment of obesity-on the heart and liver tissue of chick embryos. Ephedrine was used as a positive control. The chick embryo model was chosen because it has been used in studying developmental and experimental biology and teratology with great success. The embryos were exposed to three different concentrations of sibutramine and ephedrine respectively. The results obtained revealed that both compounds exhibited embryotoxicity when compared to the control groups. Liver and heart tissue of the exposed embryos was severely affected by these compounds in a dose-related manner. Morphology similar to that of muscle dystrophy was observed in the heart, where the muscle tissue was infiltrated by adipose and connective tissue. Severe liver steatosis was also noted. A more in-depth investigation into the molecular pathways involved might provide more information on the exact mechanism of toxicity of these products influencing embryonic development.

Sibutramine, a serotonin-norepinephrine reuptake inhibitor, causes fibrosis in rats.

Sibutramine hydrochloride monohydrate is a weight loss agent indicated for the treatment of obesity. Although it has been banned from most markets, studies are still relevant as it is often a hidden ingredient in herbal and over the counter slimming products. Sibutramine induces liver fibrosis with steatosis in female Sprague-Dawley rats fed a high-energy diet without significant weight gain. In this study, using the same animal model, the effect of Sibutramine on lung morphology was investigated using histological evaluation of the terminal bronchiole and transmission electron microscopy evaluation of the respiratory tissue. From these results Sibutramine was found to induce lung fibrosis in Sprague-Dawley rats as increased collagen synthesis, mast cell accumulation and aggregates of Bronchus Associated Lymphoid Tissue (BALT) in the terminal bronchiole as well as increased collagen deposition in the respiratory tissue was seen.

Premature collagen fibril formation, fibroblast-mast cell interactions and mast cell-mediated phagocytosis of collagen in keloids.

Keloids are benign hyper-proliferative growths of fibrous tissue where increased fibroblast activity results in abnormal collagen deposition. Excessive inflammation is a characteristic feature of keloids, but little is known about the underlying ultrastructural features of keloids related to collagen processing, fibril and fiber formation, the interaction between fibroblasts and associated collagen fibers and mast cells. In this study, the ultrastructure of the dermis of keloid patients was evaluated using light and transmission electron microscopy techniques. Abnormal intracellular premature collagen fibril formation was observed. Phagocytosis of collagen fibrils by mast cells was a common ultrastructural feature of keloid tissue as was a close or direct association between fibroblasts and mast cells. Based on these findings and recent advances in knowledge related to collagen synthesis, fibril formation and processing, we hypothesize that keloid formation is primarily due to abnormal collagen synthesis where the consequent accumulation of collagen fibers causes increased mast cell recruitment and collagen phagocytosis. Subsequent release of mast cell-derived mediators then promotes further collagen synthesis. The observation of early formation in keloid tissue of premature insoluble collagen fibrils supports previous studies that enzymes such as procollagen C-proteinase are important early therapeutic targets.

The effect of sibutramine, a serotonin-norepinephrine reuptake inhibitor, on platelets and fibrin networks of male Sprague-Dawley rats: a descriptive study.

Sibutramine is used in the treatment of obesity due to its ability to influence feelings of hunger and satiety by inhibiting the re-uptake of serotonin and noradrenalin in the central nervous system (CNS). Sibutramine use has been associated with numerous adverse events in particular cardiovascular complications possibly due to the formation of thrombi. This ultrastructural descriptive study investigated the effect of sibutramine on blood coagulation, specifically the effect on morphology of platelets and fibrin networks using scanning electron microscopy. Male Sprague-Dawley rats treated with either a recommended therapeutic dose [low dosage 1.32 mg/kg] or a toxicological higher dose [high dosage 13.2 mg/kg] of sibutramine for 28 days were used and compared to control animals. Blood samples were collected and plasma smears were prepared for platelet evaluation. Following the addition of thrombin to the plasma samples, the morphology of the fibrin clots was evaluated. Platelet evaluation by scanning electron microscopy revealed morphology typical of a prothrombotic state with a characteristic excessive platelet activation in both low-dose (LD) and high-dose (HD) rats. The fibrin clots of sibutramine-treated rats, LD and HD revealed fused thick fibers with thin fibers forming a net-like structure over the thick fibers which differ considerably from the organized structure of the control animals. It can be concluded that sibutramine alters the ultrastructure of platelets and fibrin networks creating a prothrombotic state.

Feasibility of high pressure freezing with freeze substitution after long-term storage in chemical fixatives.

Fixation of biological samples is an important process especially related to histological and ultrastructural studies. Chemical fixation was the primary method of fixing tissue for transmission electron microscopy for many years, as it provides adequate preservation of the morphology of cells and organelles. High pressure freezing (HPF) and freeze substitution (FS) is a newer alternative method that rapidly freezes non-cryoprotected samples that are then slowly heated in the FS medium, allowing penetration of the tissue to insure adequate fixation. This study addresses several issues related to tissue preservation for electron microscopy. Using mice liver tissue as model the difference between samples fixed chemically or with HPF immediately after excision, or stored before chemical or HPF fixation were tested with specific focus on the nuclear membrane. Findings are that immediate HPF is the method of choice compared to chemical fixation. Of the chemical fixatives, immediate fixation with 2.5% glutaraldehyde (GA)/formaldehyde (FA) is the best in preserving membrane morphology, 2.5% GA can be used as alternative for stored and then chemically processed samples, with 10% formalin being suitable as a storage medium only if followed by HPF fixation. Overall, storage leads to lower ultrastructural preservation, but HPF with FS can minimize these artifacts relative to other processing protocols.

Rats on a high-energy diet showing no weight gain present with ultrastructural changes associated with liver fibrosis.

Sibutramine is widely used as a weight-loss substance in the treatment of obesity and is a selective inhibitor of the neuronal reuptake of serotonin and noradrenaline. Although banned, it is often a hidden ingredient in herbal and dietary supplements that are widely used by the general public. Various weight loss products, including sibutramine, have successfully been tested in animal models of diet-induced obesity. In the female Sprague-Dawley rat model, fed a high-energy diet that did not produce a significant increase in BMI, the cellular structure of the liver was evaluated using transmission electron microscopy. Compared to controls showing no damage, the livers of rats fed a high-energy diet were found to have increased fibrosis without steatosis, while for rats fed high-energy diet with sibutramine, fibrosis was increased and steatosis had developed. In conclusion, in female rats fed a high-energy diet that does not result in weight gain hepatic fibrosis occurs without steatosis. In these rats the co-administration of sibutramine increases the degree of fibrosis and steatosis develops. Although it has been widely believed that sibutramine is not hepatotoxic, this study clearly shows that at an ultrastructural level, rats fed a high-energy diet treated with sibutramine show signs of hepatotoxicity.

The effect of sibutramine on platelet morphology of Spraque-Dawley rats fed a high energy diet.

The aim of this study was to investigate the effect of Sibutramine on platelet ultrastructure and discuss the morphological observations in relation to known physiological effects of the compound. Six-week-old, female Spraque-Dawley rats were used in this study. The animals were placed on a high energy diet after which sibutramine administration followed. Blood was drawn on the day of termination and platelet rich plasma was obtained to prepare plasma smears for analysis. Scanning electron microscopy was used to investigate the ultrastructure of the platelets. Platelets of the Sibutramine-treated animals showed smooth surface with limited pseudopodia formation when compared with that of the control animals. Higher magnification of the platelet surface showed membrane tears and swelling, typically seen in necrotic cells. It can therefore be concluded from these results that Sibutramine alters the membrane morphology of platelets to that typical of necrotic cells.

Iron enhances generation of fibrin fibers in human blood: implications for pathogenesis of stroke.

Stroke is associated with the intracerebral formation of fibrin clots which may lead to irreversible brain damage. Thrombolytic therapies employ a variety of natural and/or recombinant plasminogen activators to initiate fibrinolytic degradation of cerebral thrombi. However, such therapies when installed beyond 4- to 6-h window, may fail to achieve the expected outcome. This is due to the hydroxyl radical-induced modification of fibrin(ogen) molecules rendering them refractory to fibrinolytic degradation, but no cause of the increased free radical generation in stroke was offered. Here, we show by means of electron microscopy that iron ions added to human blood dramatically enhances fibrin fibers formation with thrombin, and significantly delays fibrinolysis during spontaneous clotting of native blood. Iron ions caused the appearance dense matted fibrin deposits, similar, if not identical, to those observed in plasma of patients with stroke. These results may explain a known relationship between thrombotic diseases and the increased body concentrations of free iron and/or hemoglobin derivatives. We conclude that any action resulting in the inhibition of hemostatic abnormalities, as well as in the reduction of body free iron and scavenging of hydroxyl radicals (e.g., by polyphenols) can potentially prevent pathological reactions associated with consequences of stroke.

Scanning electron microscopy of fibrin networks in rheumatoid arthritis: a qualitative analysis.

Rheumatoid arthritis is a chronic inflammatory condition that affects mainly synovial joints and has an impact on approximately 1% of the Western population. The coagulation process is altered in this condition, and this is frequently complicated by thrombocytosis. Changes in fibrin morphology have been linked with inflammation, and this, in turn, plays an important role in thrombosis. Changes in the fibrin fiber formation cause the alterations observed in thrombus morphology. In the current study, the ultrastructure of platelets and fibrin networks was investigated to determine whether any morphological changes are present in these structures in patients suffering from rheumatoid arthritis. Six patients diagnosed with rheumatoid arthritis took part in this study, and their clot morphology was compared to that of control subjects. Citrated blood with and without the addition of thrombin was used. Results indicated that the fibrin networks in the arthritis patients formed thick, matted layers. This matted appearance is due to a changed ultrastructure of the minor, thin fibers. Also, in these patients, spontaneous networks were created without the addition of thrombin, which indicates an abnormal hemostatic protein functioning, and the latter is expressed as visible changes in ultrastructure.

The morphological effects of asthma, as well as conventional and alternative asthma therapies on parietal and chief cells in the stomach of BALB/c Mice / Los efectos morfológicos del asma, así como de las terapias convencionales y alternativas del asma sobre las células parietales y principales en el estómago de ratones Balb/c

Scientific literature, although limited in this area, supports the hypothesis that asthma, by means of selective leukocyte trafficking between the various mucosal and glandular sites of the body, can have the same pathophysiological effects on the stomach as the airways. This study aimed to determine if asthma, in the absence and presence of various asthma therapies (Hydrocortisone and Modul8TM), imparted any morphological alteration on the stomach parietal and chief cells. The BALB/c murine asthmatic mouse model was the model of choice in this study. The asthma induction protocol as well as the asthma therapies were proved to be effective with the aid of bronchial lavage fluid leukocyte quantification. Fundic and pyloric biopsies were extracted at termination and assessed by means of transmission electron, scanning electron and light microscopy. The extracted fundic and pyloric biopsies revealed asthma alone induced parietal cell hypertrophy (increase in parietal cell size P < 0.000100 in both stomach regions) and chief cell hyper functioning. The use of Hydrocortisone and Modul8TM, as a therapy to correct the perceived gastric alterations were dismal; only in the case of fundic parietal cells were both treatments able to compensate for the hypertrophic effect caused by asthma, while in the pylorus parietal cell asthma- induced hypertrophy was only compensated for by Modul8TM.

La literatura científica, aunque limitada en esta área, apoya la hipótesis de que el asma, por medio del tráfico selectivo de leucocitos entre los diferentes sitios y la mucosa glandular del cuerpo, puede tener los mismos efectos fisiopatológicos en el estómago y las vías respiratorias. Este estudio tuvo como objetivo determinar si el asma, en ausencia y presencia de diversos tratamientos para el asma (hidrocortisona y Modul8 TM), generó alguna alteración morfológica en las céluals parietales y principales del estómago. El modelo murino BALB/c del ratón asmático fue el modelo de elección en este estudio. El protocolo de inducción de asma, así como el tratamiento del asma demostró ser eficaz con la ayuda de lavado bronquial y cuantificación leucocitaria del fluido. Biopsias de las regiones fúndica y pilórica fueron extraídas y evaluadas por medio de microscopía electrónica de transmisión, de barrido y de luz. Las biopsias extraídas de la región fúndica y pilórica revelaron que el asma solamente induce hipertrofia de las células parietales (aumento del tamaño de las células parietales P <0,00001 en ambas regiones del estómago) e hiperfuncionamiento de las células principales. El uso de hidrocortisona y Modul8 TM, como una terapia para corregir las alteraciones gástricas fue disimil, sólo en el caso de las células parietales fúndicas ambos tratamientos fueron capaces de compensar el efecto hipertrófico causado por el asma, mientras que en la célula parietal pílorica la hipertrofia inducida por el asma solamente se vio compensada por Modul8TM.

Ultrastructural analyses of platelets and fibrin networks in BALB/c mice after inhalation of spherical and rod-shaped titanium nanoparticles / Análisis ultraestructural de plaquetas y redes de fibrina en ratones BALB/c después de la inhalación de nanopartículas de titanio con forma esférica y de barra

Engineered nanoparticles are designed to perform specific functions and therefore have specific properties that could potentially be harmful. Nanoparticles such as titanium dioxide have the potential to become transparent and are therefore widely used in cosmetic products and sunscreen. Research on the toxicity of nanoparticles is of utmost importance and numerous in vitro studies have shown that some of these particles could have adverse health effects. The current study aimed to investigate the in vivo effects of two different titanium nanoparticles at two different concentrations after inhalation by experimental BALB/c mice. This was done to determine whether these particles will cause an inflammatory reaction, visible as alterations in platelet and fibrin ultrastructure. Mice were divided into five experimental groups comprising of a control group, high and low concentration groups exposed to the spherical-shaped particles, as well as high and low concentration groups exposed to the rod-shaped particles. The ultrastructure of the fibrin networks and platelet aggregates of these experimental groups were investigated and compared to that of controls. Results indicated that the fibrin networks of the exposed animals have a net-like covering over the major fibres, typical to that found in animals with inflammation. It can therefore be concluded that the nanoparticles used in this study may have the potential to cause an inflammatory reaction, affecting the haemostatic physiology.

Las nanopartículas han sido diseñadas para realizar funciones específicas, y por lo tanto, tienen propiedades específicas que podrían ser perjudiciales. Las nanopartículas, como el dióxido de titanio tienen el potencial de llegar a ser transparentes, pudiendo ser ampliamente utilizadas en productos cosméticos y protectores solares. La investigación sobre la toxicidad de las nanopartículas es de suma importancia y numerosos estudios in vitro han demostrado que algunas de estas partículas, podrían tener efectos adversos para la salud. El presente estudio tuvo como objetivo investigar los efectos in vivo de dos nanopartículas de titanio diferentes en dos concentraciones después de la inhalación experimental de ratones BALB/c. Esto se realizó para determinar si las partículas provocan una reacción inflamatoria, visible como alteraciones en la ultraestructura de plaquetas y fibrina. Los ratones se dividieron en cinco grupos experimentales, que comprende un grupo control y grupos expuestos a nanopartículas de forma esférica de alta y baja concentración, así como grupos expuestos a nanopartículas en forma de barra de alta y baja concentración. Fueron investigadas la ultraestructura de las redes de fibrina y agregados plaquetarios de estos grupos experimentales y se comparó con la de los controles. Los resultados indicaron que en los animales expuestos se observó una red de fibrina que recubría las fibras más grandes, típicas de las que se encuentran en los animales con inflamación. Por lo tanto, puede concluirse que las nanopartículas utilizadas en este estudio pueden tener el potencial de causar una reacción inflamatoria, afectando a la fisiología hemostática.