Effect of cadmium chloride toxicity on olfactory mucosa / Efecto de la toxicidad del cloruro de cadmio en la mucosa olfativa

SUMMARY: Cadmium is a highly toxic metal and affects the respiratory mucosa. The aim of the study is to show the inflammation and degenerative effect of cadmium on the olfactory mucosa. In this study, eight-week-old Wistar rats with an average weight of 170-190 g were divided into two groups (control and experiment) with 20 animals in each group and used in the experiments. The rats in the experimental group were given 2 mg/kg/day powdered cadmium chloride dissolved in water intraperitoneally every day for two weeks. At the end of the experiment, the nasal cavity was completely removed with anesthesia. Concha nasalis superior was separated, fixed with zinc-Formalin solution and decalcified with 5 % EDTA (Ethylene-diaminetetraacetic acid). After routine histopathological procedure, APAF-1 antibody was used for expression of Hematoxylin-Eosin (HE) and immunohistochemistry. Histopathological examination revealed interruptions in the basement membrane structure due to cadmium and degenerative changes in stem cells, degeneration in sensory cells and pycnosis in nuclei, dilatation in blood vessels and increased inflammation in connective tissue. APAF-1 expression was found to increase in epithelial cells and olfactory glands (Bowman gland) cells. It has been thought that cadmium toxicity increases cell degeneration and inflammation in the olfactory mucosa and may significantly affect cell death and olfactory metabolism by inducing the pro-apoptotic process.

El cadmio es un metal altamente tóxico que afecta la mucosa respiratoria. El objetivo fue mostrar el efecto inflamatorio y degenerativo del cadmio sobre la mucosa olfativa. En este estudio, ratas Wistar de ocho semanas de edad con un peso promedio de 170-190 g se dividieron en dos grupos (control y experimental) con 20 animales en cada grupo. Las ratas del grupo experimental recibieron 2 mg/kg/día de cloruro de cadmio en polvo disuelto en agua por vía intraperitoneal todos los días durante dos semanas. En los animales se exirpó la cavidad nasal bajo anestesia. Se separó la concha nasal superior, se fijó con solución de zinc-Formalina y se descalcificó con EDTA (ácido etilendiaminotetraacético) al 5 %. Después del procedimiento histopatológico de rutina, Hematoxilina- Eosina (HE) e inmunohistoquímica, se utilizó el anticuerpo APAF-1. El examen histopatológico reveló interrupciones en la estructura de la membrana basal debido al cadmio y cambios degenerativos en las células madre, degeneración en las células sensoriales y picnosis en los núcleos, dilatación de los vasos sanguíneos y aumento de la inflamación en el tejido conjuntivo. Se encontró que la expresión de APAF-1 aumenta en las células epiteliales y en las células de las glándulas olfatorias (glándulas de Bowman). Se ha pensado que la toxicidad del cadmio aumenta la degeneración celular y la inflamación en la mucosa olfativa y puede afectar significativamente la muerte celular y el metabolismo olfativo al inducir el proceso proapoptótico.

Protective roles of Pyracantha fortuneana extract on acute renal toxicity induced by cadmium chloride in rats

Abstract Purpose: To investigate the protective roles of pyracantha fortune fruit extract (PFE) on acute renal toxicity induced by cadmium chloride (CdCl2) in rats. Methods: Rats were pretreated with PFE and consecutively injected with CdCl2 (6.5 mg/kg) for 5 days. Results: The concentration of Cd, kidney weight, malondialdehyde (MDA), and nitric oxide (NO) production were remarkably increased in CdCl2 group as well as the levels of plasma uric acid, urea, and creatinine (P < 0.001). However, the body weight and glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione peroxidase (GR) levels were markedly reduced by CdCl2 treatment (P < 0.001). Histological manifestations of renal tissue showed severely adverse changes. Moreover, CdCl2 treatment significantly decreased the B-cell lymphoma-2 (Bcl-2) expression while increased the Bcl-2-Associated X Protein (Bax), tumor necrosis factor-α (TNF-α) expression (P < 0.001). Additionally, the expression of Nrf2/Keap 1 related proteins Keap-1 gained a significant increase (P < 0.001), whereas the Nrf2, HO-1, γ-GCS, GSH-Px and NQO1 expression decreased by CdCl2 treatment (P < 0.05). These rats were pretreated with PFE to improve the changes caused by CdCl2 treatment. Conclusion: PFE could protect the kidney against acute renal toxicity induced by CdCl2.

Impairment of renal structure and function following heterogeneous chemical mixture exposure in rats.

Renal structural and functional alterations following an exposure to a heterogeneous chemical mixture (HCM) of phthalic acid di butyl ester, 1, 2–dichlorobenzene, cadmium chloride and chromium trioxide, administered through oral gavage in low doses (1/100 and 1/1000 of LD50 value of individual chemical) for 60 days, followed by withdrawal till 120 days resulted in significant rise in kidney lipid peroxidation and fall in the activities of enzymatic antioxidants. However, withdrawal of HCM treatment restored most of these altered parameters. Degenerative changes in the kidney included proximal convoluted tubules devoid of brush boarder with cytoplasmic blebbing, dissolution and sloughing of nuclei. Cortical glomeruli were also affected with epithelial disintegration, pyknosis of podocyte nuclei and mesengial cell hyperplasia. The morphological alterations recovered fully in the low dose compared to the high dose treatment group.

Cadmium chloride toxicity suppresses osteogenic potential of rat bone marrow mesenchymal stem cells through reducing cell viability and bone matrix mineralization.

Background and Objectives: Cadmium an environmental pollutant, exert several risks to human health. In this study we investigated the effect of cadmium chloride (CdCl 2 ) on Viability, morphology and bone Matrix Miniralization of Rat Bone Marrow Mesenchymal Stem Cells (rMSCs). Materials and Methods: rMSCs were cultured in DMEM containing 15% FBS and pen-strep. After 21 days of treatment with the selected doses of 750 and 2000 nM of CdCl 2 viability, colony forming unit, population doubling number, DAN breakage and the morphology of the cells were studied. Also to study the effects of CdCl2 on differentiation property, the morphology and bone matrix mineralization via estimation of intracellular calcium concentration and quantitative alizarin red were also evaluated in the cells using Hoechst, Acridine orange and Alizarin red staining. Data was analyzed using one-way ANOVA and Tukey ' s test and the means difference was considered significant at P<0.05. Results: The mean viability, colony forming unit, population doubling number and also the mean bone matrix mineralization of the rMSCs treated with CdCl 2 significantly reduced in a dose dependent manner. Nuclear fragmentation and cytoplasm shrinkage was also seen in the treated cells. Conclusion: CdCl 2 can reduce the viability and bone matrix mineralization of rMSCs even at low doses.

Cadmium affects viability of bone marrow mesenchymal stem cells through membrane impairment, intracellular calcium elevation and DNA breakage.

Background: Cadmium is an important heavy metal with occupational and environmental hazard. Cadmium toxicity results mainly in bone-related complication such as itai-itai disease. Mesenchymal stem cells of the bone marrow have the ability to differentiate to osteoblasts which ensure the well-being of the bone tissue. Thus the aim was to investigate the effect of cadmium on viability of rat bone marrow mesenchymal stem cells. Materials and Methods: The rat bone marrow mesenchymal stem cells were grown to confluency in DMEM medium supplemented with 15% fetal bovine serum and penicillin-streptomycin up to third passage. Then the cells were treated with 0, 5, 15, 25, 35, and 45 of CdCl 2 at 12, 24, 36, and 48 h, and their viability was investigated using trypan blue staining. In addition, after treatment with selected dose (15 and 45 μM) and time (24 and 48 h) the cell morphology, DNA damage and calcium content of the cells were evaluated. Data was analyzed using one and two-way ANOVA (Tukey test) and the P<0.05 was taken as the level of significant. Results: Cadmium chloride caused significant dose and time-dependent reduction of viability. In addition, morphological changes such as nuclear breakage and chromatin condensation, as well as cytoplasm shrinkage, were observed. The Comet assay showed a significant dose-dependent increase in DNA damage and also a significant increase in the intracellular levels of Ca 2+ was observed. Conclusion: Cadmium chloride is a toxic compound which might affect the well-being of bone tissue through affecting the mesenchymal stem cells.

Citotoxicidad del cadmio en hepatocitos de ratón albino y sus posibles implicaciones en ambientes tropicales / Cadmium citotoxicity in mice hepatocytes and implications on tropical environments

We analyzed phenotypic, structural and ultrastructural alterations induced by Cd+2 in hepatocytes extracted from Swiss Albino mice. Cadmium was given orally in watery solution of CdCl2 during 100 days at concentrations of 50 ppm, 100 ppm and 150 ppm. In controls, distilled water alone was used. The samples were processed with the paraffin inclusion and hematoxilin-eosin coloration techniques for light microscopy. For transmission electron microscopy we used the conventional technique. We found phenotypic (size and weight differences) and physiologic changes (muscular weakness, unrest); at the structural level we noticed loss of trabecular disposition and of lobulillar architecture, lymphocyte agglomeration, vacuolization, dilatation of sinusoid and central vein, among others. The ultrastructural study evidenced alterations coincident with those seen with light microscopy, which were accentuated with the increase of metal concentration: nucleolus with a high number of fibrillar centers (50 ppm); voluminous lipidic drops in the cytoplasm, loose endoplasmic rough reticulum, citoplasmatic vacuolization, altered lisosomes and peroxisomes (100 ppm); contracted nuclei with condensed cromatine, dilatation of intracellular space and mitochondria, and loss of fibrillar areas (150 ppm). Cadmium produces a toxic effect in the hepatic cells; the effect is more severe at higher concentration, leading to cellular necrosis.

Se realizó un análisis de las alteraciones fenotípicas, estructurales y ultraestructurales inducidas por Cd+2 en hepatocitos de ratón albino suizo. El metal fue suministrado vía oral en solución acuosa de CdCl2 durante 100 días a concentraciones de 50 ppm, 100 ppm y 150 ppm, en los controles la solución de cadmio fue sustituida por agua destilada. Las muestras fueron procesadas utilizando la técnica de inclusión en parafina y teñidas con hematoxilina- eosina para microscopía óptica y por la técnica convencional para microscopía electrónica de transmisión. Identificamos cambios fenotípicos (diferencias entre talla y peso) y fisiológicos (debilidad muscular e intranquilidad); a nivel histológico, pérdida de la disposición trabecular y de la arquitectura lobulillar, focos de aglomerados linfocíticos, vacuolización, dilatación de sinosoides y de la vena central. El estudio ultraestructural señala diversas alteraciones tales como: nucléolo con un elevado número de centros fibrilares (50 ppm); voluminosas gotas de lípidos en el citoplasma, retículo endoplasmático rugoso distendido, vacuolización citoplasmática, lisosomas y peroxisomas alterados (100 ppm); núcleos contraídos con cromatina condensada, dilatación en el espacio intracelular y áreas de pérdida mitocondrial y fibrilar (150 ppm). Sugerimos que el cadmio ejerce un efecto tóxico en las células hepáticas el cual se hace más severo con el aumento de la concentración, llevando a la necrosis celular.

Effect of spirulina and Liv-52 on cadmium induced toxicity in albino rats.

Oral administration of cadmium (6mg/kg body weight/day) as cadmium chloride (CdCl2) for 30 days resulted in a significant increase in thiobarbituric acid reactive substances (TBARS) level and a decrease in the levels of copper, zinc, iron, selenium, glutathione, superoxide dismutase, catalase, glutathione peroxidase when compared to normal control. Administration of either Liv-52 alone or in combination with spirulina produced a well pronounced protective effect in respect to these parameters in cadmium intoxicated rats. The protective effect of spirulina and Liv-52 in respect to biochemical changes were also confirmed by histopathological study in the liver and kidney sections.

Gonadosomatic and hepatosomatic indices of the freshwater fish Notopterus notopterus (Pallas) in response to some heavy metal exposure.

Area wise, the measurement of LC50 for pollutants is of great value in predicting the safe concentration dose of the contaminant in the environment on different aquatic species. The lethality of toxic substances including heavy metals to the aquatic organisms are usually assessed by following static bio-assay or continuous flow methods. The toxicity tests for mercuric chloride (HgCl2), cadmium chloride (CdCl2) and their mixture on Notopterus notopterus was determined by using 96h LC50 concentration on fish N. notopterus which indicated that cadmium chloride (CdCl2) was less toxic and mercuric chloride (HgCl2) was most highly toxic. The order of toxicity is mercuric chloride > mixture > cadmium chloride. On the basis of gonadosomatic index the reproductive cycle of N. notopterus can be categorised into immature, developing, maturing, mature, ripe and spent stages. Liver forms important organ of the body, which has a role in the ovarian development. On exposure to heavy metals at sublethal concentration both GSI (gonadosomatic index) and HSI (hepatosomatic index) are reduced.

The carcinogenic potential of cadmium in the palatal and gingival epithelium of rats: a morphologic and morphometric analysis

Cádmio (Cd) é um metal pesado que exerce uma variedade de efeitos tóxicos, crônicos e agudos, em organismos expostos. O objetivo deste estudo foi investigar o potencial carcinogênico do Cd no epitélio do palato e da gengiva de ratos Wistar. Dois grupos de animais foram estudados: grupo 1 que consistiu de 5 ratos expostos a cloreto de cádmio (CdCl2) em água de bebedouro (300 mg/L) por um período de 6 meses; grupo 2 que também consistiu de 5 ratos submetidos às mesmas condições dos animais do grupo 1, mas permaneceu livre de Cd por um período adicional de 6 meses. Dois outros grupos (C1 and C2) com o mesmo número de animais, entretanto não expostos ao CdCl2, foram usados como controle para o grupo 1 e 2, respectivamente. Todos os animais foram pesados antes e após o período experimental. Após terem sido sacrificados, os tecidos de interesse para o estudo foram fixados em formalina a 10 por cento, processados por meio de técnica histopatológica padrão, corados em HE, e analisados sob microscopia de luz, utilizando parâmetros cariométricos e estereológicos. Perda de peso, atrofia do epitélio da gengiva e do palato mole foram os principais achados deste estudo, e verificados apenas no grupo 1 (p < 0.05). Em conclusão, Cd não produziu efeito carcinogênico nos tecidos orais, nas condições experimentais empregadas neste estudo.

Renal morphometry of fetuses rats treated with cadmium

El cadmio es un metal pesado que se encuentra en la tierra, aire y alimentos. Está presente en forma coditiana todos los días de la vida y actualmente es catalogado como un tóxico, teratogénico y agente carcinogénico. El cadamio causa numerosas lesiones a los órganos humanos y animales. Este trabajo tiene como objetivo investigar los efectos tóxicos en fetos de ratas expuestas a tratamiento con cloruro de cadmio. 10 ratas pre¤adas fueron divididas en dos grupos. Cinco ratas recibieron por administración intraperitoneal 5 mg/Kg de cloruro de cadmio por peso corporal, durante 10 días de pre¤ez y otras cinco ratas recibieron bajo las mismas condiciones del otro grupo, una solución de cloruro de sodio al 0.85 por ciento . Los fetos fueron extraídos junto con las placentas y funículos umbilicales a los 20 días de pre¤ez. La administración del cloruro de cadmio causó una reducción significativa en los pesos de los fetos y placentas. La longitud del funículo umbilical fue más corta en el grupo experimental que en el grupo control. El estudio evaluó las alteraciones morfológicas causadas en los túbulos proximal, distal, contorneados y colectores renales como también en las células del glomérulo renal. La morfometría evidenció alteraciones significativas en los túbulos proximales y en las células glomerulares y, en menor grado, en los túbulos distales. El borde en cepillo de la membrana celular se observó muy sensible y se visualizaron algunas alteraciones. Los glomérulos se presentaron con edema y la cápsula del glomérulo fue también afectada.

Oxygen uptake and filtration rate as animal health biomarker in Lamellidens marginalis (Lamarck).

The freshwater bivalve, L. marginalis was experimentally exposed to 10 and 30 ppm concentrations of CdCl2 to examine filtration rate, oxygen uptake and glycogen level of liver and gills for health assessment for their reuse in the reclamation of cadmium intoxicated environments. In situ experiment was also performed for better appraisal of the filtration rate in the lake. Oxygen uptake in the treated group exceeded that of control by 15-22% during the early 24 hr after cadmium exposure, but followed an essential decline (23-30%) thereafter. The reduction of filtration rate ranged from 12-62% in laboratory to 83-85% in field trials. At the tissue level, glycogen content was reduced by 61-72% in liver and 52-63% in gill. In both tissues, glycogen content was inversely proportional to the cadmium contents of the animal. Critical appraisal of data suggests that the threshold values of cadmium in gill and liver were 50-80 microg/g dw for oxygen uptake and 50-60 microg/g for filtration rate because of marked reduction of these parameters beyond the values of cadmium. It is concluded that filtration rate, oxygen uptake of the freshwater bivalve, L. marginalis can be used as biomarker for animal health assessment and for possible reuse of the stock animals.

Impact of CdCl2 on biochemical changes in planaria, Dugesia bengalensis Kawakatsu.

Cadmium induces different anomalous behavioral changes with dose and time dependent mortality and change in the macromolecular patterns of D. bengalensis. Bio-accumulation of heavy metal in planarians could be used to detect the level of water pollution.