Dose Of CdCl2 Research Articles

Cadmium-induced fetal erythropoiesis disturbances in mice

Maternal anemia has been identified as a contributing factor to adverse reproductive outcomes associated with cadmium (Cd) exposure, a common heavy metal. Our recent findings suggest that inhibited erythroid differentiation and enucleation also play significant roles in the direct embryonic toxicity resulting from maternal Cd exposure. However, the effects of Cd exposure on lipid metabolism remodeling, which is essential for physiological erythropoiesis, remain poorly understood. In the present study, pregnant mice were administered low doses of CdCl2 via oral exposure from early to late gestation to mitigate Cd-induced maternal anemia. Compared to vehicle-treated controls, embryos from Cd-treated mice exhibited a slight decrease in weight, though without signs of atrophy. Consistent with our previous observations, fetal livers from Cd-exposed embryos demonstrated a dose-dependent inhibition of erythroid differentiation, as confirmed by ex vivo analysis. Notably, an intrinsic decrease in lipid peroxidation during erythroid differentiation was observed in the bone marrow and fetal livers of vehicle-treated mice, attributed to diminished lipid content. In contrast, this decrease in lipid peroxidation was absent in fetal liver erythroblasts from Cd-treated mice, where an increase in lipid peroxidation was instead noted. These findings elucidate a potential mechanism, lipid peroxidation, underlying Cd-induced embryonic toxicity.

Cadmium causes spleen toxicity in chickens by regulating mitochondrial unfolded protein response and nuclear receptors response

Cadmium (Cd) is a heavy metal that pollutes the environment and threatens human and animal health via the food chain. The spleen is one of the target organs affected by Cd toxicity. However, the mechanism of Cd toxicity is not fully understood. In this study, 80 chicks were allocated into 4 groups (n = 20) and exposed to different doses of CdCl2 (0 mg/kg, 35 mg/kg, 70 mg/kg and 140 mg/kg) for 90 d. The pathological changes in the spleen, mitochondrial dynamics-related factors, cytochrome P450 (CYP450) enzyme system contents, activities, transcription levels, nuclear receptors (NRs) response molecule levels, and mitochondrial unfolded protein-related factors were detected. The findings indicate that exposure to Cd significantly leads to spleen injury. In Cd groups, the total contents of CYP450 and cytochrome b5 (Cyt b5) increased, and the activities of the CYP450 enzyme system (APND, ERND, AH, and NCR) changed. The NRs response was induced, and the gene levels of AHR/CAR and corresponding CYP450 isoforms (CYP1B1, CYP1A5, CYP1A1, CYP2C18, CYP2D6 and CYP3A4) were found altered. The study found that Cd exposure altered the mRNA expression levels of mitochondrial dynamics-related factors, such as OPA1, Fis1, MFF, Mfn1, and Mfn2, breaking mitochondrial fusion and cleavage and ultimately leading to mitochondrial dysfunction. Changes were detected in the gene levels of several mitochondrial unfolded protein response (mtUPR)-related factors, namely (SIRT1, PGC-1α, NRF1, TFAM, SOD2, and HtrA2). Cd also altered the gene levels of mitochondrial function-related factors (VDAC1, Cyt-C, COA6, PRDX3, RAF and SIRT3). It is showed that Cd can initiate the NRs response, influence the homeostasis of the CPY450 enzyme system, trigger the mtUPR, impair mitochondrial function, and ultimately lead to Cd toxicity in the spleen of chickens.

The Effects of Seleno-Methionine in Cadmium-Challenged Human Primary Chondrocytes.

Cadmium (Cd) is a potentially toxic element able to interfere with cellular functions and lead to disease or even death. Cd accumulation has been demonstrated in cartilage, where it can induce damage in joints. The aim of this study was to evaluate the effect of CdCl2 on primary cultures of human chondrocytes and the possible protective effect of seleno-methionine (Se-Met). Human primary articular chondrocytes were cultured and treated as follows: control groups, cells challenged with 7.5 μM and 10 μM CdCl2 alone, and cells pretreated with 10 and 20 μM Se-Met and then challenged with 7.5 μM and 10 μM CdCl2. Twenty-four hours after incubation, cell viability, histological evaluation with hematoxylin-eosin stain, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay were performed. Furthermore, reverse transcription-PCR was carried out to evaluate mRNA levels of BAX, BAK1, CASP-3, and CASP-9. After CdCl2 challenge at both doses, a reduced cell viability and an overexpression of BAX, BAK1, CASP-3, and CASP-9 genes, as well as a high number of TUNEL-positive cells, were demonstrated, all parameters becoming higher as the dose of CdCl2 was increased. The pretreatment with Se-Met lowered the expression of all considered genes, improved cell viability and morphological changes, and reduced the number of TUNEL-positive cells. It was concluded that Se-Met plays a protective role against CdCl2-induced structural and functional changes in chondrocytes in vitro, as it improved cell viability and showed a positive role in the context of the apoptotic pathways. It is therefore suggested that a translational, multifaceted approach, with plant-based diets, bioactive functional foods, nutraceuticals, micronutrients, and drugs, is possibly advisable in situations of environmental pollution caused by potentially toxic elements.

Anti-Toxic Principles from Musa Sapientum and Moringa Oleifera Ameliorated Skin Histo-Pathology, Decreased Lipid Peroxidation and Promoted Melatonin/TNF-Alpha/p53-Mediated Apoptosis in Cadmium Chloride-Induced Carcinogenesis in Rats

This study evaluated anticancer potentials of Musa sapientum (MS) and Moringa oleifera (MO) in cadmium chloride (CdCl2)-induced skin and liver carcinogenesis. Musa sapientum fraction-1 (MSF1) and Moringa oleifera fraction-6 (MOF6) were extracted from MS suckers and MO leaves, respectively, using column-chromatography methods. Forty-five adult male rats were randomly divided into 11 groups (n = 5). Cancer-induction was via single intraperitoneal administration of 1.25 mg/kg CdCl2. Groups 1 and 2 received physiological saline and CdCl2 dose, respectively. Groups 3–5 received CdCl2 dose on day 1 but were post-treated on days 15–56 with 15 mg/kg MOF6, 30 mg/kg MOF6 and 10 mg/kg MSF1, respectively. Group 6 received CdCl2dose on day 1 and were post-treated on days 15– 28 with doxorubicin + cisplatin doses. Groups 7–9 received MOF6 dose and MSF1 dose, respectively (days 1–56). Groups 10 and 11 received CdCl2dose on day 1 and were posttreated with 30 mg/kg MOF6 and 10 mg/kg MSF1, respectively (days 1–56). Doxorubicin and extracts doses were administered orally. Skin histo-pathology (haematoxylin and eosin), sera melatonin and tumour necrosis factor-alpha (TNFa) (enzyme linked immunosorbent assays [ELISA]) levels were evaluated. Malondialdehyde (thiobarbituric acid assay) and p53 (ELISA) levels were evaluated in liver homogenates. Data were statistically analysed using ANOVA at p ≤ 0.05. Results showed skin histo-alterations in Group 2, compared with normal skin histology in Groups 1 and 3–11. Statistical analyses showed significant downregulation of p53, non-significant downregulations of malondialdehyde and TNFa, and non-significant upregulation of melatonin in Groups 3–11 compared with Group 2. Overall, post-treatments with MOF6 and MSF1 exhibited possible anticancer potentials of these plants extracts via degrees of amelioration of CdCl2-induced skin histo-pathology and carcinogenesis.

Coenzyme Q10 mitigates cadmium cardiotoxicity by downregulating NF-κB/NLRP3 inflammasome axis and attenuating oxidative stress in mice

Coenzyme Q10 (CoQ10) occurs naturally in the body and possesses antioxidant and cardioprotective effects. Cardiotoxicity has emerged as a serious effect of the exposure to cadmium (Cd). This study investigated the curative potential of CoQ10 on Cd cardiotoxicity in mice, emphasizing the involvement of oxidative stress (OS) and NF-κB/NLRP3 inflammasome axis. Mice received a single intraperitoneal dose of CdCl2 (6.5 mg/kg) and a week after, CoQ10 (100 mg/kg) was supplemented daily for 14 days. Mice that received Cd exhibited cardiac injury manifested by the elevated circulating cardiac troponin T (cTnT), CK-MB, LDH and AST. The histopathological and ultrastructural investigations supported the biochemical findings of cardiotoxicity in Cd-exposed mice. Cd administration increased cardiac MDA, NO and 8-oxodG while suppressed GSH and antioxidant enzymes. CoQ10 decreased serum CK-MB, LDH, AST and cTnT, ameliorated histopathological and ultrastructural changes in the heart of mice, decreased cardiac MDA, NO, and 8-OHdG and improved antioxidants. CoQ10 downregulated NF-κB p65, NLRP3 inflammasome, IL-1β, MCP-1, JNK1, and TGF-β in the heart of Cd-administered mice. Moreover, in silico molecular docking revealed the binding potential between CoQ10 and NF-κB, ASC1 PYD domain, NLRP3 PYD domain, MCP-1, and JNK. In conclusion, CoQ10 ameliorated Cd cardiotoxicity by preventing OS and inflammation and modulating NF-κB/NLRP3 inflammasome axis in mice. Therefore, CoQ10 exhibits potent therapeutic benefits in safeguarding cardiac tissue from the harmful consequences of exposure to Cd.

Influence of Selected Heavy Metals on Cell Growth and Camphor Secretion in Achillea gypsicola Hub. Mor. In Vitro Cell Cultures

The use of abiotic and biotic elicitors for increasing the accumulation of pharmaceutical active ingredients in plant tissues has gained an increasing interest worldwide. This study was intented to provide promoting accumulation of camphor and phenolic compound using cadmium chloride (CdCl2) and silver nitrate (AgNO3) in cell culture of Achillea gypsicola. Growing cells from 8-day-old cultures were treated with three concentrations (5, 25 and 50 µM) of CdCl2 and AgNO3, along with the control. The quantification of camphor and phenolic compound were performed using Headspace-GC-MS and spectrophotometer, respectively. The content of camphor and phenolic compound, cell number and cell dry weight were significantly affected by increasing doses of AgNO3 and CdCl2. The highest significant change in camphor content was observed in cell treated with 25 µM CdCl2 and AgNO3 with a 6.88 and 6.32 fold increase, respectively. The application of 50 µM AgNO3 and CdCl2, however, resulted in a rapid decine in all attributes studied, implying that culture of A. gypsicola is susceptible to elicitation by high concentrations of these elicitors. In conclusion, using AgNO3 and CdCl2 elicitors in cultured tissues of A. gypsicola would be of great importance to enhanced production of desired bioactive compounds of medicinal importance.

The effect of immunotherapy on the state of the antioxidant system in radiation damage in rats

Immunotropic drugs (such as sera, blood plasma and immunoglobulins) have polyfunctional activity with anti-infectious, antitoxic, homeostasis-regulating properties. Based on this, we conducted the present study with the purpose to evaluate the therapeutic effect of anti-cadmium -anti-radiation serum (AARS) on the level of radiation-chemical damage. Modeling of experimental radiation-chemical damage was carried out by preliminary 4-time subcutaneous injection of cadmium chloride solution (CdCl2) at doses of 1/500 LD50, followed by radiation exposure of 90 outbred white rats at doses of 7.0 and 9.0 Gy (LD50 and LD100, respectively). It was found that a single subcutaneous injection of TDC at a dose of 25 mg/kg of live weight 24 hours after the combined radiation-toxic damage had a radioprotective and antitoxic effect, increasing the survival rate of animals affected by lethal doses of CdCl2 and γ-rays. Increase in the survival rate of animals treated with the test agent after exposure to two-factor damage was due to inhibition of the concentration of BFR-active toxic compounds and reciprocal increase in the synthesis of metallothioneins and SOD. Thus, the use of immunotropic agent of anti-cadmium anti-radiation serum (AARS) after exposure to two-factor combined radiation-chemical damage provided 90% survival rate by induction of increased formation of metallothioneins and SOD, inhibition of redox-cycled toxic radicals formation and neutralization of cadmium toxicity with the help of anti-cadmium antibodies.

Synthesized gold nanoparticles mediated by Crassocephalum rubens extract down-regulate KIM-1/NGAL genes and inhibit oxidative stress in cadmium-induced kidney damage in rats

Cadmium (Cd) exposure induces kidney damage by mediating oxidative stress and inflammation. In this study, the role of Crassocephalum rubens-gold nanoparticles (C. rubens-AuNPs) in down-regulating kidney injury molecules-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) genes and inhibiting oxidative stress in Cd-induced kidney damage in rats was investigated. Thirty male Wistar rats were distributed randomly into six groups (n = 5). Group I served as control, while groups II, III, IV, and V rats were administered with 20 mg/kg b.w. cadmium chloride (CdCl2) for five consecutive days. Groups III, IV, and V rats were treated, 24 h after the last dose of CdCl2, with silymarin, 5 mg/kg and 10 mg/kg C. rubens-AuNPs, respectively, for 14 days. Group VI rats received 10 mg/kg C. rubens-AuNPs only for 14 days. Animals were sacrificed 24 h after the last dose of the treatment. Biochemical parameters such as kidney function markers, biomarkers of nephrotoxicity, and oxidative stress markers were assayed. Results indicated that 20 mg/kg b.w. CdCl2 caused kidney damage, as evidenced by significant (p < 0.05) increase in the levels of serum urea and creatinine, malondialdehyde, reduced level of superoxide dismutase (SOD), and increased mRNA expression of the kidney injury biomarkers (KIM-1 and NGAL genes), when compared with the control. However, these changes were attenuated by both doses of C. rubens-AuNPs when compared with Cd-induced nephrotoxic rats. It can be suggested that C. rubens-AuNPs have the potential to ameliorate kidney damage induced by Cd via oxidative stress inhibition and down-regulation of KIM-1/NGAL genes.

Effects of a novel probiotic mixture on the modulation of brain and intestine Aquaporin-4 gene expression in rats exposed to Cadmium.

Cadmium (Cd) is a toxicant metal that risks human and animal health. Nowadays, the vital role of Aquaporin-4 (AQP-4) in brain and gut cell permeability has gathered too much attention to protecting against heavy metals. Studies have shown that heavy metals can harm the body due to oxidative stress. Probiotics are known for their health-beneficial effects and establish as dietary adjuncts mainly for their antioxidant properties. This study investigated the impact of a novel probiotic combination including Lactobacillus casei IBRC-M10783, Lactobacillus rhamnosus IBRC-M10782, and Lactobacillus helveticus TG-34 on the AQP-4 gene expression in CdCl2-induced Wistar rats. Rats were divided into three groups and received a specific dose of CdCl2 or probiotics. The AQP-4 expression level had estimated by Real-Time PCR in both the intestine and brain. These results showed a significant reduction in AQP-4 gene expression in the probiotic treatment group compared to the CdCl2 control group in the intestine and brain for the first time. Our research showed that consuming a probiotic mixture of L. casei, L. rhamnosus, and L. helveticus can reduce the expression of the aquaporin-4 gene in the brain and intestine of rats exposed to Cadmium, which can be promising in the field of aquaporin-4 regulation.

Salicylic Acid Priming Regulates Stomatal Conductance, Trichome Density and Improves Cadmium Stress Tolerance in Mentha arvensis L.

The application of phytohormones through seed priming could enhance quality of important medicinal and aromatic plants (MAPs) under heavy metal stress. We evaluated the potential of salicylic acid (SA) priming for overcoming the adverse effects of cadmium stress in Mentha arvensis L. plants. Suckers of plants were primed with SA before transplanting them into soil. At 30 days after transplanting, two doses (50 and 100 μm) of CdCl2 were applied to the soil. Both Cd treatments altered plant growth, photosynthetic pigments, leaf gas exchange attributes, and mineral nutrient contents. The 50 and 100 μm Cd treatments increased endogenous Cd content by 97.95 and 98.03%, electrolyte leakage (EL) by 34.21 and 44.38%, hydrogen peroxide (H2O2) by 34.71 and 55.80%, malondialdehyde (MDA) by 53.08 and 63.15%, and superoxide content (O2–•) by 24.07 and 38.43%, respectively. Cd triggered the up-regulation of antioxidant enzyme activities (superoxide dismutase, SOD; catalase, CAT; ascorbate peroxidase, APX; and glutathione reductase GR) and increased osmolyte biosynthesis and, interestingly, secondary metabolite (SM) accumulation. The presence of SA and Cd had an additive effect on these parameters. Nevertheless, plants primed with SA regulated stomatal conductance under Cd stress. SA priming to menthol mint plants under Cd stress overcome the effects of Cd stress while increasing SMs.

Cadmium-Tolerant Rhizospheric Bacteria of the C3/CAM Intermediate Semi-Halophytic Common Ice Plant (Mesembryanthemum crystallinum L.) Grown in Contaminated Soils.

The common ice plant, Mesembryanthemum crystallinum L., has recently been found as a good candidate for phytoremediation of heavy-metal polluted soils. This semi-halophyte is a C3/CAM (Crassulacean acid metabolism) intermediate plant capable of tolerating extreme levels of cadmium in the soil. The aim of the work was to obtain and characterize novel, Cd-tolerant microbial strains that populate the root zone of M. crystallinum performing different types of photosynthetic metabolism and growing in Cd-contaminated substrates. The plants exhibiting either C3 or CAM photosynthesis were treated for 8 days with different CdCl2 doses to obtain final Cd concentrations ranging from 0.82 to 818 mg⋅kg–1 of soil d.w. The CAM phase was induced by highly saline conditions. After treatment, eighteen bacterial and three yeast strains were isolated from the rhizosphere and, after preliminary Cd-resistance in vitro test, five bacterial strains were selected and identified with a molecular proteomics technique. Two strains of the species Providencia rettgeri (W6 and W7) were obtained from the C3 phase and three (one Paenibacillus glucanolyticus S7 and two Rhodococcus erythropolis strains: S4 and S10) from the CAM performing plants. The isolates were further tested for Cd-resistance (treatment with either 1 mM or 10 mM CdCl2) and salinity tolerance (0.5 M NaCl) in model liquid cultures (incubation for 14 days). Providencia rettgeri W7 culture remained fully viable at 1 mM Cd, whereas Rh. erythropolis S4 and S10 together with P. glucanolyticus S7 were found to be resistant to 10 mM Cd in the presence of 0.5 M NaCl. It is suggested that the high tolerance of the common ice plant toward cadmium may result from the synergic action of the plant together with the Cd/salt-resistant strains occurring within rhizospheral microbiota. Moreover, the isolated bacteria appear as promising robust microorganisms for biotechnological applications in bio- and phytoremediation projects.

Morphophysiological changes and reactive oxygen species metabolism inCorchorus olitoriusL. under different abiotic stresses

AbstractAbiotic stress has become an alarming issue for plant survival due to the constant changes in the environment. Abiotic stresses such as drought, salt, waterlogging, and heavy metals largely influence plant growth and development that finally reduce crop productivity. The present study was carried out to investigate the responses of jute (Corchorus olitoriuscv. O-9897) plant under different abiotic stresses. At 15th days after sowing plants were exposed to different abiotic stresses for various duration. Two doses of NaCl (200 and 400 mM) were applied to impose salt stress, while two doses of CdCl2(2 and 4 mM) were applied for cadmium (Cd) stress. Waterlogging stress was applied for 5 and 15 days. Whereas drought stress was imposed on plants for 10 and 15 days. Leaf relative water content, SPAD value, plant height, above ground fresh and dry weight, leaf area, and stem diameter decreased upon exposure to salt, water deficit, Cd, and waterlogging stresses. These abiotic stresses resulted in oxidative damage which was evident by the increased levels of lipid peroxidation, H2O2, and electrolyte leakage (EL) together with altered antioxidant enzymes activities and glyoxalase system which are crucial for plants to fight against oxidative damage. Both duration of waterlogging and drought stress drastically affected plant morphophysiology, whereasC. olitoriuscould tolerate moderate level of salt (200 mM NaCl) and Cd (2 mM CdCl2). So the present study reveals that abiotic stresses cause substantial damages to the morphophysiology and oxidative stress tolerance ofC. olitoriuswhere the higher doses of NaCl and CdCl2as well as the increased duration of waterlogging and drought resulted in more deleterious effect.

Protection of histomorphology of vital organs by methanolic seed extract of Nigella sativa against cadmium-induced tissue injuries in rats

Background: Chemical-induced organ injuries have been on a fast rise for decades and these injuries have become common causes of mortality and morbidity in the society. Edible plant materials with medicinal properties have been used for treating various diseases for many centuries in folk medicine. Recently, the role of food or medicinal plants in human health has received considerable attention. Traditional uses of N. sativa seed range from soothing wounds to remedying cough, eczema, diabetes, inflammation of the bronchi and tooth aches; and these point to substantial tissue effects.&#x0D; Objective: We investigated the protective effects of methanolic seed extract of Nigella sativa (MENS) against cadmium-induced histomorphological alterations in heart, kidney and liver tissues of albino rats.&#x0D; Methods: Twenty five (25) male albino rats, weighing (200±20g), were randomly grouped into five groups: A, B, C, D, and E. Group B (Negative Control) received intraperitoneal administration of cadmium chloride (CdCl2, 5mg/kg) only, group C received CdCl2 and low dose MENS (300mg/kg, oral), group D received CdCl2 and high dose MENS (600mg/kg, oral), and group E (Positive control) received CdCl2 and Vitamin C (200mg/kg, oral), for 14 days. Group A (Normal control) received no administration. Heart, kidney and liver were harvested for histopathological analyses.&#x0D; Results: Cadmium (CdCl2) induced significant histomorphological changes in the studied organs, and the heart was the most damaged of all the organs studied; however a significantly ameliorative effect by methanolic seed extracts was observed.&#x0D; Conclusion: Nigella sativa seed extract is potentially tissue-protective against harmful chemical toxins like cadmium.&#x0D;

Co-exposures of TiO2 nanoparticles and cadmium ions at non-lethal doses aggravates liver injury in mice with ConA-induced hepatitis

The wide applications of titanium dioxide nanoparticles (TNP) and ubiquitous cadmium (Cd) pollution increase the chances of their co-existence in the environment and also pose potential health risks to humans. However, toxicological understanding of effects of co-exposures of TNP and Cd to mammals is still lacking. In this study, non-lethal doses of TNP and CdCl2 were intravenously co-administered to healthy or Concanavalin A (ConA)-induced acute hepatitis mice. Co-exposures of TNP and CdCl2 increased the accumulation of Cd2+ in the liver of hepatitis mice, which was 1.42-fold higher than that of healthy mice. Co-exposures also caused liver damage only in hepatitis mice on the basis of histopathological and biochemical evidence. Further study showed that co-exposure upregulated hepatic oxidative stress, which further induced autophagy and apoptosis only in the liver of hepatitis mice. This finding underlines the potential toxicological consequences of co-exposures of TNP and CdCl2 in hepatitis sufferers.

ANALYSIS OF MT2A AND MT3 GENE EXPRESSION IN RAT'S LIVER AND KIDNEY IN RESPONSE TO CADMIUM CHLORIDE POISONING

The aim of this study was to investigate the expression of metallothionein genes in the liver and kidneys of rats with acute cadmium poisoning.Simulation of poisoning with cadmium chloride was carried out on white outbred female rats, divided into 4 groups depending on the dose of the injected toxicant. RNA samples isolated from rat liver and kidneys were used as research materials.The multiplicity of expression of the MT3 gene in the kidneys increased at the lowest dose of CdCl2 , which was used in this experiment (0.029 mg / kg); with increasing dosage, the expression level decreased, but not lower than the control values. Analysis of the expression of the same gene in the liver showed a tendency towards a decrease in the content of transcripts with increasing dose. The frequency of expression of the MT2A gene at higher doses of CdCl2 increased both in the liver and in the kidneys.In the present work, statistically significant dose-dependent changes in the expression multiplicity of metallothionein genes were detected 24 hours after CdCl2 administration. The revealed differences in the level of transcriptional activity of metallothionein genes require further investigation, since there are probably differences in the level of gene expression at earlier and later periods of toxicant action.

The protective effects of simvastatin in Cadmium-Induced preosteoblast injury through Nox4

Cadmium (Cd) has a direct toxic effect on bones. Statins such as simvastatin have protective effects on various diseases, including on tissue injury. The current study revealed the efficacy of simvastatin on Cd-induced preosteoblast injury. Preosteoblast MC3T3-E1 cells were incubated with various doses of CdCl2 for 12 h, 24 h and 48 h, and then the cell cytotoxicity was assessed using MTT assay and flow cytometry, respectively. The expression level of Nox4 was assessed by Western blot and qRT-PCR. The morphological appearance of MC3T3-E1 cells was observed under a microscope. Cells exposed to CdCl2 (5 µM) were further treated by simvastatin at various doses, subsequently cell viability, apoptosis and the expression of Nox4 were measured. Furthermore, to confirm the protective effects of simvastatin on Cd-induced pre-osteoblast injury, functional rescue assays were performed after corresponding cell treatment by simvastatin (10−8 M), CdCl2 (5 µM), and overexpression of Nox4. Expressions of cell apoptosis-related markers were measured by Western blot and qRT-PCR. The results revealed that CdCl2 caused MC3T3-E1 cell injury because the cell viability was decreased and the apoptosis was increased. Nox4 expression was up-regulated with the increase of CdCl2 concentrations. Simvastatin increased the cell viability, relieved the cell apoptosis and Nox4 expression previously increased by CdCl2. The effects of CdCl2 on MC3T3-E1 cells and Nox4 expression could be attenuated by simvastatin, and promoted by Nox4 overexpression. The current study found that simvastatin protects Cd-induced preosteoblast injury via Nox4, thus, it can be used as a potential drug for treating cadmium-induced bone injury.

Cadmium induces iron deficiency anemia through the suppression of iron transport in the duodenum

Cadmium (Cd) is an environmental contaminant that triggers toxic effects in various tissues such as the kidney, liver, and lung. Cd can also cause abnormal iron metabolism, leading to anemia. Iron homeostasis is regulated by intestinal absorption. However, whether Cd affects the iron absorption pathway is unclear. We aimed to elucidate the relationship between the intestinal iron transporter system and Cd-induced iron deficiency anemia. C57BL/6J female and male mice, 129/Sv female mice, and DBA/2 female mice were given a single oral dose of CdCl2 by gavage. After 3 or 24 h, Cd decreased serum iron concentrations and inhibited the expression of iron transport-related genes in the duodenum. In particular, Cd decreased the levels of divalent metal transporter 1 and ferroportin 1 in the duodenum. In addition, human colon carcinoma Caco-2 cells were treated with CdCl2. After 72 h, Cd decreased the expression of iron transport-related factors in Caco-2 cells with a pattern similar to that seen in the murine duodenum. These findings suggest that Cd inhibits iron absorption through direct suppression of iron transport in duodenal enterocytes and contributes to abnormal iron metabolism.

Nigella sativa Seed Protects Against Cadmium-induced Renal Toxicity in Rats

Background: Prevalence of chemical-induced renal injuries has been on a fast rise over the years and has become the leading cause of mortality and morbidity in the society, with environmental pollutants, heavy metals inclusive, seen as the causal agents. Recently, the role of medicinal foods in human health has gained considerable attention. Objective: We investigated the protective effects of methanolic extract of Nigella sativa (MENS) (Black seed) against cadmium-induced renal toxicity in albino rats. Methods: Twenty-five (25) male albino rats, weighing (150-170g), were randomly grouped into five groups: A-E. Group B (Negative Control) received intraperitoneal administration of cadmium chloride (CdCl2, 5mg/kg) only, group C received CdCl2 and low dose MENS (300mg/kg, oral), group D received CdCl2 and high dose MENS (600mg/kg, oral), group E (Positive control) received CdCl2 and Vitamin C (200mg/kg, oral), for 7 days. No treatment was administered to group A (Normal control). Renal injury was assessed by measuring serum levels of Na+, K+, creatinine and blood urea nitrogen (BUN) using standard methods. The kidneys were harvested for histopathological examination. Results: CdCl2 induced significant nephrotoxicity with marked elevation in the levels of biochemical markers of renal functions (p&lt;0.05 or p&lt;0.01); these were, however, ameliorated by a low dose of MENS. Histopathological examination of the kidney sections supported the biochemical findings. Conclusion: We conclude that Nigella sativa seed extract, at a low dose, is potentially nephroprotective against harmful chemical toxins such as cadmium.

Evaluation of Blood Oxidant/Antioxidant Changes and Testicular Toxicity after Subacute Exposure to Cadmium in Albino Rats: Therapeutic Effect of Nigella sativa Seed Extracts.

Cells and tissues of the body are prone to oxidative damage as a result of an increased level of reactive oxygen species and nitrogen radical beyond the detoxifying ability of the endogenous antioxidant system. This study aimed to evaluate the ameliorative effect of methanolic extracts of Nigella sativa (MENS) against cadmium-induced blood oxidative stress and testicular toxicity in albino rats. Twenty-five (25) male albino rats, weighing (200 ± 20g), were randomly grouped into five groups (A-E). Group B (Negative Control) received intraperitoneal administration of cadmium chloride (CdCl2, 5 mg/kg) only, group C received CdCl2 and low dose MENS (300 mg/kg, oral), group D received CdCl2 and high dose MENS (600 mg/kg, oral), group E (Positive control) received CdCl2 and Vitamin C (200 mg/kg, oral), for 14 days. No treatment was administered to group A (Normal control). The oxidative state of the blood was assessed by measuring the blood levels or activities of MDA, CAT, GSH and SOD; while testicular injury was assessed by measuring serum testosterone level using ELISA. The testes were harvested for histopathological examination. The results showed that cadmium induced a marked elevation in the level of MDA, and a decrease in SOD, CAT and GSH levels or activities (p<0.05 or p<0.01); but no significant alteration in the serum testosterone level was found (p>0.05); Histopathological studies on the testes showed that cadmium significantly induced testicular injury, which was however ameliorated by the seed extract of N. sativa. We conclude that N. sativa seed extract is potentially testiculoprotective and attenuates oxidative stress against harmful chemical toxins such as cadmium.

Cadmium elicits alterations in mitochondrial morphology and functionality in C3H10T1/2Cl8 mouse embryonic fibroblasts

BackgroundCadmium is a widespread carcinogen. We previously showed that the administration of low CdCl2 doses for 24 h to healthy C3H10T1/2Cl8 mouse embryonic fibroblast cell line at the beginning of Cell Transformation Assay (CTA), up regulates genes involved in metal scavenging and antioxidant defense, like metallothioneines, glutathione S-transferases and heat shock proteins. Still, although most cells thrive normally in the following weeks, malignancy is triggered by CdCl2 and leads to the appearance of foci of transformed cells at the end of the CTA. In this work we aim at elucidating the early metabolic deregulation induced by cadmium, underlying healthy cell transformation into malignant cells. MethodsRespiratory metabolism was investigated through Seahorse Agilent assays, while oxidative stress level was assessed through fluorescent probes; DNA damage was evaluated by Comet assay, and mitochondrial morphology was analyzed in confocal microscopy. ResultsResults show that the initial response to CdCl2 involves mitochondria rearrangement into a perinuclear network. However, SOD1 and SOD2 activities are inhibited, leading to increased superoxide anion level, which in turn causes DNA strand breaks. From the metabolic point of view, cells increase their glycolytic flux, while all extra NADH produced is still efficiently reoxidized by mitochondria. ConclusionsOur results confirm previously shown response against cadmium toxicity; new data about glycolytic increase and mitochondrial rearrangements suggest pathways leading to cell transformation. General significanceIn this work we exploit the widely used, well known CTA, which allows following healthy cells transformation into a malignant phenotype, to understand early events in cadmium-induced carcinogenesis.