Cadmium-treated Group Research Articles

Cardioprotective Effect of Eugenol Against Cd-Induced Inflammation, Oxidative Stress, and Dyslipidemia in Male Rats: An In Vivo and Molecular Docking Study.

Cadmium, a highly toxic heavy metal, can cause severe damage to several vital organs including the kidney, liver, and brain. Many of the natural compounds found in aromatic plants have beneficial pharmacological properties. Eugenol is one such compound reported to have anti-inflammatory and antioxidant properties. The aim of this study is to investigate whether eugenol, a natural compound found in aromatic plants known for its anti-inflammatory and antioxidant properties, can mitigate the detrimental effects of cadmium exposure on cardiac inflammation, oxidative stress, and dyslipidemia. Male albino rats were subjected to randomization into four groups, each comprising six animals, to investigate the potential of eugenol in mitigating cadmium-induced toxicity. All groups received oral gavage treatment for 21days. Following the treatment regimen, cardiac tissue specimens were collected for analysis. The assessment of cardiac antioxidant status entailed the determination of enzymatic activities including catalase, SOD, GST, and GPx. Additionally, levels of lipid peroxidation, reduced glutathione, protein carbonyl oxidation, and thiol levels were quantified in the cardiac tissue samples. To evaluate cardiac damage, marker enzymes such as LDH and CK-MB were measured. Furthermore, the inflammatory response in the cardiac tissue induced by cadmium exposure was assessed through the quantification of NO, TNF-α, and IL-6 levels. Additionally, molecular docking and dynamics studies were conducted utilizing autodock and GLIDE methodologies. Cadmium administration markedly enhanced the activities of LDH and CK-MB, prominent cardiac markers. Furthermore, cadmium treatment also demonstrated a significant decrease in the reduced glutathione levels and antioxidant enzyme activities. Significant elevation of the inflammatory markers was also observed in the cadmium-treated group. Eugenol treatment effectively ameliorates cadmium-induced biochemical changes. This study underscores the potent anti-inflammatory and antioxidant attributes of eugenol. Co-administration of eugenol alongside cadmium exhibited remarkable protective efficacy against cadmium-induced cardio-toxicity. Eugenol demonstrated the capability to reinstate the cellular redox equilibrium of rats subjected to cadmium treatment to levels akin to those of the normal control group.

Analysis the mechanism of cadmium-induced cytotoxicity in mouse testicular mesenchymal cells with miRNA transcriptomic

To analyze the mechanism of cadmium-induced cytotoxicity in mouse testicular mesenchymal cells(TM3) with transcriptome sequencing and bioinformatics techniques. TM3 cells were selected as the cell model and divided into control group(no cadmium treatment) and cadmium-treated group(20 μmol/L CdCl_2). After 24 hours of administration, cells were harvested to extract total RNA, and then miRNA expression profiles were obtained by sequencing program after RNA quality detection. The fold change(FC) >2, P<0.05 was used as the standard to screen for differentially expressed miRNAs. The quantitative real-time polymerase chain reaction(qRT-PCR) was used to verify the differentially expressed miRNAs. Then, their target genes were predicted by miRanda software to construct miRNA-target gene interaction network, and their target genes were enriched by gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) pathway function. A total of 26 differentially expressed miRNAs were identified which may be related to cadmium-induced TM3 cytotoxicity, including 19 up-regulated and 7 down-regulated miRNAs. The result of qRT-PCR were consistent with the miRNA sequencing result. Meanwhile, bioinformatics analysis result showed that the 26 differentially expressed miRNAs predicted 657 target genes. GO enrichment was mainly classified into biological regulation, metabolic process, protein binding and catalytic activity. KEGG pathway analysis showed that target genes were significantly involved in mitogen-activated protein kinase(MAPK) and tumor necrosis factor(TNF) signal pathways closely related to inflammatory response and apoptosis. Cadmium can lead to the differential expression of miRNAs in TM3 cells, and its target genes may be involved in Cd-induced TM3 cytotoxicity through signaling pathways such as MAPK and TNF.

Effect of reactive oxygen species in cadmium chloride induced apoptosis of mouse Leydig cells

To study the effect of reactive oxygen species(ROS) in cadmium chloride-induced apoptosis of mouse Leydig cells(TM3 cells) and explore the underlying molecular mechanisms.TM3 cells were used as an in vitro model for studying reproductive toxicity induced by cadmium exposure. The cells were treated with different concentrations of CdCl_2(0, 5 and 10 μmol/L) for 24 h. CCK-8 assay was used to detect the effect of CdCl_2 on TM3 cell activity. Hoechst33342 staining was performed to explore the formation of apoptotic bodies. DCFH-DA probe was used to detect the level of ROS in the cells. TM3 cells were pretreated with 1 mmol/L NAC for 1 h and then treated with 10 μmol/L CdCl_2 for 24 h. The protein expression levels of pro-apoptotic proteins Caspase-9 and cleaved Caspase-3 were detected by Western blot; RT-qPCR was used to measure the expression of anti-apoptotic gene Bcl-2 and pro-apoptotic genes Caspase-9 and Caspase-3.After exposure to CdCl_2 for 24 h, viability of TM3 cells decreased and the number of apoptotic bodies increased. Western blot result showed that the protein level of Caspase-9 in the 10 μmol/L CdCl_2 treatment group was increased to 0.86±0.10(P<0.05) compared with the control group(0.56±0.07). Compared with the control group(0.37±0.11), the protein level of cleaved Caspase-3 in the 5 and 10 μmol/L CdCl_2 treatment groups were increased to 0.65±0.03 and 1.05±0.13(P<0.05). Compared with the control group(46.80±1.24), the intracellular ROS content in the 5 and 10 μmol/L treatment groups increased to 60.47±1.39 and 80.63±1.34(P<0.05). Compared with the cadmium-treated group, NAC inhibited Caspase-9(CdCl_2 group: 0.89±0.07; CdCl_2+NAC group: 0.28±0.02)and cleaved Caspase-3(CdCl_2 group: 1.53±0.21; CdCl_2+NAC group: 0.66 ±0.07), the difference was statistically significant(P<0.05). At the same time, NAC decreased the ROS level(62.64±0.93) in the CdCl_2 exposure group(80.13±0.94)(P<0.05). In addition, RT-qPCR result showed that the Caspase-9 mRNA levels in the 5 and 10 μmol/L CdCl_2 treatment groups were 1.40±0.14 and 1.90±0.12(P<0.05), compared with the control group(0.97±0.10). Compared with the control group(0.88±0.08), the cleaved Caspase-3 mRNA levels in the 5 and 10 μmol/L CdCl_2 treatment groups were increased to 1.42±0.11 and 1.59±0.12(P<0.05). While in the 5 and 10 μmol/L CdCl_2-treated group, compared with the control group(0.94±0.02), the Bcl-2 mRNA level were decreased to 0.60±0.02 and 0.50±0.09(P<0.05). Compared with the cadmium treatment group(0.57±0.06), NAC could significantly improve the cadmium-induced Bcl-2 mRNA expression level(0.92±0.03), and Caspase-9(CdCl_2 group: 1.96±0.07; CdCl_2+NAC group: 1.04±0.02) and Caspase-3(CdCl_2 group: 1.65±0.02; CdCl_2+NAC group: 0.66±0.04) were decreased(P<0.05).The Caspase cascade in mouse Leydig cells can be activated by excessive ROS induced by CdCl_2, and inhibition of ROS production can significantly reduce the CdCl_2-induced apoptosis of TM3 cells.

Effect of reactive oxygen species in cadmium chloride induced apoptosis of mouse Leydig cells

To study the effect of reactive oxygen species(ROS) in cadmium chloride-induced apoptosis of mouse Leydig cells(TM3 cells) and explore the underlying molecular mechanisms. TM3 cells were used as an in vitro model for studying reproductive toxicity induced by cadmium exposure. The cells were treated with different concentrations of CdCl_2(0, 5 and 10 μmol/L) for 24 h. CCK-8 assay was used to detect the effect of CdCl_2 on TM3 cell activity. Hoechst33342 staining was performed to explore the formation of apoptotic bodies. DCFH-DA probe was used to detect the level of ROS in the cells. TM3 cells were pretreated with 1 mmol/L NAC for 1 h and then treated with 10 μmol/L CdCl_2 for 24 h. The protein expression levels of pro-apoptotic proteins Caspase-9 and cleaved Caspase-3 were detected by Western blot; RT-qPCR was used to measure the expression of anti-apoptotic gene Bcl-2 and pro-apoptotic genes Caspase-9 and Caspase-3. After exposure to CdCl_2 for 24 h, viability of TM3 cells decreased and the number of apoptotic bodies increased. Western blot result showed that the protein level of Caspase-9 in the 10 μmol/L CdCl_2 treatment group was increased to 0.86±0.10(P<0.05) compared with the control group(0.56±0.07). Compared with the control group(0.37±0.11), the protein level of cleaved Caspase-3 in the 5 and 10 μmol/L CdCl_2 treatment groups were increased to 0.65±0.03 and 1.05±0.13(P<0.05). Compared with the control group(46.80±1.24), the intracellular ROS content in the 5 and 10 μmol/L treatment groups increased to 60.47±1.39 and 80.63±1.34(P<0.05). Compared with the cadmium-treated group, NAC inhibited Caspase-9(CdCl_2 group: 0.89±0.07; CdCl_2+NAC group: 0.28±0.02)and cleaved Caspase-3(CdCl_2 group: 1.53±0.21; CdCl_2+NAC group: 0.66 ±0.07), the difference was statistically significant(P<0.05). At the same time, NAC decreased the ROS level(62.64±0.93) in the CdCl_2 exposure group(80.13±0.94)(P<0.05). In addition, RT-qPCR result showed that the Caspase-9 mRNA levels in the 5 and 10 μmol/L CdCl_2 treatment groups were 1.40±0.14 and 1.90±0.12(P<0.05), compared with the control group(0.97±0.10). Compared with the control group(0.88±0.08), the cleaved Caspase-3 mRNA levels in the 5 and 10 μmol/L CdCl_2 treatment groups were increased to 1.42±0.11 and 1.59±0.12(P<0.05). While in the 5 and 10 μmol/L CdCl_2-treated group, compared with the control group(0.94±0.02), the Bcl-2 mRNA level were decreased to 0.60±0.02 and 0.50±0.09(P<0.05). Compared with the cadmium treatment group(0.57±0.06), NAC could significantly improve the cadmium-induced Bcl-2 mRNA expression level(0.92±0.03), and Caspase-9(CdCl_2 group: 1.96±0.07; CdCl_2+NAC group: 1.04±0.02) and Caspase-3(CdCl_2 group: 1.65±0.02; CdCl_2+NAC group: 0.66±0.04) were decreased(P<0.05). The Caspase cascade in mouse Leydig cells can be activated by excessive ROS induced by CdCl_2, and inhibition of ROS production can significantly reduce the CdCl_2-induced apoptosis of TM3 cells.

Therapeutic potential of Opuntia ficus indica extract against cadmium-induced osteoporosis and DNA bone damage in male rats

The purpose of the present study was to assess the protective effects of ‘Opuntia ficus indica’ (family Cactaceae) against osteoporosis induced by cadmium chloride in female Wistar rats. Experiments were carried out on 36 male Wistar rats (6-8 weeks old) divided into four groups of nine each: a control group, a group treated with cadmium (3,5 mg/kg /day) by subcutaneous injection, a group treated with Opuntia ficus indica extract (100 mg/Kg/day) by gavage, and a group treated with opuntia extract then treated with cadmium. After 10 weeks of treatment, animals from each group were rapidly sacri?ced by decapitation. Blood serum was obtained by centrifugation. Bone toxicity was estimated by examining femoral length and weight, calcium, phosphorus, vitamin D3 and alkaline phsphatase (ALP) levels, oxidative status and DNA aspects in femur tissue. Results showed that cadmium could induce hypocalcemia, hypophosphatemia, Vit D deficiency, increase in ALP level, and decrease in femur weight and length. Also, an oxidative stress evidenced by statistically signi?cant losses in the activities of catalase (CAT), superoxide-dismutase (SOD), glutathione-peroxidase (GPX) activities and an increase in lipids peroxidation level in bone tissue of cadmium-treated group compared with the control group. In addition, histological analysis in bone tissue of cadmium-induced rats revealed pronounced morphological alterations with areas of bone resorption and a loss of normal architecture of femur diaphysis bone as well as DNA fragmentation. However, administration of cactus extract attenuated cadmium-induced bone damage. The protective effect of the plant can be attributed to its antioxidant properties and the existence of phenolic acids and flavonoids, as highlighted by HPLC-based analysis. These findings indicate that ‘Opuntia ficus indica’ extract, can be used as a new option in nutraceutical field.
 

Ficus natalensis extract alleviates Cadmium chloride-induced testicular disruptions in albino rats

BackgroundCadmium is a potential environmental pollutant with worldwide health problems. Many Ficus species are reported to have an extensive diversity of traditional uses, among them the treatment of reproductive toxicity. ObjectivesThis study set out to evaluate the effect of Ficus natalensis extract on the testicular impairments induced by cadmium chloride (CdCl2) and investigated the potential mechanisms associated with its treatment. MethodsThus, 40 male albino rats were categorized into 4 groups (n = 10); group I (control), group II (cadmium-treated group) orally received 5 mg/kg/day CdCl2 for one month, group III (cadmium + Ficus natalensis extract) orally received 5 mg/kg/day CdCl2 for one month plus 200 mg/kg/day Ficus natalensis extract for another month, and group IV (cadmium + reference drug (mesterolone) orally received 5 mg/kg/day CdCl2 for one month plus 4.16 mg/kg/day mesterolone for another month. ResultsAt the end of experiment, CdCl2 administration markedly induced histological and histo-morphometric changes with a substantial (p < 0.05) decrease in the sperm count, sperm motility, serum TAC, serum testosterone, downregulation in the mRNA expression levels of testicular 17β-HSD and StAR, in addition to a significant increase in serum TNF-α and testicular MDA level compared to the control group. Conversely, the treatment with Ficus natalensis methanolic extract as well as the reference drug significantly ameliorated the above-mentioned adverse effects induced by CdCl2. ConclusionsOur results suggested that Ficus natalensis extract can attenuate the CdCl2-induced testicular impairments via inhibiting the oxidative cell damage and inflammation that contributed to CdCl2 toxicity.

Effect of Thymus vulgaris leaf extract on cadmium-induced testicular toxicity in rats

BackgroundCadmium (Cd) is a known metallohormone which mimics the action of steroid hormones with adverse effect on testicular function. It is highly toxic and a prevalent environmental contaminant with no conventional antidote. This study investigates the possible ameliorative effects of Thymus vulgaris extract on testicular toxicity induced by Cd in male rats.ResultsThe testicular and epididymal weights, serum concentration of follicle stimulating hormone, luteinizing hormone, and testosterone were significantly (p ≤ 0.05) lower in the cadmium-treated group compared to the control. Necrosis of germ cells of the seminiferous tubules was observed in the testicular tissues of the cadmium-treated group. Administration of extract showed mild but non-significant (p ≥ 0.05) protective effect on the cadmium-induced decrease in sex hormones and sperm count as well as oxidative stress and histological changes.ConclusionThymus vulgaris leaf extract had weak ameliorative effect on cadmium-induced testicular injury in rats but with promising antioxidant activity.

Nanocurcumin versus mesenchymal stem cells in ameliorating the deleterious effects in the cadmium‐induced testicular injury: A crosstalk between oxidative and apoptotic markers

Cadmium (Cd), a grave occupational pollutant, can result in; testicular damage. This study was designed to distinguish the potential effect of bone marrow-derived mesenchymal stem cells (BM-MSCs) versus that of curcumin nanoemulsion on Cd-induced testicular damage. Fifty adult male Sprague Dawley rats were distributed into five groups; control, sham control, Cd-treated, stem cell-treated and nanocurcumin-treated groups. Histological, immune histochemical; caspase 3 and proliferating cell nuclear antigen (PCNA) and CD 68, testosterone levels, nitric oxide, malondialdehyde (MDA)/glutathione (GSH) superoxide, dismutase (SOD), Western blot; B-cell lymphoma (Bcl-2), BCL2-Associated X Protein (BAX), BAX/Bcl-2 ratio and morphometry were done. Cadmium-treated group showed degenerated, detached seminiferous tubules, vacuolations and wide interstitial spaces containing fluid exudates. The same group revealed increased expression of BAX, BAX/Bcl-2 ratio, caspase 3, CD 68 and increased mean values of MDA, NO. Concomitantly, Cd has significant reduction in PCNA, Bcl-2 and sperm cell count when compared to control group. BM-MSCs- and nanocurcumin-treated groups revealed well-structured tubules and were perceived to expressively enhance the deleterious changes induced by Cd. The injurious changes on the testis induced by Cd were obviously improved when treated with either MSCs or nano-curcumin. BM-MSCs exerted more ameliorative changes.

The Biochemical and Histological Effect of Cadmium Chloride on the Pancreas of Adult Albino Rats and the Possible Protective Effect of Nigella Sativa Seeds

Aim: The current study evaluates the important role of Nigella Sativa against cadmium (Cd) induced toxic changes in pancreasof rats.Materials and Methods: Eighteen adult Wistar albino rats were divided into three equal groups. Control group, cadmiumtreated group that received 5 mg CdCl2/kg BW/day dissolved in water orally for three months, and cadmium with Nigellasativa (NS) group received a mixture of 1g/kg/day of aqueous suspension of Nigella sativa seeds powder and 5 mgCdCl2/kg BW/day dissolved in water for three consecutive months. Hormonal assay of insulin was done. Pancreatic tissueswere prepared for both Hematoxylin and Eosin and toluidine blue. Electron microscopic study of pancreatic tissues was alsodone.Results: The present study showed that the administration of CdCl2 induced evident decrease in insulin serum level. Thebiochemical results were confirmed by histological investigations where degenerative changes of pancreatic acini with lossof normal lobular architecture, distorted pancreatic acini, degenerated and widely separated cells in the islets of Langerhans,blood vessels congestion and aggregation of perivascular cellular infiltrates were detected in pancreatic tissues stained withH&E. Toluidine blue-stained sections showed few deeply stained apical zymogen granules in some acini, whereas other acinishowed absence of these granules.Administration of NS with CdCl2 showed a significant improvement in the measured serum insulin level and histologicalpictures.Conclusion: CdCl2 induced several toxic changes in the exocrine and endocrine parts of pancreas of rats. NS could protect thepancreas against these alterations.

The Effect of Crocin on Endocrine Functions of the Testes before and after Testicular Damage in Rats

AbstractAim of the Work: The aim of this work is to study the effect of crocin on endocrine functions of testes before and after testicular damage in rats.Methods: The present work will be carried on 40 male albino rats. The rats will be divided into four groups, (10 rats for each). Control group (group I): Rats received 1ml normal saline intraperitoneally. Cadmium-treated group (group II): Rats received intraperitoneal injection of a single dose of 1 mg/kg cadmium chloride dissolved in saline. Crocin-pretreated group (group III): Rats received crocin in a dose of 50mg/kg intra-peritoneally once daily for 4 weeks, then they received cadmium chloride as in group II. Crocin-treated group (group IV): Rats received cadmium chloride as in group II, then they treated with crocin as in group III. At the end of the experiment, the animals were anesthetized, then the animals were sacrificed by cervical decapitation. The collected blood samples were collected.Results: At the end of the experimental period, the results of the present work revealed that in Cd-treated group, there was significant decrease of serum levels of testosterone, FSH and LH. On the other hand, there was significant increase of testicular caspase-3 and testicular MDA with concomitant significant decrease of testicular GSH level compared to normal control group. In both the crocin-pretreated group and crocin-treated groups, there was significant increase of serum levels of testosterone, FSH and LH, significant decrease of testicular MDA levels associated with significant increase of testicular GSH levels as compared to cadmium-treated group. Testicular caspase-3 significanlty decreased in the crocin-treated group, but insignificanlty changed in crocin-pretreated as compared to cadmium-treated group. Also, all studied parameters significantly improved in crocin-treated group as compared to the crocin-pretreated group.Conclusion: We conclude that crocin can improve testicular toxicity induced by cadmium via its anti-apoptotic and anti-oxidant effects. Moreover, our results showed that the thera-peutic effect of crocin is more effective than its protective effect on testicular toxicity induced by Cd.

Probiotics as a Complementary Therapy in the Model of Cadmium Chloride Toxicity: Crosstalk of β-Catenin, BDNF, and StAR Signaling Pathways.

Cadmium chloride (CdCl2) is a ubiquitous environmental toxicant that causes a variety of disturbances in biological systems, including brain dysfunction and testicular tissue degeneration. On the other hand, it is supposed that beneficial properties of probiotic bacteria (Lactobacillus and Acidobacillus) are related to their capacity to adhere or bind different targets, thus leading to improved intestinal microbial balance and other benefits to the host. Bearing aforementioned in mind, the present study was undertaken to investigate the protective effect of probiotic supplementation against cadmium chloride-induced brain and testis toxicity in mice model. Animals received Lactobacillus and Acidobacillus either alone or added to folic acid for 1week before CdCl2 intoxication in a dose of 20mg/kg BW followed by probiotics (5 × 109) and/or folic acid (12mg/kg) treatment for 3weeks. The levels of malondialdehyde (MDA), butyrl choline esterase (BCHE), reduced glutathione (GSH), and total superoxide dismutase (SOD) activities were investigated. Finally, cadmium neurotoxicity was determined by estimating the gene expression of β-catenin and brain-derived neurotrophic factor (BDNF), as well as estimating the alterations in testicular function by determining acid phosphatase level in addition to steroidogenic acute regulatory protein (StAR) and 17-hydroxy steroid dehydrogenase (17-β HSD) gene expression. Based on our results, we can conclude that exposure of mice to cadmium chloride resulted in a significant elevation in MDA, BCHE levels accompanied with a significant reduction in GSH and SOD activities compared to the control value. CdCl2 also downregulated the gene expression of β-catenin and BDNF, as well as acid phosphatase level, in addition to StAR and 17-β HSD gene expression. These deviated parameters were significantly modulated in the co-treated animals with probiotics compared with the cadmium-treated group. In conclusion, Lactobacillus and folic acid in a mixture with cadmium acted beneficially to an organism, increasing the cadmium excretion in feces, and consequently increasing β-catenin and BDNF in brain tissue and StAR and 17-β HSD in testis and improving their functions. Histoarchitecture analysis confirmed these results.

Silymarin Ameliorates Oxidative Stress and Enhances Antioxidant Defense System Capacity in Cadmium-Treated Mice.

Objective Cadmium is an environmental pollutant which induces oxidative stress while silymarin as an antioxidant is able to scavenge free radicals. The aim of the present study was to investigate the effect of silymarin on oxidative stress markers and antioxidant defense system capacity in mice treated with cadmium chloride. Materials and Methods In this experimental study, adult mice were divided into four groups as follow: i. Control, ii. Cadmium chloride (5 mg/kg b.w., s.c.), iii. Silymarin+cadmium chloride, and iv. Silymarin (100 mg/kg b.w., i.p.). Mice were treated with cadmium chloride for 24 hours and silymarin was administered 24 hours before the cadmium. Blood samples were then collected from the experimental groups and their sera were prepared. To investigate oxidative stress markers in the serum, the amount of malondialdehyde (MDA) and thiol groups (-SH) were evaluated. To measure the total antioxidant power in the serum, Ferric Reducing/ Antioxidant Power (FRAP) method was used. In addition, the activity of enzymes including catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) was assessed to evaluate serum antioxidant defense power. Results In the cadmium-treated group, the amount of MDA significantly increased as compared to the control group. In silymarin+cadmium group, silymarin significantly ameliorated the level of MDA compared to the cadmium group. In addition, cadmium significantly reduced serum FRAP, the activity of antioxidant defense system enzymes and thiol groups compared to the control. In silymarin+cadmium group, silymarin could significantly reverse the reduction of these markers compared to the cadmium group. Administration of silymarin alone caused a significant increase in serum FRAP, the activity of antioxidant defense system enzymes and thiol groups compared to the control group. ConclusionSilymarin as a powerful antioxidant reverses the toxic effect of cadmium on the serum levels of lipid peroxidation, total antioxidant power, antioxidant defense system enzymes activity and thiol groups.

Protective effects of synbiotic diets of Bacillus coagulans, Lactobacillus plantarum and inulin against acute cadmium toxicity in rats

BackgroundCadmium is a heavy metal that causes oxidative stress and has toxic effects in humans. The aim of this study was to investigate the influence of two probiotics along with a prebiotic in preventing the toxic effects of cadmium in rats.MethodsTwenty-four male Wistar rats were randomly divided into four groups namely control, cadmium only, cadmium along with Lactobacillus plantarum (1 × 109 CFU/day) and inulin (5% of feedstuff) and cadmium along with Bacillus coagulans (1 × 109 spore/day) and inulin (5% of feedstuff). Cadmium treated groups received 200 μg/rat/day CdCl2 administered by gavage. During the 42-day experimental period, they were weighed weekly. For evaluation of changes in oxidative stress, the levels of some biochemicals and enzymes of serum including SOD, GPX, MDA, AST, ALT, total bilirubin, BUN and creatinine, and also SOD level of livers were measured at day 21 and 42 of treatment. The cadmium content of kidney and liver was determined by using atomic absorption mass spectrophotometry. Data were analyzed using analysis of variance (ANOVA) followed by Duncan’s post hoc test.ResultsTreatment of cadmium induced rats with synbiotic diets significantly improved the liver enzymes and biochemical parameters that decreased AST, ALT, total bilirubin, BUN and metal accumulation in the liver and kidney and increased body weight, serum and liver SOD values in comparison with the cadmium-treated group. No significant differences were observed with MDA and GPX values between all groups (p > 0.05).ConclusionsThis study showed that synbiotic diets containing probiotics (L. plantarum and B. coagulans) in combination with the prebiotic (inulin) can reduce the level of cadmium in the liver and kidney, preventing their damage and recover antioxidant enzymes in acute cadmium poisoning in rat.

Effects of cadmium exposure on medaka (&lt;i&gt;Oryzias latipes&lt;/i&gt;) testes

Adult male medaka (Oryzias latipes) were exposed to 10 ppm of cadmium for 96 h, and the testes were examined histopathologically. Numerous apoptotic cells were found in the spermatogonia and spermatocytes at 72 and 96 h after initiation of cadmium exposure, and the pyknotic index, TUNEL-positive rate, and cleaved caspase-3-positive rate in the spermatogonia and spermatocytes of the cadmium-treated group were higher compared with the control group. No significant difference between the control and cadmium-treated groups was found in the phospho-histone H3-positive rate in the spermatogonia and spermatocytes. No edematous, hemorrhagic, or necrotic changes were observed within the testes in the cadmium-treated group. These results suggest that spermatogonia and spermatocytes in medaka testes are highly sensitive to cadmium. Exposure to 10 ppm of cadmium induced histopathologic changes in the testes that were similar to those described in rodents exposed to low doses of cadmium.

Sulforaphane Prevents Testicular Damage in Kunming Mice Exposed to Cadmium via Activation of Nrf2/ARE Signaling Pathways.

Sulforaphane (SFN) is a natural and highly effective antioxidant. Studies suggest that SFN protects cells and tissues against cadmium (Cd) toxicity. This study investigated the protective effect of SFN against oxidative damage in the testes of Kunming mice exposed to cadmium, and explored the possible molecular mechanisms involved. Cadmium greatly reduced the serum testosterone levels in mice, reduced sperm motility, total sperm count, and increased the sperm deformity rate. Cadmium also reduces superoxide dismutase (T-SOD) and glutathione (GSH) levels and increases malondialdehyde (MDA) concentrations. SFN intervention improved sperm quality, serum testosterone, and antioxidant levels. Both mRNA and protein expression of mouse testicular nuclear factor-erythroid 2-related factor 2 (Nrf2) was reduced in cadmium-treated group. Furthermore, the downstream genes of Nrf2, glutathione peroxidase (GSH-Px), γ-glutamyl cysteine synthetase (γ-GCS), heme oxygenase-1 (HO-1), and NAD(P)H:quinone oxidoreductase-1 (NQO1) were also decreased in cadmium-treated group. SFN intervention increases the expression of these genes. Sulforaphane prevents cadmium-induced testicular damage, probably via activation of Nrf2/ARE signaling.

Genetic and Histopathological Responses to Cadmium Toxicity in Rabbit's Kidney and Liver: Protection by Ginger (Zingiber officinale).

This study aimed to examine the protective effects of ginger (G) on the genetic response induced by cadmium (Cd) and immunohistochemical expression of Caspase3 and MKI67 in the kidney and liver of rabbits. Male rabbits were divided into three groups; each group contains 10 animals: group (C) received basic diet and tap water for 12 weeks, the second group (Cd) received 200 mg/kg b.w CdCl2 in water for 12 weeks, group (Cd + G) was given 200 mg/kg b.w CdCl2 in water and 400 mg ginger/kg b.w in food for 12 weeks. Cd administration increased the activity of mRNA expression of the examined apoptotic (Caspase3), proliferation (MKI67), proto-oncogene (C-fos), and antioxidant (GST), while decreased the expression of anti-apoptotic (Bcl2). Ginger counteracted the effects of Cd in (Cd + G) group and downregulated the previously upregulated genes under Cd administration appeared in (Cd) group. The immunohistochemical expression of Caspase3 and MKI67 in the liver and kidney cells of the (C) group was shown very faint to negative reactions, strong staining in hepatocytes and the tubular epithelium in cadmium-treated group, while slight staining in some hepatocytes and tubular epithelium in co-administration with ginger in (Cd + G) group. In conclusion, ginger administration showed a protective effect against cadmium toxicity.

Cadmium‐induced microsatellite instability in the kidneys and leukocytes of C57BL/6J mice

Cadmium is a cytotoxic, carcinogenic, and mutagenic industrial product or byproduct. The correlation between metal exposure and microsatellite instability (MSI) has been reported by several groups. In the present study, 50 C57BL/6J mice at 6 weeks of age were divided into five groups and intraperitoneally injected with 0, 0.25, 0.5, 1, or 2 mg/kg cadmium chloride quaque die alterna for 4 weeks. Then, the liver, kidney, testis, leukocytes, bone marrow, and small intestine were collected from the treated mice and weighed. Portions of these tissues were fixed for further histological analysis, and the remaining tissues were subjected to genomic DNA extraction for the analysis of a panel of 42 microsatellite markers. The liver and testis weight coefficients were significantly changed in the 1 and 2 mg/kg cadmium chloride-treated groups compared with the control group. Simultaneously, severe histopathologic changes in the liver and kidneys, along with a complete disorganization of testicular structure and obvious severe necrosis in the testes were observed in the cadmium-treated group. The cadmium accumulated in the liver and kidneys of the mice in all cadmium-treated groups; the tissue cadmium concentrations were significantly higher than those in the control group. After STR scanning, MSI was found at three loci (D15Mit5, D10Mit266, and DxMit172) in the kidneys and leukocytes of mice in the lower dose groups (0.25 and 0.5 mg/kg). In summary, we have successfully established a sub-chronic cadmium exposure model and confirmed that cadmium exposure can induce MSI in mice. We also identified two loci that could be regarded as "hotspots" of microsatellite mutation in mice.

Effects of sub-chronic exposure to cadmium on some parameters of calcium and iodine metabolisms in the Shaw's jird Meriones shawi

In the present work we determined effects of a sub-chronic exposure to cadmium on some parameters of calcium and iodine metabolisms in Meriones shawi, a desert rodent species occupying the arid steppes of Tunisia and other countries. Fourteen jirds of both sex were equally divided into a control group receiving diet without cadmium and a treated group receiving cadmium in the diet during 30, 45, 60 and 90 days. At the end of each period, 5 jirds from each group were sacrificed. In cadmium-treated group, cadmium accumulation and total metallothioneins synthesis in the liver and kidneys were high and dependant on the duration of treatment. Cadmium caused significant modifications in the body weight and in the relative weights of the liver, femur and thyroids, in parallel to a decrease in calcium content in serum and in femur. Cadmium also decreased iodine content in serum and in the thyroids. Several impairments were dependant on the duration of exposure and were more pronounced at the end of the experiment. In conclusion, a sub-chronic exposure to cadmium induces perturbations in calcium and iodine metabolisms in Meriones shawi. However, effects on calcium seem to be more evident. We can conclude also that Meriones shawi is an indicator of cadmium presence in arid environments.

Biochemical and molecular effects of gestational and lactational coexposure to lead and cadmium on ovarian steroidogenesis are associated with oxidative stress in f1 generation rats

Few studies have characterized the molecular and biochemical mechanisms involved in ovarian steroidogenesis disruption by heavy metals, such as lead and cadmium coexposure, on F1 generation offspring. In this study, adult pregnant female rats were treated subcutaneously (0.05 mg/kg of body weight per day) with sodium acetate (control), lead acetate, and cadmium acetate separately and in combination throughout gestational and lactational period, and all animals from each of the experimental groups were sacrificed by decapitation on postnatal day 56 for various assays. The activities of key steroidogenic enzymes (17β-hydroxysteroid dehydrogenase and 3β-hydroxysteroid dehydrogenase) decreased in all the metal-treated groups. But the most significant decrease in the activities was observed in the cadmium-treated group, whereas the combined exposure group showed an intermediate effect. Serum estradiol and progesterone levels were also significantly altered in all the metal-treated groups, with the cadmium-exposed group showing maximum reductions as compared with the control group. The inhibitory effects of lead and cadmium on ovarian steroidogenic acute regulatory protein (StAR) mRNA levels along with CYP11 mRNA levels were also observed. Ovarian cholesterol content measured also showed significant depletion in all the metal-treated groups, with the cadmium-exposed group showing the maximum depletion. The activities of ovarian enzymatic antioxidants, such as superoxide dismutase, catalase, and glutathione peroxidase, were all significantly diminished along with significant depletion in nonenzymatic antioxidants. Lipid peroxidation was elevated significantly in all the metal-treated groups. In conclusion, lead and cadmium inhibit ovarian steroidogenesis by downregulating StAR gene expression along with inhibiting activities of steroidogenic enzymes and antioxidant system.

A Study on Characteristics of Atmospheric Heavy Metals in Subway Station

In this study, we investigated the atmospheric heavy metal concentrations in the particulate matter inside the subway stations of Seoul. In particular, we examined the correlation between the heavy metals and studied the effect of the heavy metals on cell proliferation. In six selected subway stations in Seoul, particulate matter was captured at the platforms and 11 types of heavy metals were analyzed. The results showed that the mean concentration of iron was the highest out of the heavy metals in particulate matter, followed by copper, potassium, calcium, zinc, nickel, sodium, manganese, magnesium, chromium and cadmium in that order. The correlation analysis showed that the correlations between the heavy metals was highest in the following order: (Cu vs Zn) , (Ca vs Na) , (Ca vs Mn) , (Ni vs Cr) , (Na vs Mn) , (Cr vs Cd) , (Zn vs Cd) , (Cu vs Cd) , (Ni vs Cd) , (Cu vs Ni) , (K vs Zn) , (Cu vs K) , (Cu vs Cr) , (K vs Cd) , (Zn vs Cr) , (K vs Ni) , (Zn vs Ni) , (K vs Cr) , and (Fe vs Cu) . The correlation coefficient between zinc and copper was 0.937, indicating the highest correlation. Copper, zinc, nickel, chromium and cadmium, which are generated from artificial sources in general, showed correlations with many of the other metals and the correlation coefficients were also relatively high. The effect of the heavy metals on cell proliferation was also investigated in this study. Cultured cell was exposed to 10 mg/l or 100 mg/l of iron, copper, calcium, zinc, nickel, manganese, magnesium, chromium and cadmium for 24 hours. The cell proliferation in all the heavy metal-treated groups was not inhibited at 10 mg/l of the heavy metal concentration. The only exception to this was with the cadmium-treated group which showed a strong cell proliferation inhibition. This study provides the fundamental data for the understanding of simultaneous heavy metal exposure tendency at the time of particulate matter exposure in subway stations and the identification of heavy metal sources. Moreover, this study can be used as the fundamental data for the cell toxicity study of the subway-oriented heavy metal-containing particulate matter.