Exposure To Cadmium Chloride Research Articles

Mitochondrial dysfunction-associated alveolar epithelial senescence is involved in CdCl2-induced COPD-like lung injury

An earlier study found that respiratory cadmium chloride (CdCl2) exposure caused COPD-like lung injury. This study aimed to explore whether mitochondrial dysfunction-mediated alveolar epithelial senescence is involved in CdCl2-induced COPD-like lung injury. Adult C57BL/6 mice were exposed to CdCl2 (10 mg/L) aerosol for six months. Beta-galactosidase-positive cells, p21 and p16 were increased in CdCl2-exposed mouse lungs. The in vitro experiments showed that γ-H2AX was elevated in CdCl2-exposed alveolar epithelial cells. The cGAS-STING pathway was activated in CdCl2-exposed alveolar epithelial cells and mouse lungs. Cxcl1, Cxcl9, Il-10, Il-1β and Mmp2, several senescence-associated secretory phenotypes (SASP), were upregulated in CdCl2-exposed alveolar epithelial cells. Mechanistically, CdCl2 exposure caused SIRT3 reduction and mitochondrial dysfunction in mouse lungs and alveolar epithelial cells. The in vitro experiment found that Sirt3 overexpression attenuated CdCl2-induced alveolar epithelial senescence and SASP. The in vivo experiments showed that Sirt3 gene knockout exacerbated CdCl2-induced alveolar epithelial senescence, alveolar structure damage, airway inflammation and pulmonary function decline. NMN, an NAD+ precursor, attenuated CdCl2-induced alveolar epithelial senescence and SASP in mouse lungs. Moreover, NMN supplementation prevented CdCl2-induced COPD-like alveolar structure damage, epithelial-mesenchymal transition and pulmonary function decline. These results suggest that mitochondrial dysfunction-associated alveolar epithelial senescence is involved in CdCl2-induced COPD-like lung injury.

Assessment of acute impacts of cadmium chloride exposure on blood sugar level, body and organs weight in male albino Wistar rats and the ameliorative effects of ethanol leaf extracts of Tapinanthus bangwensis and Mangifera indica

Impacts of acute cadmium chloride exposure on blood sugar level, body and organs weights in male albino Wistar rats and the ameliorative effects of ethanol leaf extracts of Tapinanthus bangwensis and Mangifera indica were assessed. Twenty –five animals (125- 285 g) were randomly assigned five groups of five rats each. Groups 1-4 were orally administered with cadmium chloride (30%) below its LD50 each for three times at 2days interval before treatment with the plant extracts. Groups 1 and 2 were later treated with 300 mg/kg of T. bangwensis and M. indica respectively. Group3 were treated with 300 mg/kg of both extracts at 50:50 dosage ratio. Groups 4 and 5 were not treated and they served as negative and normal control respectively. Treatment was done via oral route for 14 days and all animals were allowed free access to commercial rat mash and water. Blood sugar and body weight were assessed at 2days interval after exposing animals to the heavy metal followed by treatment. Organs weights were taken after 14days treatment. The results of the blood sugar level revealed significant increase (P< 0.05) in group 4 (untreated) when compared to the normal control group and the groups treated with leaf extracts. Significant decrease was recorded in body weight of the untreated rats when compared to the treated and normal groups. There was significant decrease (P< 0.05) in the weight of testis and liver in group 4 when compared to groups 1,2,3 and 5, with significant decrease (P< 0.05) in the weight of the kidneys in group 1 when compared to groups 3 and 5. These results implied that cadmium chloride toxicity altered blood sugar levels, body and organs weights in the animals, however, the two plant extracts ameliorated these impacts and regulated the parameters to fall within their normal ranges.

Impact of Cadmium Chloride (CdCl2) Exposure on Glucose Levels in Various Tissues of Heteropneustes fossilis

The present study examines the implications of acute and sub-acute exposure to cadmium chloride (CdCl2) on tissue specific glucose metabolism in muscle, gill, liver, heart, and kidney, after 30 and 60 days. Data represent significant increase in tissue glucose levels, corresponding to the metabolic response caused by cadmium-induced stress. We found out the glucose level after that 24 hour in the liver where the liver had the highest glucose levels, that the liver was going through its detox phase. Our results support a model in which there are systemic metabolic adaptations to cadmium toxicity having broader implications for how the metabolic response to exposure of an environmental toxicant is seen.

The involvement of SigmaR1K142 degradation mediated by ERAD in neural senescence linked with CdCl2 exposure

Alzheimer’s disease (AD) is the most common cause of dementia worldwide. Due to its uncertain pathogenesis, there is currently no treatment available for AD. Increasing evidences have linked cellular senescence to AD, although the mechanism triggering cellular senescence in AD requires further exploration. To investigate the involvement of cellular senescence in AD, we explored the effects of cadmium chloride (CdCl2) exposure, one of the potential environmental risk factors for AD, on neuron senescence in vivo and in vitro. β-amyloid (Aβ) and tubulin-associated protein (tau) pathologies were found to be enhanced by CdCl2 exposure in the in vitro models, while p53/p21/Rb cascade-related neuronal senescence pathways were activated. Conversely, the use of melatonin, a cellular senescence inhibitor, or a cadmium ion chelator suppressed CdCl2-induced neuron senescence, along with the Aβ and tau pathologies. Mechanistically, CdCl2 exposure activated the suppressor enhancer Lin-12/Notch 1-like (SEL1L)/HMG-CoA reductase degradation 1 (HRD1)-regulated endoplasmic reticulum-associated degradation (ERAD), which enhanced the ubiquitin degradation of sigma-1 receptor (SigmaR1) by specifically recognizing its K142 site, resulting in the activation of the p53/p21/Rb pathway via the induction of Ca2+ dyshomeostasis and mitochondrial dysfunction. In the in vivo models, the administration of the SigmaR1 agonist ANAVEX2–73 rescues neurobehavioral inhibition and alleviates cellular senescence and AD-like pathology in the brain tissue of CdCl2-exposed mice. Consequently, the present study revealed a novel senescence-associated regulatory route for the SEL1L/HRD1/SigmaR1 axis that affects the pathological progression of CdCl2 exposure-associated AD. CdCl2 exposure activated SEL1L/HRD1-mediated ERAD and promoted the ubiquitinated degradation of SigmaR1, activating p53/p21/Rb pathway-regulated neuronal senescence. The results of the present study suggest that SigmaR1 may function as a neuroprotective biomarker of neuronal senescence, and pharmacological activation of SigmaR1 could be a promising intervention strategy for AD therapy.

Caffeic acid attenuates memory dysfunction and restores the altered activity of cholinergic, monoaminergic and purinergic in brain of cadmium chloride exposure rats.

This study aims to evaluate the neuroprotective effect of caffeic acid (CAF) against cadmium chloride (CdCl2) in rats via its effect on memory index as well as on altered enzymatic activity in the brain of CdCl2-induced neurotoxicity. The experimental rats were divided into seven groups (n=6 rats per group) of healthy rats (group 1), CdCl2 -induced (CD) (3 mg/kg BW) rats (group 2), CD rats + Vitamin C (group 3), CD rats + CAF (10 and 20 mg/kg BW respectively) (group 4 & 5), and healthy rat + CAF (10 and 20 mg/kg BW respectively) (group 6 & 7). Thereafter, CdCl2 and CAF were administered orally to the experimental rats in group 2 to group 5 on daily basis for 14days. Then, the Y-maze test was performed on theexperimental rats to ascertain their memory index. CdCl2 administration significantly altered cognitive function, the activity of cholinesterase, monoamine oxidase, arginase, purinergic enzymes, nitric oxide (NOx), and antioxidant status of Cd rats (untreated) when compared with healthy rats. Thereafter, CD rats treated with vitamin C and CAF (10 and 20 mg/kg BW) respectively exhibited an improved cognitive function, and the observed altered activity of cholinesterase, monoamine oxidase, arginase, purinergic were restored when compared with untreated CD rats. Also, the level of brain NOx and antioxidant status were significantly (p<0.05) enhanced when compared with untreated CD rats. In the same vein, CAF administration offers neuro-protective effect in healthy ratsvis-à-vis improved cognitive function, reduction in the activity of some enzymes linked to the progression of cognitive dysfunction, and improved antioxidant status when compared to healthy rats devoid of CAF. This study demonstrated the neuroprotective effect of CAF against CdCl2 exposure and in healthy rats.

ANALYSIS OF CHRONIC EFFECTS OF CADMIUM CHLORIDE ON NEPHROGENESIS IN RATS

Basic clinical, morphological and statistical studies identify cadmium as one of the causes of toxic kidney damage and a number of diseases that overcomes the placental barrier. Determining the changes that occur in the morphology of organs under the impact of cadmium chloride in pregnant female rats is an urgent task for modern morphological research.&#x0D; Objectives. In this work, we investigate the nephrotoxic effects of chronic cadmium chloride exposure in pregnant rats in experiment. Material and methods. Pregnant rats with confirmed gestational age were administered a 2.0 mg/kg cadmium chloride solution daily via intragastric gavage. Surgical removal of the kidneys was performed on days 13 and 19 of gestation for subsequent analysis. We determined the kidney mass and assessed nephron elements on histological preparations. These measurements included the diameter of the renal corpuscle, the nephron capsule area, the glomerulus area, and their ratio (glomerulus area index).&#x0D; Results and discussion. Chronic exposure to cadmium chloride in a dose of 2.0 mg/kg reduced the weight of the kidneys in pregnant females at both periods of the study. At the histological level, an increase of the nephron capsule was found in combination with fragmentary sclerosis of glomerular capillaries that indicates the nephrotoxic effect of cadmium chloride in the indicated dose in the experiment on rats. The nephron area index of the kidneys of female rats with chronic exposure to cadmium had a pronounced tendency to decrease the area of the nephron capsule with a significant difference (p&lt;0.001) at both time points.&#x0D; Conclusion. Chronic cadmium chloride exposure resulted in reduced kidney weight in females. Histological examination revealed enlarged nephron capsules alongside glomerular capillary sclerosis, indicating the nephrotoxic effect of the administered dose in this rat experiment. Notably, the nephron area index displayed a consistent decline in the area of the nephron capsule at both time points in cadmium-exposed female ras.

Neurotoxic effects of cadmium chloride exposure combined with physical activity and protective effect of bioprophylactic agents

Introduction. Chemical compounds possessing of a neurotropic effect are extremely widespread in industry, which makes the problem of neurotoxicity relevant for occupational medicine. Since industrial workers are often exposed to a combination of both physical and chemical work-related risk factors, a complex adverse health effect of the latter should be considered.&#x0D; Our objective was to study neurotoxic effects of exposure to cadmium chloride combined with physical activity in a subchronic experiment on rats and assess the efficacy of a biological prophylactic complex.&#x0D; Material and methods. For six weeks, 0.77 mg/kg b.w. of cadmium chloride was intraperineally instilled to outbred male albino rats thrice a week. Five times a week, the rodents were forced to run for 10 minutes at a speed of 25 m/min. During the entire exposure period, half of the animals received a specially developed bioprophylactic complex consisting of pectin, monosodium glutamate, and a multivitamin/multimineral supplement with feed and drink.&#x0D; Results. In combination with physical activity, cadmium exposure caused depression, anxiety, low exploratory behaviour, and spatial memory disturbances. The developed bioprophylactic complex helped mitigate toxic effects of cadmium aggravated with intense physical activity and improve the general condition of the rodents.&#x0D; Limitations. The experiment was limited to examining the behaviour of male rats following subchronic exposure to a single dose of cadmium.&#x0D; Conclusions. Subchronic exposure to cadmium combined with physical activity can induce certain neurotoxic effects. Administration of the specially developed complex of biological protectors has shown to attenuate or minimize these effects. Similar measures can be taken to diminish risks of adverse health consequences of the factors studied.

In vitro cadmium exposure induces structural damage and endothelial dysfunction in female rat aorta.

Cadmium is a heavy metal that is widespread in the environment and has been described as a metalloestrogen and a cardiovascular risk factor. Experimental studies conducted in male animals have shown that cadmium exposure induces vascular dysfunction, which could lead to vasculopathies caused by this metal. However, it is necessary to investigate the vascular effects of cadmium in female rats to understand its potential sex-dependent impact on the cardiovascular system. While its effects on male rats have been studied, cadmium may act differently in females due to its potential as a metalloestrogen. In vitro studies conducted in a controlled environment allow for a direct assessment of cadmium's impact on vascular function, and the use of female rats ensures that sex-dependent effects are evaluated. Therefore, the aim of this study was to investigate the in vitro effects of Cadmium Chloride (CdCl2, 5µM) exposure on vascular reactivity in the isolated aorta of female Wistar rats. Exposure to CdCl2 damaged the architecture of the vascular endothelium. CdCl2 incubation increased the production and release of O2•-, reduced the participation of potassium (K+) channels, and increased the participation of the angiotensin II pathway in response to phenylephrine. Moreover, estrogen receptors alpha (Erα) modulated vascular reactivity to phenylephrine in the presence of cadmium, supporting the hypothesis that cadmium could act as a metalloestrogen. Our results demonstrated that in vitro cadmium exposure induces damage to endothelial architecture and an increase in oxidative stress in the isolated aorta of female rats, which could precipitate vasculopathies. Graphical Abstract. Own source from Canva and Servier Medical Art servers.

STRESS RELATED HISTOPATHOLOGICAL CHANGES IN THE HEPATOPANCREAS OF BOTH THE SEXES OF PALAEMONID PRAWN MACROBRACHIUM DAYANUM (HENDERSON) (CRUSTACEA : DECAPODA)

The palaemonid prawns Macrobrachium dayanum(Crustacea: Decapoda) are importantspecies found in river Gomti and are very good bioindicators. These prawns are ideal animals tostudy the histopathological impairments caused by the effect of heavy metals prominent in riverGomti. The test animals were exposed to LC50value (0.15 mg/l and 0.16 mg/l respectively)at acuteexposure for 24, 48,72 and 96h and at subacute exposure25% of 96hr LC50 values of CdCl2 for malesand females (0.0375mg/l &amp; 0.04 mg/l) respectively for 10, 20 and 30 day exposure. Thehistopathological changes were studied in both the sexes in the animals.Marked histopathologicalchanges were noticed in hepatopancreas of M.dayanum after cadmium chloride exposure. At 96 hacute exposure, hepatopancreas showed vacuolization in epithelial cells, necrosis in tunica propria,increased number of migratory cells, granuloma in intertubular connective tissue alongwithkaryorrhexis and karyolysis in cells. Necrotic and degenerative changes in hepatopancreaticepithelium, which were mainly, noticed in R and B cells. Loss of histological architecture along withthe heavy influx of haemocytes was recorded at this stage. After sub-acute exposure large vacuoles,particularly R and B cells were observed along with hypertrophy, necrosis and degenerative changesat most of the places in hepatopancreatic epithelium. Karyorrhexis and pyknosis were common.Increased number of migratory cells in intertubular spaces was a peculiar feature at this stage. Almostcomplete loss of the architecture of hepatopancreas was noticed and about 90 % of thehepatopancreatic tubules were found non–fuctional. The histopathological alteration in males wasmore pronounced than in females, both at acute and sub-acute exposure.

Cadmium chloride exposure impairs the growth and behavior of Drosophila via ferroptosis

Cadmium (Cd) is a widely distributed toxic heavy metal that enters the environment via anthropogenic mobilization and accumulates in plants and animals, causing metabolic abnormalities even mortality. Although the toxic effects and stress damage of cadmium have been investigated extensively over the past few decades, research on its ability to trigger ferroptosis, growth retardation, and behavioral abnormalities is insufficient. As a result, the effects of CdCl2 exposure on growth and development, activity and sleep, and ferroptosis in this study were examined in fruit fly (Drosophila melanogaster). When exposed to 0.5 mM CdCl2, the entire growth period from larvae to adults was prolonged, and the rates of pupation and eclosion were decreased. Additionally, CdCl2 exposure resulted in a decrease in body weight and individual size of fruit fly and high lethality rate. Moreover, CdCl2 exposure altered fruit fly behavior, including decreased activity and increased sleep duration, particularly in females. Ferrostatin-1 (Fer-1) is a potent selective ferroptosis inhibitor that effectively slows lipid hydroperoxide accumulation to rescue body size reduction and restore activity and sleep in CdCl2-exposed female flies. CdCl2 exposure could induce ferroptosis in fruit fly mechanistically, as evidenced by inhibition of Nrf2 signaling pathway, accumulation of lipid peroxidation, impairment of GPX4 antioxidant system, and upregulation of iron metabolism. Our findings suggest that Cd exposure triggers ferroptosis, which leads to growth retardation and behavioral disorders in fruit fly.

Toxicity of cadmium salts on indicators of embryogenesis of rats

Cadmium is a toxic heavy metal which is considered a dangerous environmental pollutant and has a detrimental effect on the organs of the reproductive system, the period of implantation and the development of embryos. The experiment presented in this article established the effect of cadmium salts (chloride and citrate) on the general progress of embryogenesis. For this purpose, 60 rats were randomly divided into three groups: control, experimental group with cadmium chloride exposure and experimental group with cadmium citrate exposure. Cadmium chloride solvent, cadmium citrate solvent at a dose of 1.0 mg/kg and distilled intragastric water were injected from the first to the thirteenth (first subgroup) and from the first to the twentieth days of embryogenesis (second subgroup). When cadmium chloride was injected, total embryonic (by 4.24 and 3.67 times), pre-implantation (by 6.50 and 14.03 times) and post-implantation mortality (by 3.07 and 2.49 times) increased with a reduction of the number of surviving fetuses by 24.0% and 25.9% compared with the control group on the 13th and 20th days of embryogenesis respectively. At the same time, during exposure to cadmium citrate, indicators of total embryonic mortality increased by 4.02 and 3.52 times, pre-implantation mortality by 6.04 and 13.03 times, and post-implantation mortality by 3.09 and 2.26 times, and indicators of the number of live fetuses decreased by 18.3% and 22.2% in relation to the control group. When determining the accumulation of cadmium in embryos on the 20th day of gestation, polyelement analysis of biological materials using the atomic emission method with electric arc atomization revealed a 15.83-fold increase in cadmium chloride and 9.00 times in cadmium citrate relative to the control group. Embryolethality rates increased in animals of both experimental groups while the number of live fetuses per female decreased, which indicated an obvious embryotoxic effect of cadmium compounds. It is would be useful to conduct histological studies, which will help detect changes at the tissue level and possibly explain the level of embryonic mortality.

Ameliorative effect of Azima tetracantha extract on Cadmium induced Hepato-Renal oxidative stress: An in vivo approach

Cadmium (Cd), an environmental pollutant affects humans through contaminated foodstuffs and industrial processes. Cd accumulates in various organs upon exposure and the primary targets are kidney and liver. Its toxicity induces free radicals, creating oxidative stress, defects in antioxidant mechanism, damage to membrane proteins, DNA damage, necrosis, and apoptosis. In this study hepatoprotective and nephroprotective activity of Azima tetracantha towards Cd-induced toxicity was investigated by in vivo approach. Ultra Violet (UV) spectral and Fourier Transform Infra-Red (FTIR) analysis of methanol extract of the Azima tetracantha leaves revealed phenolic compounds. Cadmium Chloride (CdCl2) exposure in Wister Albino rats showed a marked increase in lipid profile, enzymatic antioxidants, and non-enzymatic antioxidants. Co-administration of a methanol extract of Azima tetracantha leaves (500 mg/kg/day) with CdCl2 resulted in the reversal of toxicity effects in the kidney and hepatic cells by maintaining the normal histological architecture. Further, reduced lipid peroxidation and increased antioxidant defense system activity were observed. Hence, the current study suggests that the nephroprotective and hepatoprotective efficacy of Azima tetracantha in Cd-induced toxicity might result from its antioxidant and metal chelating characteristics that might benefit in reaching the best remedy in Cd-induced damage.

The imprinted gene Zac1 regulates steatosis in developmental cadmium-induced nonalcoholic fatty liver disease.

Cadmium (Cd) exposure in adulthood is associated with nonalcoholic fatty liver disease (NAFLD), characterized by steatosis, inflammation, and fibrosis. The prevalence of NAFLD in children is increasing, suggesting a role for the developmental environment in programming susceptibility. However, the role of developmental Cd exposure in programming NAFLD and the underlying mechanisms remain unclear. We have proposed that imprinted genes are strong candidates for connecting the early life environment and later life disease. In support of this, we previously identified roles for the Imprinted Gene Network (IGN) and its regulator Zac1 in programming NAFLD in response to maternal metabolic dysfunction. Here, we test the hypothesis that developmental Cd exposure is sufficient to program NAFLD, and further, that this process is mediated by Zac1 and the IGN. Using mice, we show that developmental cadmium chloride (CdCl2) exposure leads to histological, biochemical, and molecular signatures of steatosis and fibrosis in juveniles. Transcriptomic analyses comparing livers of CdCl2-exposed and control mice show upregulation of Zac1 and the IGN coincident with disease presentation. Increased hepatic Zac1 expression is independent of promoter methylation and imprinting statuses. Finally, we show that over-expression of Zac1 in cultured hepatocytes is sufficient to induce lipid accumulation in a Pparγ-dependent manner and demonstrate direct binding of Zac1 to the Pparγ promoter. Our findings demonstrate that developmental Cd exposure is sufficient to program NAFLD in later life, and with our previous work, establish Zac1 and the IGN as key regulators of prosteatotic and profibrotic pathways, two of the major pathological hallmarks of NAFLD.

Вплив солей кадмію на морфометричні показники яєчників щурів в експерименті

The purpose of the study was to experimentally study and compare the morphometric parameters of the ovaries of rats against the background of exposure to chloride and cadmium citrate during 13 or 20 days of gestation. Materials and methods. The study was carried out on 60 adult white female Wistar rats weighing 170–200 g, divided into 3 groups, depending on the intragastric administration of solutions of the studied metals – rats receiving cadmium chloride at a dose of 1.0 mg/kg – Group 1 (n females = 20); cadmium citrate at a dose of 1.0 mg/kg – Group 2 (n females = 20), Group 3 – control (n females = 20) – a proportional volume of sterile saline in the same way. In each experimental group, the females were divided into 2 subgroups of 10 animals each, depending on the duration of the administration of the test substances (13 or 20 days), the possible effect of which on the morphometric parameters of the ovaries was determined by the change in the average absolute and relative weight, volume, specific gravity and number of corpus luteum in the ovaries. Results and discussion. It was established that under the action of cadmium salts (chloride and citrate) the weight indices of rats of the experimental groups decreased by 4.2%-8.9% relative to the control group. In the cadmium chloride exposure group, the indicators of absolute mass, relative mass and volume of the ovaries increased as on the 13th day by 7.1%; 14.4%; 14.6%, and on the 20th day by 9.3%; 15.0%; 5.2% respectively. The same trend was observed in the group of action of cadmium citrate: the listed indicators increased by 3.2% on the 13th day of gestation by 12.0%; 5.63%, and on the 20th day by 3.7%; 5.4%; 13.9%, respectively, which is presumably due to edema and hypertrophy. When analyzing the specific gravity of the ovaries – an integral indicator that reflects the mass, linear dimensions and volume of organs, it was found that on the 13th day of gestation, both under the action of cadmium chloride and cadmium citrate, this indicator decreased by 3.12% (D No.1) and 2.08% (D No.2). On the 20th day of pregnancy in the experimental group No. 1, this indicator decreased by 1.03%, while in the experimental group No. 2 it increased by 2.1%, which indicates the compaction of the organ. The analysis of the obtained results showed that on the 13th day of gestation, the lowest average value of the number of corpus luteum per 1 female was observed in the group exposed to cadmium chloride and amounted to 10.00±0.27, the highest one was in the control group on the 20th day and amounted to 11.00±0.71. Conclusion. The results obtained demonstrate changes in the morphometric parameters of the ovaries of pregnant female rats with intragastric administration of cadmium chloride and cadmium citrate to Wistar rats at a dose of 1.0 mg/kg (in terms of metal), and are expressed in an increase in absolute and relative weight and indicate the toxic effect of the studied substances on the gonads of experimental animals

Evodiamine attenuates cadmium-induced nephrotoxicity through activation of Nrf2/HO-1 pathway

Purpose: To investigate the protective role of evodiamine, a naturally occurring anti-inflammatory, antioxidant, and anti-apoptotic compound, against cadmium-induced cytotoxicity in proximal tubular cells (human kidney 2; HK-2).&#x0D; Methods: HK-2 cells were treated with different concentrations of evodiamine (5, 20, 50 μM) for 2 h and then incubated with 40 μM cadmium chloride for another 24 h. Cell viability and apoptosis were evaluated using thiazolyl blue tetrazolium bromide (MTT) and flow cytometry, respectively. Oxidative stress was assayed by measuring the levels of malonaldehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GSH-PX).&#x0D; Results: Cadmium chloride treatment in HK-2 cells significantly reduced cell viability (p &lt; 0.01) and increased apoptosis compared to the control. Evodiamine pretreatment attenuated the cadmium chloride-provoked decrease in cell viability and increase in apoptosis. Evodiamine also decreased expression of cleaved caspase-3 and cleaved caspase-9 in HK-2 cells. Cadmium chloride exposure provoked kidney injury, as evidenced by increased MDA levels and decreased SOD, GSH, and GSH-PX levels. Pretreatment with evodiamine ameliorated kidney injury, as shown by decreased MDA expression and increased SOD, GSH, and GSH-PX expression. Evodiamine exposure significantly enhanced protein expression of nuclear factor erythropoietin-2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1).&#x0D; Conclusion: Evodiamine exerts an anti-apoptotic and anti-oxidative effect against cadmium chloride-induced nephrotoxicity via Nrf2/HO-1 pathway activation. These findings represent a potential therapeutic strategy for cadmium-provoked nephrotoxicity.

Toxicopathological effects of acute cadmium chloride exposure of African Catfish, Clarias gariepinus

Toxicopathological effects of acute cadmium chloride exposure of African Catfish, Clarias gariepinus

Toxic Effect of Cadmium Chloride Exposure on Teeth Development in Sprague Dawley Rats During Pregnancy

Toxic Effect of Cadmium Chloride Exposure on Teeth Development in Sprague Dawley Rats During Pregnancy

Heme oxygenase 1 plays a crucial role in swamp eel response to oxidative stress induced by cadmium exposure or Aeromonas hydrophila infection.

Oxidative stress contributes a lot to initiation and progression of pathological conditions. Heme oxygenase 1 (HO1), a cytoprotective enzyme, is usually upregulated to alleviate oxidative stress in vivo. The function of teleost HO1 in the response to oxidative stress induced by heavy metal exposure and in pathogenic bacterial infection remains uncertain. In the present study, both complementary DNA and genomic sequence of a HO1-like gene cloned from the liver of swamp eel (Monopterus albus) are reported. Sequence analysis showed that the putative amino acid sequence contained a conserved heme oxygenase signature and displayed higher similarity to HO1 genes of other teleosts. Expression profile of swamp eel HO1 was investigated in healthy tissues and in tissues following stimulation with pathogenic bacteria (Aeromonas hydrophila) or cadmium chloride (CdCl2) exposure. Results demonstrated that HO1 messenger RNA (mRNA) was highly expressed in the liver and relatively less in other tissues. Bacterial infection with A. hydrophila significantly changed HO1 mRNA expression in the liver, spleen, and kidney, and the mRNA expression of HO1 and Nrf2 in the liver was elevated after the fish were exposed to CdCl2. Subsequently, the swamp eel HO1 was subcloned into a pET28a expression vector and transformed into Escherichia coli BL21 (DE3). Recombinant HO1 (rHO1) was successfully induced by 0.1mmol/l IPTG and purified by Ni-NTA His Bind Resin purification system. To determine whether the rHO1 could confer stress tolerance in vitro, the viability of control and HO1-expressing E. coli under CdCl2 stress was compared by spot assay. The rHO1 protein significantly increased survival rates of the bacterial hosts. To evaluate whether intraperitoneal injection with rHO1 protected the liver of swamp eel against A. hydrophila-induced oxidative stress, mRNA expression of HO1, Nrf2, hepcidin, and IL-1β as well as the oxidative stress-related parameters (ROS and total antioxidant capacity (T-AOC)) in the liver were examined. The results showed that exogenous rHO1 could significantly upgrade the mRNA expression of HO1 and hepcidin, coupled with increased ROS and T-AOC levels. However, Nrf2 and IL-1β expression levels were significantly downregulated and upregulated, respectively. These results suggested that HO1 should not only play a protective role in oxidative stress response and its adverse effects deserved further investigation.

Parental exposure to cadmium chloride causes developmental toxicity and thyroid endocrine disruption in zebrafish offspring

Cadmium is a common heavy metal pollutant. Previous studies have found that long-term cadmium exposure can cause damage to multiple organs/systems in humans and experimental animals; however, there are few studies that elucidate its effects on offspring development, discuss whether it can be transmitted to offspring from the parent, and debate whether it affects the functional development of the thyroid hormone system in offsprings. In this study, sexually mature zebrafish were exposed to different concentrations of cadmium chloride (0.01 μmol/L, 0.1 μmol/L, and 1 μmol/L) to study reproductive toxicity. It was found that parental zebrafish exposed to 1 μmol/L of cadmium chloride produced offsprings with different degrees of malformation. At 5 days post-fertilization (dpf), the levels of 3,5,3′-triiododenosine (T3) and thyroxine (T4) in the zebrafish were decreased. At 10 dpf, the T4 and T3 levels in the zebrafish of the offspring were significantly reduced. At the same time, the expression of thyroid receptor (trα and trβ) genes in five dpf larvae was significantly up-regulated in the 1 μmol/L treatment group relative to the control group. The mRNAs of thyroid hormone synthesis and metabolism-related genes (tshβ, dio1, dio2, ugt1ab, and ttr) were significantly up-regulated in the 0.1 μmol/L and 1 μmol/L treatment groups. This study demonstrates that parental cadmium chloride exposure produces reproductive toxicity in zebrafish and that the effects can be transferred from the parent to the offspring, resulting in developmental toxicity in the thyroid endocrine system.

Second generation effects of larval metal pollutant exposure on reproduction, longevity and insecticide tolerance in the major malaria vector Anopheles arabiensis (Diptera: Culicidae)

BackgroundMembers of the Anopheles gambiae complex breed in clean, sunlit temporary bodies of water. Anthropogenic pollution is, however, altering the breeding sites of the vectors with numerous biological effects. Although the effects of larval metal pollution have previously been examined, this study aims to assess the transgenerational effects of larval metal pollution on the major malaria vector An. arabiensis.MethodsTwo laboratory strains of An. arabiensis, SENN (insecticide-susceptible) and SENN-DDT (insecticide-resistant), were used in this study. After being bred in water polluted with either cadmium chloride, copper nitrate or lead nitrate, several life history characteristics that can have epidemiological implications (fertility, apoptotic damage to reproductive structures, adult longevity and insecticide tolerance) were examined in the adults and compared to those of adults bred in clean water.ResultsAll metal treatments reduced fecundity in SENN, but only lead treatment reduced fertility in SENN-DDT. Cadmium chloride exposure resulted in apoptosis and deformation of the testes in both strains. After breeding generation F0 in polluted water, F1 larvae bred in clean water showed an increase in longevity in SENN-DDT adult females. In contrast, after breeding the F0 generation in polluted water, longevity was reduced after cadmium and copper exposure in the F1 generation. Larval metal exposure resulted in an increase in insecticide tolerance in adults of the SENN strain, with SENN-DDT adults gaining the greatest fold increase in insecticide tolerance.ConclusionsThis study demonstrates that a single exposure to metal pollution can have transgenerational effects that are not negated by subsequent breeding in clean water.