Plasma Cadmium Research Articles

Effects of multiple metals exposure on abnormal liver function: The mediating role of low-density lipoprotein cholesterol

Equilibration of metal metabolism is critical for normal liver function. Most epidemiological studies have only concentrated on the influence of limited metals. However, the single and synergistic impact of multiple-metal exposures on abnormal liver function (ALF) are still unknown. A cross-sectional study involving 1493 Chinese adults residing in Shenzhen was conducted. Plasma concentrations of 13 metals, including essential metals (calcium, copper, cobalt, iron, magnesium, manganese, molybdenum, zinc, and selenium) and toxic metals (aluminum, cadmium, arsenic, and thallium) were detected by the inductively coupled plasma spectrometry (ICP-MS). ALF was ascertained as any observed abnormality from albumin, alanine transaminase, aspartate transaminase, γ-glutamyl transpeptidase, and direct bilirubin. Diverse statistical methods were used to evaluate the single and mixture effect of metals, as well as the dose-response relationships with ALF risk, respectively. Mediation analysis was conducted to evaluate the role of blood lipids in the relation of metal exposure with ALF. The average age of subjects was 59.7 years, and 56.7 % were females. Logistic regression and the least absolute shrinkage and selection operator (LASSO) penalized regression model consistently suggested that increased levels of arsenic, aluminum, manganese, and cadmium were related to elevated risk of ALF; while magnesium and zinc showed protective effects on ALF (all p-trend < 0.05). The grouped weighted quantile sum (GWQS) regression revealed that the WQS index of essential metals and toxic metals showed significantly negative or positive relationship with ALF, respectively. Aluminum, arsenic, cadmium, and manganese showed linear whilst magnesium and zinc showed non-linear dose-response relationships with ALF risk. Mediation analysis showed that LDL-c mediated 4.41 % and 14.74 % of the relationship of plasma cadmium and manganese with ALF, respectively. In summary, plasma aluminum, arsenic, manganese, cadmium, magnesium, and zinc related with ALF, and LDL-c might underlie the pathogenesis of ALF associated with cadmium and manganese exposure. This study may provide critical public health significances in liver injury prevention and scientific evidence for the establishment of environmental standard.

Short-term Effects of Cadmium Exposure on Blood Pressure and Vascular Function in Wistar Rats.

Chronic cadmium exposure is known to be associated with vascular changes and increased blood pressure, but its short-term effects on the cardiovascular system remain poorly understood. This study aimed to investigate the pressoric and vascular effects of a 7-day exposure to CdCl2 in Wistar rats. The rats were divided in control group (Ct), which received tap water, and the Cd group, which received a 100mg/L CdCl2 solution via drinking water for 7days. We analyzed body weight, plasma Cadmium concentration, systolic blood pressure (SBP), and vascular responses. Despite relatively low plasma Cadmium concentration, the Cd group exhibited elevated SBP and increased contractile response to phenylephrine. Endothelium removal and NOS inhibition increased contractions in both groups. In the Cd group's aorta, we observed enhanced levels of phospho-eNOS (Ser1177) and basal NO release. Cd group showed reduced Catalase expression and increased basal release of H2O2, with catalase reducing the contractile response. In arteries pre-contracted with phenylephrine, Cd group showed impaired endothelium-dependent (Acetylcholine) and independent (sodium nitroprussiate-SNP) relaxation responses. However, responses to SNP were similar after pre-contraction with KCl in both groups. These data suggest early effects of Cadmium on blood pressure and aortic function, indicating impaired H2O2-scavenging by catalase. Increased H2O2 due to Cadmium exposure might explain heightened responses to phenylephrine and weakened relaxation responses mediated by the NO-K+-channels pathway. Our findings shed light on Cadmium's short-term impact on the cardiovascular system, providing insights into potential mechanisms underlying its effects on blood pressure regulation and vascular function.

Plasma selenium and zinc alter associations between nephrotoxic metals and chronic kidney disease: Results from NHANES database 2011-2018.

Chronic kidney disease (CKD) is a condition defined as a persistent change in kidney structure or function, or both, that compromises human health. Environmental exposure to heavy metals (e.g. cadmium, lead, arsenic and mercury) is common, and high exposure levels are known to cause nephrotoxicity. Micronutrients such as selenium and zinc are positively associated with better kidney function and renal outcomes. This study determined the associations between CKD and heavy metal exposures measured in blood or urine within a community-dwelling population, and assessed whether and how selenium and zinc modified the associations. Data were extracted from 4 cycles of the US National Health and Nutrition Examination Survey (NHANES) database (2011-2012, 2013-2014, 2015-2016 and 2017-2018). Univariate analysis showed that higher quartiles of plasma lead and cadmium concentration were more likely associated with CKD than the lowest quartile, and along with folate, were linked to greater odds of CKD. Conversely, as plasma selenium and serum zinc increased, the odds of CKD decreased. Multivariate analysis had similar results after adjusting for relevant confounders. Higher plasma cadmium quartiles were associated with higher odds of CKD. Associations between higher quartiles of plasma selenium and serum zinc were significantly associated with lower odds of CKD. Elevated blood levels of heavy metals increase CKD, whereas elevated concentrations of plasma selenium and serum zinc decrease CKD. A high serum zinc concentration appears to interact with low-toxicity heavy metals to reduce CKD risk. This study suggests that increased selenium and zinc in the body along with avoidance of heavy metal exposures could protect against CKD.

#2981 IRON DEFICIENCY AND CADMIUM LEVELS IN KIDNEY TRANSPLANT RECIPIENTS

Abstract Background and Aims A higher plasma level of cadmium, a nephrotoxic divalent heavy metal, has been associated with an increased risk of graft failure in kidney transplant recipients (KTRs). The drivers of cadmium toxicity in KTRs are incompletely understood. We hypothesize that iron deficiency (ID) increases cadmium absorption and accumulation by upregulation of divalent metal transporters. Here, we first investigated whether ID is associated with higher plasma cadmium levels. As increased cadmium levels have previously been associated with cancer, cardiovascular disease, and diabetes in other populations, we also examined whether plasma cadmium levels are associated with all-cause mortality in KTRs. Method We used data from stable KTRs ≥1 year after transplantation who participated in the TransplantLines Food and Nutrition Cohort study. Plasma cadmium and iron status parameters, i.e., ferritin, iron, and transferrin saturation (TSAT), were measured at baseline. ID was defined as TSAT&amp;lt;20% and ferritin &amp;lt;300 µg/L. Linear regression analyses were applied to study the association between iron status parameters and cadmium levels. Multivariable Cox regression analyses were used to investigate the association of plasma cadmium levels with all-cause mortality, adjusted for age, sex, BMI, smoking status, history of cardiovascular disease, glucose, HbA1c, systolic blood pressure, eGFR, cholesterol, and ID at baseline. In sensitivity analyses, we repeated these analyses using an alternative definition of ID, TSAT&amp;lt;20% and ferritin&amp;lt;100 µg/L (IDalt). Results We included 670 KTRs (age 53±13 years, 58% males, median 5.4 (IQR, 1.9-11.7) years after transplantation). KTRs with ID (30% of all KTRs, median plasma cadmium level 63 (IQR, 48-76) ng/L) had higher cadmium levels than KTRs without ID (median 56 (IQR, 42-75) ng/L, P = 0.01, Figure 1). ID was not associated with plasma cadmium after adjustment for age, sex, and smoking status. However, within the ID group, TSAT (β = -0.016, P = 0.01) and serum iron (β = -0.023, P = 0.01) were inversely associated with log-transformed cadmium levels, independently of age, sex, and smoking status. Sensitivity analysis yielded similar results: KTRs with IDalt (23% of all KTRs) had higher cadmium levels than KTRs without IDalt (median 61 (IQR, 49-76) ng/L vs median 57 (IQR, 42-75) ng/L, P = 0.03). Furthermore, in Cox regression analysis, KTRs in the highest tertile of plasma cadmium levels (70 ng/L to 330 ng/L) had an increased risk of mortality (hazard ratio 2.80, 95%CI 1.47-5.36, P = 0.01) compared to KTRs in the lowest cadmium tertile (19 ng/L to 48 ng/L) during a median follow-up of 4.9 (IQR, 3.5-5.5) years. No significant interaction by iron status was observed for the association between plasma cadmium and mortality. Conclusion KTRs with ID had higher cadmium levels than KTRs without ID, and higher plasma cadmium levels were independently associated with a higher mortality risk. The association of cadmium with mortality was not different between individuals with and without ID at baseline. Further investigations should determine whether ID correction prevents cadmium accumulation in KTRs.

Evaluation of Heavy Metal (Lead, Mercury, Cadmium, and Manganese) Levels in Blood, Plasma, and Urine of Adolescents With Aggressive Behavior.

Background Heavy metals can cause health problems by affecting the biological structure even at very low concentrations. Asymptomatic heavy metal poisoning causes non-specific symptoms such as behavioral disorders, difficulty in learning, and aggressive behaviors. There is also a great concern about the incidence of aggressive behavior among adolescents. A few research studies have concluded that a complex interaction or combination of factors leads to an increased risk of aggressive behavior in adolescents. This study aims to determine the correlation between the heavy metal levels in blood, plasma, and urine and the aggression level in adolescents. Materials and methods Two hundred twenty-eight adolescents between the ages of 13 and 19 were enrolled in the study. Blood, plasma, and urine heavy metal levels of the participants were measured by an inductively coupled plasma mass spectrometer (ICP-MS) device (Model 7700x; Agilent, Santa Clara, CA, USA). Buss and Perry's aggression questionnaire was used to investigate the correlation between heavy metals and aggressive behaviors in adolescents. Results Lead blood (r=0.34, p<.01), lead plasma (r=0.22, p<0.01), lead urine (r=0.31, p<.01), mercury blood (r=0.35, p<0.01), mercury urine (r=0.21, p<0.01), manganese blood (r=0.34, p<0.01), manganese plasma (r=0.33, p<0.01) and manganese urine (r=0.39, p<0.01) were positively correlated with tendency to aggression whereas no significant relationship was found between cadmium in blood, plasma, urine and mercury in plasma with aggression. Conclusion The study showed valuable data to associate a significant relationship between adolescents' aggression levels and heavy metals. There is an undeniable relationship between the health of adolescents and environmental pollution caused by heavy metals. Therefore, taking the necessary measures to prevent environmental heavy metal pollution is crucial for adolescent health.

Sex-dependent vascular effects of cadmium sub-chronic exposure on rats.

Cadmium exposure is related to several cardiovascular diseases, such as hypertension, atherosclerosis and endothelial dysfunction. However, the toxic effect of cadmium can be dependent on the sex when examined sex in experimental models. The aim of this study was to analyze the effects of cadmium exposure on the cardiovascular system of male and female rodents. The experiments were carried out on both-sexes Wistar at 4months of age, where from 3months onwards, cadmium (CdCl2 100mg/l in placed the drinking water for 30days) or vehicle delivered (distilled water) was ingested. Before and after 30days of exposure to cadmium, systolic blood pressure was regularly measured. After exposure, blood was collected to measure dosage of cadmium, in male and female, and estrogen in females. Vascular reactivity to phenylephrine (Phe), acetylcholine (ACh), and sodium nitroprusside (SNP) was studied at respective isolated aortic segments. After the period to Cd-exposure, systolic blood pressure was increased only in the male rats. Males also had higher levels of plasma cadmium than those of female rats, and exposure to the metal did not affect the amount of estrogen produced in the female rats. Increased myeloperoxidase (MPO) activity was also observed in both the males and females that had been exposed to the metal. Moreover, exposure to the cadmium reduced the ACh relaxation and increased vascular reactivity to Phe, resulting in an imbalance between nitric oxide superoxide anion in the isolated aorta of male rats. In female rats, sub-chronic cadmium exposure did not modify the vascular reactivity to Phe and neither to the ACh. The present study revealed that the Cd exposure for 30days induced sex-dependent cardiovascular abnormalities.

Evaluation of plasma cadmium levels in pregnancy and outcome implications, Kinshasa, DR Congo

Evaluation of plasma cadmium levels in pregnancy and outcome implications, Kinshasa, DR Congo

Association between plasma cadmium and renal stone prevalence in adults in rural areas of Guangxi, China: a case–control study

BackgroundKidney stones have become a worldwide public health problem. The purpose of this research is to study the relationship between plasma cadmium level and the prevalence of kidney stones in an adult population.MethodsThe data of this study were based on a current survey conducted from December 2018 to November 2019 in Gongcheng Yao Autonomous County, Guangxi, China. A total of 940 study subjects of the same sex and age (within 2 years of each other) according to 1:1 matching were selected for a case–control study. The diagnosis of kidney stones was based on the presence of strong light spots, patches, clusters, or bands within the renal sinus region, followed by an echo-free bundle of acoustic images. Plasma metal elements were determined by the metal plasma method. The relationship between plasma cadmium concentration and the prevalence of kidney stones was assessed using logistic regression and restricted cubic spline regression.ResultsThe crude ratio for kidney stones in the highest quartile of plasma cadmium was 1.164 (95% CI, 1.121 to 2.324) compared with the lowest quartile. A positive correlation was found between the two (P for trend = 0.039). After adjusting for potential confounders, the ratio of plasma cadmium to kidney stones in the highest quartile was 1.606 (95% CI, 1.100 to 2.344) compared with the lowest quartile, and the findings remained unchanged.ConclusionThe odds of kidney stones in adults increased with increasing plasma cadmium exposure, and high plasma cadmium may be a risk factor for kidney stones.

Plasma Concentration of Essential and Toxic Trace Elements After Brazil Nut Intake: Results from a Randomized Controlled Trial.

Brazil nut (BN) is a good source of essential nutrients, but little is known about the content of other components, such as toxic elements. Moreover, the high consumption of BN could probably contribute to increased levels of toxic and essential elements in the blood. Thus, this study aimed to evaluate the concentration of essential and toxic trace elements in BN and their concentration in plasma of obese women after regular intake of BN. A randomized controlled clinical trial was carried out with 55 subjects that were randomly assigned to either the Brazil nut group (BN) (n = 29) or the control group (CO) (n = 26) and followed up for 2 months. The BN group consumed one unit of Brazil nut per day, and the CO group did not receive any intervention. The concentration of essential elements (zinc, copper, manganese, and cobalt) and toxic (barium, lead, and cadmium) in BN samples and plasma of obese women (before and after the intervention) were determined by inductively coupled plasma mass spectrometry. Barium followed by copper, and manganese were the trace elements present in higher amounts in Brazil nuts. After the BN intervention period was observed an increase in plasma cadmium (p = 0.002) and a reduction of plasma manganese (p < 0.001) levels. In conclusion, our findings suggest that the regular consumption of BN from the Brazilian Amazon rainforest contributes to the intake of essential trace elements and can be considered safe regarding the content of heavy metals.

Epidermal Growth Factor Receptor (EGFR) Gene Polymorphism May be a Modifier for Cadmium Kidney Toxicity.

The results of many studies indicate that cadmium (Cd) exposure is harmful to humans, with the proximal tubule of the kidney being the main target of Cd accumulation and toxicity. Studies have also shown that Cd has the effect of activating the pathway of epidermal growth factor receptor (EGFR) signaling and cell growth. The EGFR is a family of transmembrane receptors, which are widely expressed in the human kidney. The aim of this study was to investigate the kidney function estimated glomerular filtration rate (eGFR), and its relationship with plasma Cd level and EGFR gene polymorphism. Using data from Academia Sinica Taiwan biobank, 489 subjects aged 30–70 years were analyzed. The demographic characteristics was determined from questionnaires, and biological sampling of urine and blood was determined from physical examination. Kidney function was assessed by the eGFR with CKD-EPI formula. Plasma Cd (ug/L) was measured by inductively coupled plasma mass spectrometry. A total of 97 single-nucleotide polymorphisms (SNPs) were identified in the EGFR on the Taiwan biobank chip, however 4 SNPs did not pass the quality control. Multiple regression analyses were performed to achieve the study aim. The mean (±SD) plasma Cd level of the study subjects was 0.02 (±0.008) ug/L. After adjusting for confounding variables, rs13244925 AA, rs6948867 AA, rs35891645 TT and rs6593214 AA types had higher eGFR (4.89 mL/min/1.73 m2 (p = 0.035), 5.54 mL/min/1.73 m2 (p = 0.03), 4.96 mL/min/1.73 m2 (p = 0.048) and 5.16 mL/min/1.73 m2 (p = 0.048), respectively). Plasma cadmium and rs845555 had an interactive effect on eGFR. In conclusion, EGFR polymorphisms could be modifiers of Cd kidney toxicity, in which rs13244925 AA, rs6948867 AA, rs35891645 TT and rs6593214 AA may be protective, and Cd interacting with rs845555 may affect kidney function.

Exposure to multiple metals/metalloids and human semen quality: A cross-sectional study

BackgroundExposure to metals/metalloids, including essential and nonessential elements, has been associated to male reproductive health in animals. However, findings from human studies are inconsistent. ObjectivesTo investigate the impact of exposure to multiple metals/metalloids at environmental levels on the conventional human semen-quality parameters. Materials and methodsMen living in rural or industrial areas were recruited by personalized letters. No exclusion criteria were applied. Each man provided one semen sample and one blood sample. We analyzed the semen sample both to determine conventional sperm parameters (concentration, progressive motility and normal forms) and to quantify lead (Pb), cadmium (Cd), mercury (Hg), arsenic (As), nickel (Ni), vanadium (V) and selenium (Se) levels. The levels of these metals/metalloids were also quantified in venous blood and spermatozoa samples. Associations between the blood/seminal plasma metal/metalloid levels and semen quality parameters were assessed using confounder adjusted logistic regression models. Correlation and interactions between blood/seminal plasma and semen metal/metalloid levels were investigated using the Spearman’s correlation. ResultsWe found a positive association of seminal plasma cadmium level with lower Total count (OR = 4.48, 95%CI 0.25–80); whereas lead (OR = 4.51, 95%CI 0.86–23) and cadmium (OR = 3.45, 95%CI 0.77–16) seminal plasma levels had a positive association with progressive sperm motility. Overall, these associations remained suggestive after adjustment, though statistically unstable risks. Finally, we found weak interactions between beneficial effects of Se and detrimental ones only for Cd and Pb blood level on sperm concentration, total sperm count and progressive sperm motility. ConclusionsOur findings suggest that environmental exposure to Pb and Cd contributes to a decline in human semen quality, whereas Se can have beneficial effects. Measurements of metals/metalloids in the seminal fluid may be more predictable of semen quality than conventional blood measurements

Single-cell transcriptomics uncovers phenotypic alterations in the monocytes in a Chinese population with chronic cadmium exposure

BackgroundCadmium is the most prevalent form of heavy metal contaminant globally and its exposure rises serious health concern. Chronic exposure to cadmium causes immune disturbances. However, few studies have addressed how it affects circulating immune cells, one of the most essential elements for the host defense system, at both population and molecular level. Therefore, this is the first single-cell transcriptomic analysis of the response of the human circulating immune system to plasma cadmium level. MethodsWe conducted a cross-sectional study in Hunan province, which has the highest level of cadmium land contamination in China. A total of 3283 individuals were eligible for analyzing the association between plasma cadmium levels and the monocyte counts and its subgroups. Another 780 individuals were assigned for validation. Thirty propensity-matched individuals without chronic disease from the lowest- and highest-quartile groups according to serum cadmium levels were selected for single-cell RNA sequencing (scRNA-seq) and flow cytometry analyses. Moreover, the monocyte phenotypic alterations in the heavy metal-exposed population were validated with a cecal ligation and puncture sepsis mouse model. ResultsFrom August 2016 to July 2017, we conducted a cross-sectional study to identify phenotypic alterations in peripheral immune cells in cadmium polluted areas in China. Monocyte percentages were negatively associated with plasma cadmium levels in multivariable linear regression analysis. Peripheral blood mononuclear cell scRNA-seq revealed that the CD14+ monocyte subset was dramatically reduced in the highest-quartile cadmium-exposed group. Moreover, we assessed different hallmarks of immune cell dysfunction—such as host defense capability, apoptotic signaling, cellular diversity and malignant gene expression in monocytes. Importantly, cadmium induced phenotypic alterations in the immune system were validated in the cecal ligation and puncture sepsis mouse model, in which chronic exposure to cadmium not only increased the death rate but also decreased monocyte numbers and the ability to clear bacterial infections. ConclusionThis transcriptomic analysis provides molecular information about how the most important hallmarks of immune cell dysfunction are affected by plasma cadmium level. The significant phenotypic alterations in monocytes serving as early indicators of increased susceptibility to infectious and malignant diseases.

Analyses of maternal plasma cadmium, lead, and vanadium levels in the diagnosis and severity of late-onset preeclampsia: a prospective and comparative study

Introduction Cadmium, lead, and vanadium, important pollutants produced from anthropogenic activities, have been suggested to be embryotoxic and fetotoxic in many studies. However, the causes of preeclampsia are little known and heavy metals merit further investigation. We tested whether late-onset preeclampsia (L-PrE) was associated with exposure to these metals. Methods This study was designed to determine maternal plasma cadmium, lead, and vanadium concentrations in women with L-PrE (n = 46) compared with those of normotensive women (n = 46). The concentrations of the metals were measured using inductively coupled plasma-mass spectrometry and compared. Results The groups were matched for maternal age, gestational age, and gravidity (p ≥ 0.05). Vanadium concentrations differed between the groups (p = 0.007). In contrast, there were no significant differences in the concentrations of cadmium and lead between the groups (p ≥ 0.05). There was no difference between the concentrations of the metals in patients with mild (n = 23) and severe (n = 23) preeclampsia in L-PrE (p ≥ 0.05). A significant discriminative role of vanadium for the presence of L-PrE, with a cutoff value of 1.84 µg/L, was found in ROC curve analysis. When the patients with and without small-for-gestational-age infants were compared (n = 12, and n = 80, respectively), it was determined that there were no differences between cadmium, lead, and vanadium concentrations (p ≥ 0.05). Conclusion Lower levels of vanadium might be associated with the development of L-PrE. Our findings require further investigation in other populations.

The effect of seminal plasma cadmium and lead levels on semen parameters in male subjects of infertile couples: a prospective cohort study

The aim of this prospective study was to investigate whether there is a relationship between seminal plasma cadmium (Cd) and lead (Pb) levels and semen parameters in male partners of infertile couples. Two hundred fifty one (251) men recruited with no history of occupational exposure to toxic metals. After semen analysis, seminal Cd and Pb levels were measured using atomic absorption spectrometry. Cadmium levels in men with hypospermia was significantly higher than men with normal semen volume (p = .049). In contrast, there was no statistically significant difference in median seminal Pb levels between men with hypospermia and men with normal semen volume (p = .13). There was no statistically significant association between seminal plasma Cd and Pb levels sperm concentration, motility, morphology and total progressively motile sperm count. These findings suggest that environmental Cd exposure may contribute to low semen volume in male partners of infertile couples. IMPACT STATEMENT What is already known on this subject? Toxic metals may adversely affect both male and female reproductive system. What the results of this study add? Seminal plasma cadmium levels in men with hypospermia were statistically significantly higher than men with normal semen volume. What the implications are of these findings for clinical practice and/or further research? Patients should be informed about possible adverse effects of toxic metals.

Plasma cadmium is associated with increased risk of long-term kidney graft failure

The kidney is one of the most sensitive organs to cadmium-induced toxicity, particularly in conditions of long-term oxidative stress. We hypothesized that, in kidney transplant recipients, nephrotoxic exposure to cadmium represents an overlooked hazard for optimal graft function. To test this, we performed a prospective cohort study and included 672 outpatient kidney transplant recipients with a functioning graft of beyond one year. The median plasma cadmium was 58 ng/L. During a median 4.9 years of follow-up, 78 kidney transplant recipients developed graft failure with a significantly different distribution across tertiles of plasma cadmium (13, 26, and 39 events, respectively). Plasma cadmium was associated with an increased risk of graft failure (hazard ratio 1.96, 95% confidence interval 1.56‒2.47 per log2 ng/L). Similarly, a dose-response relationship was observed over increasing tertiles of plasma cadmium, after adjustments for potential confounders (donor, recipient, transplant and lifestyle characteristics), robust in both competing risk and sensitivity analyses. These findings were also consistent for kidney function decline (graft failure or doubling of serum creatinine). Thus, plasma cadmium is independently associated with an increased risk of long-term kidney graft failure and decline in kidney function. Further studies are needed to investigate whether exposure to cadmium represents an otherwise overlooked modifiable risk factor for adverse long-term graft outcomes in different populations.

Cadmium exacerbates dextran sulfate sodium-induced chronic colitis and impairs intestinal barrier

The potential health risk of environmental pollutant, cadmium, has become a public concern due to its widespread existence and long biological half-life. High-dose cadmium can induce various adverse outcomes, however, the chronic biological influences of cadmium at an environmental dosage and its mechanism remain largely unclear. Here, we investigated the effect of long-term exposure of cadmium at the environmental-relevant concentration on intestinal function. A chronic colitis mouse model was established through multiple cycles of dextran sulfate sodium (DSS) challenge and recovery. 200 nM cadmium in drinking water intensified colonic inflammation induced by DSS (histological score, DSS vs. DSS + Cd: 7.4 ± 1.21 vs. 10.67 ± 0.67, P < 0.05), including fecal occult bleeding and fecal consistency loss. Multiple inflammatory cytokines were significantly up-regulated by cadmium both in colon and plasma (P < 0.05). In addition, intestinal integrity was compromised by cadmium. Goblet cells were markedly reduced (ctrl vs. Cd: 48.33 ± 3.07 vs. 37.5 ± 2.14, P < 0.05) and plasma D-lactate (ctrl vs. Cd: 1.88 ± 0.20 vs. 2.80 ± 0.15, P < 0.01) and diamine oxidase (ctrl vs. Cd: 5.00 ± 0.87 vs. 11.21 ± 2.17, P < 0.05) were increased in cadmium-treated mice, indicating an elevated intestinal permeability. In vitro results showed that long-term exposure of cadmium down-regulated the expression and membrane localization of adherent and tight junction proteins in a time-dependent manner. In conclusion, long-term exposure of environmental dose of cadmium aggravated DSS-induced chronic colitis and disrupted intestinal barrier and impaired the adherent and tight junction proteins. These findings provide a better understanding about the health risk of cadmium in the environment.

OKING : TOXIC EFFECTS 1N OSTEOARTHRITIS

The material for the present studyincluded 24 patients (18males &6femals) with osteoarthritis (OA) selectedfrom Rheumatology and rehabilitationout patients clinic MansouraUniversityHospital with age rangefrom(45-67 years). 16 patients wereheavysmokers consuming > 20 cigarette/day for long duration > 15yearswhile 8 patients were nonsmokers.8 normal (non smokers)healthyvolunteers with matched ageandsex served as control. All patientswere subjected to radiologicassessmentof (OA) using KellgrenLawrencegrading scal, and clinicalassessmentincluding body mass index(BMI) and WOMAC (WesternOntarioand McMaster universities)indexof osteoarthritis. Using Perkins Elmer atomic absorption spectrophotometry, both plasma cadmium (Cd)andlead (Pb) levels were found tobesignificantly increased among patients with OA exposed to intoxicationthrough heavy cigarette smokingforlong duration. A+ve correlationwasfound between plasma Cd & Pblevelsand severity of OA. Also plasmaCd & Pb levels were found to besignificantlyincreased among, middleaged , slim (non obese) smokerswithOA compared with elderlyobesepatients. In light of previousfindingswe can conclude that exposureto toxic effect of smoking forlong duration may contribute to pathogenesisof OA even in absence ofsomeother risk factors such as olderageand obesity

SUN-309 PLASMA CADMIUM AND RISK OF LATE GRAFT FAILURE AND KIDNEY FUNCTION DECLINE IN KIDNEY TRANSPLANT RECIPIENTS

The kidney is the most sensitive organ to cadmium-induced toxicity, particularly in conditions of long-term ongoing oxidative stress. We hypothesized that, in kidney transplant recipients (KTR), the nephrotoxic exposure to cadmium represents an overlooked hazard for preserved graft functioning. We performed a longitudinal cohort study of 672 adult KTR with a functioning graft ≥1 year, recruited at a university setting (2008-2011). A Kaplan-Meier curve, log-rank test, and multivariable-adjusted Cox proportional-hazards regression analyses were performed to assess the prospective association of plasma cadmium with the primary endpoint death-censored graft failure (defined as restart of dialysis or re-transplantation) and the secondary endpoint kidney function decline (defined as doubling of serum creatinine or graft failure). Subgroup prospective analyses were performed according to significant effect-modifiers. Median plasma cadmium was 58 (IQR, 43‒75) ng/L. During 4.9 (IQR, 3.4‒5.5) years of follow-up, 78 KTR developed graft failure (13, 26, and 39 events across tertiles of cadmium; P<0.001). Plasma cadmium associated with increased risk of graft failure (HR 1.96, 95% CI 1.56‒2.47 per 2log ng/L; P<0.001), particularly among patients with abnormal liver enzyme levels (HR 2.62, 95% CI 1.73‒3.95 per 2log ng/L; P<0.001). A dose-response relationship was observed, with a HR of 2.67 (95% CI 1.36‒5.26 per 2log ng/L; P<0.001) and 4.31 (95% CI 2.25‒8.22 per 2log ng/L; P<0.001) for patients in tertile 2 and 3 of plasma cadmium distribution, respectively. Our findings were independent of adjustment for donor, recipient, and transplant characteristics, robust in sensitivity analyses without outliers, and consistent over the secondary end-point kidney function decline. A seemingly significant association of cadmium with all-cause mortality was lost in graft failure-censored analyses.Table 1Association of plasma cadmium with risk of death-censored graft failure (nevents=78) and kidney function decline (nevents=95)ModelsCadmium per 2log (ng/L)HR (95% CI)P valueDeath-Censored Graft FailureCrude1.89 (1.47‒2.43)<0.001Model 11.96 (1.56‒2.47)<0.001Model 21.96 (1.40‒2.75)<0.001Model 31.96 (1.40‒2.76)<0.001Model 42.01 (1.45‒2.79)<0.001Kidney Function DeclineCrude1.66 (1.29‒2.15)<0.001Model 11.78 (1.41‒2.26)<0.001Model 21.77 (1.28‒2.44)0.001Model 31.75 (1.27‒2.42)0.001Model 41.75 (1.27‒2.42)<0.001 Open table in a new tab Multivariable model 1 was adjusted for age and sex. Subsequently, additive adjustment was performed for eGFR, proteinuria, primary kidney disease, transplant vintage, acute rejection, cold ischemia time, human leukocyte antigens mismatches, and deceased donor status (model 2); body mass index, systolic blood pressure, blood glucose, and presence of diabetes (model 3); and, smoking and alcohol use (model 4). View Large Image Figure ViewerDownload Hi-res image Download (PPT) In KTR, plasma cadmium is independently associated with increased risk of kidney function decline and late graft failure. Cadmium-targeted interventions may represent novel risk-management strategies to decrease the burden of late kidney graft failure.

Variation in contamination status of cadmium in forages and blood plasma of livestock in different districts of Punjab, Pakistan

Variation in contamination status of cadmium in forages and blood plasma of livestock in different districts of Punjab, Pakistan

Cadmium exposure enhances organic cation transporter 2 trafficking to the kidney membrane and exacerbates cisplatin nephrotoxicity

Renal accumulation and exposure of cadmium originating from pollution in agricultural land and the prevalence of cigarette smoking remains an unneglectable human health concern. Whereas cadmium exposure has been correlated with increased incidence of a variety of kidney diseases, little is known pertaining to its effect on renal drug disposition and response in patients. Here, we report that cadmium exposure significantly increased the activity of organic cation transporter 2 (OCT2), a critical renal drug transporter recommended in United States Federal Drug Administration guidance for assessment during drug development. Cadmium enhanced OCT2 trafficking to the cell membrane both invitro and invivo. Mechanistically cadmium-mediated OCT2 translocation was found to involve protein-protein interaction between serine/threonine-protein kinase AKT2, calcium/calmodulin and the AKT substrate AS160 in invitro cellular studies. The formed protein complex could selectively facilitate phosphorylation of AKT2 at T309, which induced translocation of OCT2 to the plasma membrane. Moreover, cadmium exposure markedly exacerbated nephrotoxicity induced by cisplatin, an OCT2 substrate, by increasing its accumulation in the mouse kidney. Consistently, there was a significant correlation between plasma cadmium level and alteration of renal function in cervical cancer patients who underwent chemotherapy with cisplatin. Thus, our studies suggest that membrane transporter distribution induced by cadmium exposure is a previously unrecognized factor for the broad variation in renal drug disposition and response.