Dietary Cd Research Articles

Alterations of mitochondrial antioxidant indexes and apoptosis in duck livers caused by Molybdenum or/and cadmium

Cadmium (Cd) and high Molybdenum (Mo) can lead to adverse reactions on animals, but the co-induced toxicity of Mo and Cd to liver in ducks was not well understood. To investigate the co-induced toxic effects of Mo combined with Cd on mitochondrial oxidative stress and apoptosis in duck livers. 240 healthy 11-day-old ducks were randomly divided into 6 groups (control, LMo group, HMo group, Cd group, LMoCd group and HMoCd group). After being treated for 30, 60, 90 and 120 days, liver mitochondrial antioxidant indexes, ceruloplasmin (CP), metallothionein (MT), Bak-1 and Caspase-3 genes mRNA expression levels, and ultrastructural changes were evaluated. The results showed that total antioxidative capacity (T-AOC), catalase (CAT), superoxide dismutase (SOD) and xanthine oxidase (XOD) activities in experimental groups were decreased, whereas malondialdehyde (MDA) content and nitric oxide synthase (NOS) activity were increased compared with control group, and these changes of co-treated groups were more obvious in the later period of the experiment. The mRNA expression levels of CP, Bak-1 and Caspase-3 were up-regulated in experimental groups compared with control group and showed significant difference between co-treated groups and single treated groups. The mRNA expression level of MT in Cd group was higher than that in co-treated groups. Additionally, ultrastructural changes showed karyopyknosis, mitochondrial swelling, vacuolation and disruption of mitochondrial cristae in co-treated groups. Taken together, it was suggested that dietary Mo and Cd might lead to mitochondrial oxidative stress and apoptosis in duck livers, and it showed a possible synergistic relationship between the two elements.

Knockout of OsNramp5 using the CRISPR/Cas9 system produces low Cd-accumulating indica rice without compromising yield

Rice grain with excessive cadmium (Cd) is a major source of dietary Cd intake and a serious threat to health for people who consume rice as a staple food. The development of elite rice cultivars with consistently low Cd content is challenging for conventional breeding approaches, and new strategies urgently need to be developed. Here, we report the development of new indica rice lines with low Cd accumulation and no transgenes by knocking out the metal transporter gene OsNramp5 using CRISPR/Cas9 system. Hydroponic culture showed that Cd concentrations in shoots and roots of osnramp5 mutants were dramatically decreased, resulting in rescue of impaired growth in high Cd condition. Cd-contaminated paddy field trials demonstrated that Cd concentration in osnramp5 grains was consistently less than 0.05 mg/kg, in contrast to high Cd concentrations from 0.33 mg/kg to 2.90 mg/kg in grains of Huazhan (the wild-type indica rice). In particular, the plant yield was not significantly affected in osnramp5 mutants. Furthermore, we developed promising hybrid rice lines with extremely low Cd content in grains. Our work supplies a practical approach to developing Cd pollution-safe indica rice cultivars that minimizes Cd contamination risk in grains.

Mineral Dietary Supplement To Decrease Cadmium Relative Bioavailability in Rice Based on a Mouse Bioassay

To determine the effectiveness of mineral dietary supplements to modulate cadmium (Cd) exposure, an in vivo mouse bioassay was conducted to determine Cd relative bioavailability (Cd-RBA) in Cd-contaminated rice (0.80 mg Cd kg-1) with and without Zn, Fe, or Ca supplements as nitrate or chloride salts. Without mineral supplements, Cd-RBA was 43 ± 5.3% based on average Cd accumulation in the liver plus kidneys as the end point. Among Ca(NO3)2, Zn(NO3)2, and Fe(NO3)2 supplements, 150-5000 mg kg-1 Ca was the most effective in reducing rice Cd-RBA by 31-80% to 8.5-29%, while 30-200 mg kg-1 Zn supplements was ineffective, with Cd-RBA being 33-57%. Low Fe at <40 mg kg-1 had little impact on rice Cd-RBA (39-47%), while high Fe at 80-200 mg kg-1 decreased Cd-RBA by 37% to 26-27%. The ineffectiveness of Zn supplements in reducing Cd-RBA was probably due to coinciding 8.3- and 3.1-fold increases in Zn accumulation in mouse kidneys and liver with Zn supplements, while Ca and Fe supplements led to much-smaller increases in Ca and Fe accumulation in mouse tissues (1.3-1.6 fold). In addition, compared to Ca(NO3)2 supplements, Cd-RBA values determined with CaCl2 supplements were significantly higher (25-67% versus 8.5-29%), suggesting that chloride enhanced Cd-RBA. Results of this study have important implications for developing effective dietary strategies to reduce dietary Cd exposure and the associated health risks in humans.

Health risk assessment of Chinese consumers to Cadmium via dietary intake

This paper investigated the concentration of Cd in foods via surveys and a literature review. The concentration of Cd in different food groups was in the decreasing order of meat > aquatic products > cereal > vegetable > bean > egg > dairy > fruit. More precisely, on average the weekly Cd intake for men, women, 2–3-year-old children and 4–17-year-old children were 0.0039, 0.0041, 0.0069 and 0.0064mgkg−1 bw week−1, respectively. Among all food groups, cereal was the most significant contributor to the dietary intake of Cd, followed by vegetable, aquatic products and meat. For Chinese consumers, the results of risk assessment for all groups by the deterministic method and the probabilistic method showed the mean weekly Cd intake via dietary exposure was lower than the provisional tolerable weekly intake (PTWI) proposed by WHO. However, the 95th and 97.5th percentile THQ values all exceeded 1, and the probability of dietary Cd exposure greater than the weekly intake tolerance (THQ >1) were 15.9%, 17.1%, 42.3% and 28.4% for men, women, 2–3-year-old children and 4–17-year-old children, indicating a potential risk from Cd exposure via dietary intake, especially for children. It appeared that dietary Cd exposure should deserve our attention, and positive measures must be taken to reduce the concentration of Cd in food at once.

Effects of molybdenum and cadmium on the oxidative damage and kidney apoptosis in Duck

Molybdenum (Mo) is an essential element for human beings and animals; however, high dietary intake of Mo can lead to adverse reactions. Cadmium (Cd) is one of the major transitional metals which has toxic effects in animals. To investigate the co-induced toxic effects of Mo and Cd on oxidative damage and kidney apoptosis in duck, 120 ducks were randomly divided into control group and 5 treatment groups which were treated with a commercial diet containing different dosages of Mo and Cd. Kidney samples were collected on the 60th and 120th days to determine the mRNA expression levels of ceruloplasmin (CP), metallothionein (MT), Bak-1, and Caspase-3 by quantitative RT-PCR. Additionally, we also determined the antioxidant activity indexes and contents of Mo, Cd, copper (Cu), iron (Fe), zinc (Zn), and selenium (Se) in serum. Meanwhile, ultrastructural changes of the kidney were observed. The results showed that glutathione reductase (GR) activity and CP level in serum were decreased in combination groups. In addition, the antioxidant indexes were decreased in co-treated groups compared with single treated groups. The mRNA expression levels of Bak-1 and Caspase-3 increased in co-treated groups. The mRNA expression level of CP in high-dose combination group was downregulated, while the mRNA expression of MT was upregulated except for low-dose Mo group. Additionally, in the later period the content of Cu in serum decreased in joint groups while the contents of Mo and Cd increased. In addition, ultrastructural changes showed mitochondrial crest fracture, swelling, deformed nuclei, and karyopyknosis in co-treated groups. Taken together, it was suggested that dietary Mo and Cd might lead to oxidative stress, kidney apoptosis and disturb homeostasis of trace elements in duck, and it showed a possible synergistic relationship between the two elements.

Applying Cadmium Relative Bioavailability to Assess Dietary Intake from Rice to Predict Cadmium Urinary Excretion in Nonsmokers.

Dietary Cd intake is often estimated without considering Cd bioavailability. Measured urinary Cd for a cohort of 119 nonsmokers with rice as a staple was compared to predicted values from rice-Cd intake with and without considering Cd relative bioavailability (RBA) in rice based on a steady state mouse kidney bioassay and toxicokinetic model. The geometric mean (GM) of urinary Cd and β2-microglobulin was 1.08 and 234 μg g-1 creatinine. Applying Cd-RBA in foods to aggregate Cd intake (41.5 ± 12.4, 48.0 ± 9.3, 48.8 ± 21.3% for rice, wheat, and vegetables), rice was the largest contributor (71%). For 63 participants providing paired urine and rice samples, the predicted GM of urinary Cd at 4.14 μg g-1 based on total Cd in rice was 3.5 times that of measured value at 1.20 μg g-1, while incorporating Cd-RBA to assess rice-Cd intake made the two closer with GM at 1.07 μg g-1. The cohort findings were extended to a national scale, with urinary Cd for nonsmokers from rice Cd intake was mapped at province/city levels after considering rice Cd-RBA. Therefore, incorporating Cd bioavailability to assess dietary Cd intake is a valuable tool to accurately estimate human Cd exposure and associated health risk.

Effect of cadmium on cytosine hydroxymethylation in gastropod hepatopancreas.

5-Hydroxymethylcytosine (5hmC) is an important, yet poorly understood epigenetic DNA modification, especially in invertebrates. Aberrant genome-wide 5hmC levels have been associated with cadmium (Cd) exposure in humans, but such information is lacking for invertebrate bioindicators. Here, we aimed to determine whether this epigenetic mark is present in DNA of the hepatopancreas of the land snail Cantareus aspersus and is responsive to Cd exposure. Adult snails were reared under laboratory conditions and exposed to graded amounts of dietary cadmium for 14days. Weight gain was used as a sublethal endpoint, whereas survival as a lethal endpoint. Our results are the first to provide evidence for the presence of 5hmC in DNA of terrestrial mollusks; 5hmC levels are generally low with the measured values falling below 0.03%. This is also the first study to investigate the interplay of Cd with DNA hydroxymethylation levels in a non-human animal study system. Cadmium retention in the hepatopancreas of C. aspersus increased from a dietary Cd dose of 1milligram per kilogram dry weight (mg/kg d. wt). For the same treatment, we identified the only significant elevation in percentage of samples with detectable 5hmC levels despite the lack of significant mortalities and changes in weight gain among treatment groups. These findings indicate that 5hmC is an epigenetic mark that may be responsive to Cd exposure, thereby opening a new aspect to invertebrate environmental epigenetics.

Cadmium stimulates myofibroblast differentiation and mouse lung fibrosis.

Increasing evidence suggests that Cd at levels found in the human diet can cause oxidative stress and activate redox-sensitive transcription factors in inflammatory signaling. Following inflammation, tissue repair often involves activation of redox-sensitive transcription factors in fibroblasts. In lungs, epithelial barrier remodeling is required to restore gas exchange and barrier function, and aberrant myofibroblast differentiation leads to pulmonary fibrosis. Contributions of exogenous exposures, such as dietary Cd, to pulmonary fibrosis remain incompletely defined. In the current study, we tested whether Cd activates fibrotic signaling in human fetal lung fibroblasts (HFLF) at micromolar and submicromolar Cd concentrations that do not cause cell death. Exposure of HFLF to low-dose Cd (≤1.0μM) caused an increase in stress fibers and increased protein levels of myofibroblast differentiation markers, including α-smooth muscle actin (α-SMA) and extra-domain-A-containing fibronectin (ED-A-FN). Assay of transcription factor (TF) activity using a 45-TF array showed that Cd increased activity of 12 TF, including SMAD2/3/4 (mothers against decapentaplegic homolog) signaling differentiation and fibrosis. Results were confirmed by real-time PCR and supported by increased expression of target genes of SMAD2/3/4. Immunocytochemistry of lungs of mice exposed to low-dose Cd (0.3 and 1.0mg/L in drinking water) showed increased α-SMA protein level with lung Cd accumulation similar to lung Cd in non-smoking humans. Together, the results show that relatively low Cd exposures stimulate pulmonary fibrotic signaling and myofibroblast differentiation by activating SMAD2/3/4-dependent signaling. The results indicate that dietary Cd intake could be an important variable contributing to pulmonary fibrosis in humans.

Effects of Cd2+ exposure on key life history traits and activities of four metabolic enzymes in Helicoverpa armigera (Lepidopteran: Noctuidae)

ABSTRACTCadmium (Cd) is a toxic non-essential element accumulated easily in living organisms due to its non-biodegradable nature. A slight increase in Cd levels will threaten the health of terrestrial and aquatic organisms. Therefore, Cd contamination and its effects on the ecosystems and organisms have become a major topic of eco-toxicological research. The present study investigated the eco-toxicological effects of Cd-supplemented diet on some life history traits and specific enzyme activities of carboxylesterase (CarE), glutathione S-transferase (GST), acetylcholinesterase (AChE) and cytochrome P450 monooxygenases (P450s) in the cotton bollworm, Helicoverpa armigera. The results showed that Cd significantly decreased larval survival, pupation and emergence, and reduced body mass of the sixth instar larvae, pupae, adult moths and female fecundity. Cd-supplemented diet also delayed the development of larvae and pupae and shortened the life span of the cotton bollworm moth. In addition, dietary Cd inhibited the activities of GST, CarE and P450, but increased AChE activity of the sixth instar larvae. We concluded that life history traits and metabolic enzymes are sensitive to Cd stress in the cotton bollworm. These parameters are potential biomarkers for monitoring environmental stress in Lepidopteran insect pests.

Health Risk Assessment of Dietary Cadmium Intake: Do Current Guidelines Indicate How Much is Safe?

Background:Cadmium (Cd), a food-chain contaminant, is a significant health hazard. The kidney is one of the primary sites of injury after chronic Cd exposure. Kidney-based risk assessment establishes the urinary Cd threshold at 5.24 μg/g creatinine, and tolerable dietary intake of Cd at 62 μg/day per 70-kg person. However, cohort studies show that dietary Cd intake below a threshold limit and that tolerable levels may increase the risk of death from cancer, cardiovascular disease, and Alzheimer’s disease.Objective:We evaluated if the current tolerable dietary Cd intake guideline and urinary Cd threshold limit provide sufficient health protection.Discussion:Staple foods constitute 40–60% of total dietary Cd intake by average consumers. Diets high in shellfish, crustaceans, mollusks, spinach, and offal add to dietary Cd sources. Modeling studies predict the current tolerable dietary intake corresponding to urinary Cd of 0.70–1.85 μg/g creatinine in men and 0.95–3.07 μg/g creatinine in women. Urinary Cd levels of < 1 μg/g creatinine were associated with progressive kidney dysfunction and peripheral vascular disease. A urinary Cd of 0.37 μg/g creatinine was associated with breast cancer, whereas dietary Cd of 16–31.5 μg/day was associated with 25–94% increase in risk of estrogen receptor–positive breast cancer.Conclusion:Modeling shows that dietary intake levels for Cd exceed the levels associated with kidney damage and many other adverse outcomes. Thus, the threshold level of urinary Cd should be re-evaluated. A more restrictive dietary intake guideline would afford enhanced health protection from this pervasive toxic metal.Citation:Satarug S, Vesey DA, Gobe GC. 2017. Health risk assessment of dietary cadmium intake: do current guidelines indicate how much is safe? Environ Health Perspect 125:284–288; http://dx.doi.org/10.1289/EHP108

The simultaneous uptake of dietary and waterborne Cd in gastrointestinal tracts of marine yellowstripe goby Mugilogobius chulae

Aquatic animals under waterborne metal exposure are also very likely exposed to elevated dietary metals. This study quantified the simultaneous uptake of dietary and waterborne Cd in gastrointestinal tracts (GT) of marine yellowstripe goby using a dual stable isotope tracer method. The Cd spiked diet (10–100 μg g−1, 111Cd as tracers) were fed to the fish as a single meal, and then the fish were exposed to waterborne Cd (0–500 μg L−1, 113Cd as tracers) for 48 h, during which the time-course uptake of Cd in the stomach and intestine was determined. The findings revealed that the dietary Cd uptake mainly occurred within 12 h after feeding. The fish exposed to 500 μg L−1 waterborne Cd showed significantly lower Cd assimilation efficiency (2.07%) than the control group (3.48%) at the dietary Cd of 100 μg g−1. Moreover, during 4–12 h when there was chyme in the GT, the waterborne Cd uptake in the intestine was lowest but the stomach showed the highest waterborne Cd uptake rate. The uptake of dietary and waterborne Cd, and the relative importance of dietary vs waterborne Cd was positively correlated with the Cd concentration in the chyme. Overall, this research demonstrated that there was interaction between dietary and waterborne Cd uptake in the GT of marine fish. The simultaneous uptake of metal from two routes is far more complex than the situation of a single route of metal uptake, which should be evaluated in determining metal bioaccumulation and toxicity in both laboratory and field metal exposure scenario.

Diet-induced modifications to milk composition have long-term effects on offspring growth in rabbits.

It has been clearly demonstrated that the maternal nutritional status during pregnancy and lactation has long-term effects on offspring health. In mammals, milk represents the first maternal support provided to the newborns so that its composition may play a major role in long-term programming. We therefore assessed the effects of maternal high-fat/high-sugar obesogenic (OD) or control (CD) diets on offspring growth and adiposity in the rabbit. Between 7 and 20 wk of age, the BW gain of OD milk-fed rabbits was higher than that of CD milk-fed rabbits ( < 0.05). Body fat mass measurements at 21 wk of age revealed a significant increase in body adiposity as a function of milk ingested during the neonatal period, in both female and male offspring ( < 0.05). A marked weight gain difference was observed according to the milk in both female and male offspring. Moreover, we investigated the composition in major proteins and leptin levels in milk from OD or CD diet-fed dams. Liquid chromatography-mass spectrometry analysis of individual CD skimmed milk samples enabled identification and quantification of the rabbit main milk proteins and of their main phosphorylated isoforms at 2 different stages of lactation (3 and 10 d). Here we show that the OD diet induced a reduction in the whey acidic protein content concomitantly with both an increase in serum albumin and lactoferrin contents and in the phosphorylated isoforms of the main milk proteins. Furthermore, a sharp rise in leptin levels was observed in the milk of OD diet-fed dams on Day 10 of lactation when compared with CD diet animals ( < 0.05). Taken together, these findings provide evidence that lactation is a critical window of development during which exposure to a deleterious diet is highly detrimental to long-term outcomes. Moreover, these insights suggest that it may be possible to prevent at least some of the adverse effects of inadequate maternal nutrition on the long-term metabolic outcomes of the offspring through nutritional interventions applied during the lactation period.

Kidney Cadmium Toxicity, Diabetes and High Blood Pressure: The Perfect Storm.

Cadmium (Cd) is an environmental toxicant of widespread exposure and pervasive toxicity. Absorption, systemic transport and uptake of Cd are mediated by metal transporters that the body uses for acquisition of physiologically-essential elements, notably of iron, zinc and calcium. Currently, human exposure to Cd is known to damage the kidneys, especially the proximal tubular cells that actively reabsorb Cd along with zinc, glucose and amino acids in the glomerular filtrate. Severe kidney damage, glycosuria and proteinuria are known outcomes after high dietary Cd intake (> 200 µg/day). Dietary Cd intake of 10-30 µg/day has been linked with reduced tubular reabsorption, chronic kidney disease, hypertension, coronary arterial and peripheral arterial diseases, macular degeneration, obesity-independent diabetes, and cancer. The links between diabetes, hypertension and end stage kidney disease (ESKD) are indisputable. ESKD requires dialysis or kidney transplant, an immense health care cost. This review adds to these connections by presenting the synergism of kidney Cd toxicity on blood pressure control and glucose homeostasis. Blood pressure control is mediated at least in part by cytochrome P450 (CYP) enzymes such as CYP4A11 and CYP4F2 that produce 20-hydroxyeicosatetraenoic acid (20-HETE), involved in salt balance in the kidney, and all are known to be altered during Cd exposure. The potential effects of Cd exposure on glucose reabsorption, inflammation, oxidative stress, and heme oxygenase activity are highlighted. The information presented offers strategies for mitigation of toxic effects of Cd through minimization of the food-chain transfer of Cd, and modulation of mechanistic pathways altered by Cd exposure.

Banana Blossom (Musa acuminate Colla) Incorporated Experimental Diets Modulate Serum Cholesterol and Serum Glucose Level in Wistar Rats Fed with Cholesterol.

Hypocholesterolaemic and hypoglycaemic effect of banana blossom were studied in high-cholesterol fed rats. Experimental groups were fed for 4 weeks, with casein as the basal diet (CN), in comparison with two diets containing 0.5% cholesterol (CD) and 0.5% cholesterol + 21% banana blossom powder (CDB). Serum total cholesterol, non-HDL-cholesterol level, and serum glucose concentrations were lower in CDB fed group compared with CD fed group. Lower serum cholesterol and glucose level (P < 0.05) in CDB fed group were followed by higher faecal weight, caecal weight, caecal Lactobacilli, and Bifidobacteria population in CDB fed group compared to CD diet fed group. Lower serum AST level in banana blossom fed rats showed the reduction in oxidative stress induced by high cholesterol diet. Based on these data, it could be speculated that banana blossom incorporated experimental diets may modulate the hypocholesterolaemic and hypoglycaemic responses in Wistar rats.

94 - Lung Cysteine/cystine Redox Potential Increase Is Associated with Worse Inflammation and Disrupted Metabolism during H1N1 Infection and Exposure to Dietary Levels of Cadmium

Influenza A virus subtype H1N1 is seasonally active in the United States, affecting millions of people each year and claiming tens of thousands of lives since the 2009 pandemic. Public health efforts have focused on vaccination, but exposed individuals who become sick face severe inflammation and possibly death. Cadmium (Cd) is a ubiquitous heavy metal that interacts with thiols such as metallothionein and GSH. Public dietary exposure has remained steadily constant, potentially worsening health risks. Emerging evidence suggests Cd may worsen lung disease at levels achievable in the diet. To assess the role of dietary Cd in lung inflammation, mice were exposed to 1 mg/l CdCl 2 in drinking water for 16 weeks. 10 days prior to study completion, mice were intranasally given sub-lethal H1N1 or sterile saline. H1N1 caused a 20% body weight loss and 7-fold increase in airway enhanced pause after 10 days, and Cd exposure caused a 4.8-fold increase in lung tissue Cd without detectable changes in urine or plasma. Infected and Cd-exposed mice had worse lung inflammation, which was comprised of neutrophils, monocytes and T cells, and increased KC, IP-10, IFN-γ and IL-6. Lung tissue cysteine/cystine redox potential (Eh[CySS]) was progressively increased by Cd, H1N1 and the combination, unlike glutathione redox potential (Eh[GSSG]). A similar, less significant trend was observed in plasma Eh[GSSG]. Reducing Eh[CySS] clustered with myogenesis and complement pathway genes by associating with inflammation-sensitive metabolism such as kynurenine conversion to anthranilic acid. These data suggest lung Eh[CySS] coordinates tissue responses to viral-induced inflammation and that ingested Cd may significantly worsen lung inflammation during respiratory infections.

64 - Low Dose Cadmium Stimulates Myofibroblast Differentiation and Lung Fibrosis by Activation of SMAD and Nuclear Thioredoxin-1

Background Toxic effects of cadmium (Cd) from cigarette smoke and occupational sources are well studied, yet low-level Cd also occurs in human diet. Cd accumulates in vivo due to a twenty-year biological half-life. Increasing evidence suggests that exposure to dietary Cd can impact human health by potentiating inflammatory mechanism. Submicromolar Cd can alter cellular redox control mechanism, contributing to stimulation of pulmonary diseases. The pathogenesis of idiopathic pulmonary fibrosis involves excessive myofibroblast activation which leads to increased contractures in lung. Substantial evidence supports that myofibroblast differentiation is associated with disruption of redox homeostasis, yet the mechanistic effects of exogenous exposure remains unknown. Objectives To test our hypothesis that low dietary levels of Cd stimulate pulmonary fibrosis via activation of SMAD transcription factor and stimulation of myofibroblast differentiation. Results Using human fetal lung fibroblasts (HFLF), we found that two differentiation markers, α-Smooth-Muscle-actin (α-SM-actin) and Extra-Domain-A-containing fibronectin (ED-A FN), were significantly elevated in transcriptional and translational levels by low-dose Cd (0.5, 1.0 and 2.0 μM). Under the same Cd treatment, an increased formation of stress fibers was observed in HFLF. To examine the effects of low-dose Cd on SMAD activation and redox regulatory mechanism, HFLF was transfected with nuclear exporting or nuclear localized signal conjugated thioredoxin (Trx)-1 to express in cytoplasm or nucleus, respectively. The results show that Cd increased SMAD activity by 3 fold and stimulated translocation of Trx1 from cytoplasm to nucleus. Overexpression of Trx1 in cytoplasm diminished Cd induced SMAD activation, while overexpression of Trx1 in nuclei mimicked the Cd effect. This suggests that low-dose Cd stimulates differentiation of HFLF to myofibroblast by mechanism involving nuclear translocation of Trx1 followed by activation of SMAD and subsequent gene expression of α-SM-actin and ED-A FN for differentiation and fibrosis. Conclusion Low dietary exposure to Cd presents a potential risk for pulmonary fibrosis by affecting redox signaling mechanism. The improved understanding of redox regulation mechanism in differentiation and fibrosis can provide therapeutic targets to maintain pulmonary health.

Genetic Diversity, Rather than Cultivar Type, Determines Relative Grain Cd Accumulation in Hybrid Rice.

Cadmium (Cd) is a toxic element, and rice is known to be a leading source of dietary Cd for people who consume rice as their main caloric resource. Hybrid rice has dominated rice production in southern China and has been adopted worldwide. The characteristics of high yield heterosis of rice hybrids makes the public think intuitively that the hybrid rice accumulates more Cd in grain than do inbred cultivars. A detailed understanding of the genetic basis of grain Cd accumulation in hybrids and developing Cd-safe rice are one of the top priorities for hybrid rice breeders at present. In this study, we investigated genetic diversity and grain Cd levels in 617 elite rice hybrids collected from the middle and lower Yangtze River Valley in China and 68 inbred cultivars from around the world. We found that there are large variations in grain Cd accumulation in both the hybrids and their inbred counterparts. However, we found grain Cd levels in the rice hybrids to be similar to the levels in indica rice inbreds, suggesting that the hybrids do not accumulate more Cd than do the inbred rice cultivars. Further analysis revealed that the high heritability of Cd accumulation in the grain and the single indica population structure increases the risk of Cd over-accumulation in hybrid rice. The genetic effects of Cd-related QTLs, which have been identified in related Cd-QTL mapping studies, were also determined in the hybrid rice population. Four QTLs were identified as being associated with the variation in grain Cd levels; three of these loci exhibited obvious indica-japonica differentiations. Our study will provide a better understanding of grain Cd accumulations in hybrid rice, and pave the way toward effective breeding for high-yielding, low grain-Cd hybrids in the future.

Biological transfer of dietary cadmium in relation to nitrogen transfer and 15N fractionation in a soil collembolan-predatory mite food chain

Effects of cadmium (Cd) on collembolans and predatory mites have been well studied but Cd accumulation and biological transfer and the relationship between Cd trophic transfer and nitrogen (N) isotope fractionation and transfer in soil micro-arthropod food chains remain poorly understood. Here, we investigated the biological transfer and trophic toxicity of Cd and the effects of dietary Cd exposure on 15N fractionation in animal tissues and N transfer from food in a soil collembolan (Folsomia candida)-predatory mite (Hypoaspis aculeifer) food chain using experiments conducted in plate and soil systems. Synchronized F. candida were fed yeast or wheat spiked with 0 (Control), 50 (Cd50), 100 (Cd100) or 200 (Cd200) μg Cd g−1 food for two weeks and were then offered to synchronized H. aculeifer as prey for two weeks. Cadmium concentrations in tissues of both the collembolan and its predator increased as the Cd concentrations in the food yeast or wheat increased in both the plate and soil systems, and the Cd concentrations in the food and the animals were all significantly and positively correlated. Except for the controls, the Cd bioaccumulation factor (BAF) between adults of predatory mites and consumer collembolans (0.20–1.13) was 2.5–14 times higher than that from food yeast/wheat to consumer collembolans (0.02–0.08). Cadmium transfer has not altered the reproduction of the filial generation collembolans but the reproduction of the predatory mite declined by 34.3% with the Cd concentration in its juveniles reaching 5.94 μg g−1, suggesting that Cd transfer from the spiked food can present a higher toxicity to the predator H. aculeifer. Food spiked with Cd decreased the N content in the collembolan tissues assimilated from the food and enriched the 15N fraction (δ15N) in their tissues by affecting their metabolic turnover and growth rates. The Cd trophic transfer between collembolans and predatory mites from spiked food can directly increase the δ15N value of predatory mites and restrict the movement of N from collembolans to predatory mites. The δ15N of soil animals has considerable potential as a biomarker of Cd stress, 15N isotope application may be limited in Cd polluted soil ecosystems, and the N transfer function of soil food webs may be more vulnerable in polluted ecosystems.

Long-term effects of perinatal exposure to low doses of cadmium on the prostate of adult male rats.

Developmental toxicity caused by environmental exposure to heavy metals during the perinatal period has raised questions about offspring health. Cadmium (Cd) is an endocrine-disrupting chemical with the potential to interfere with morphogenesis and susceptibility to diseases in reproductive organs. Taking into account that in the rat prostate morphogenesis occurs during the perinatal period, and that pregnant females absorb and retain more dietary Cd than their non-pregnant counterparts, it is important to understand the effects of perinatal Cd exposure on the adult rat prostate. Therefore this study investigated the effects of gestational and lactational Cd exposure on adult offspring rat prostate histopathology. Pregnant rats (n=20) were divided into two groups: Control (treated with aqueous solution of sodium acetate 10mg/l) and treated (treated with aqueous solution of cadmium acetate 10mg/l) administered in the drinking water. After weaning, male offspring from different litters (n=10) received food and water 'adlibitum'. The animals were euthanized at postnatal day 90 (PND90), the ventral prostates (VPs) were removed, weighed and examined histopathologically. Blood was collected for the measurement of testosterone (T) levels. Immunohistochemistry for androgen receptor (AR) and Ki67, and a TUNEL assay were performed. There were no differences in T levels, cell proliferation and apoptosis indexes, or AR immunostaining between the experimental groups. Stromal inflammatory foci and multifocal inflammation increased significantly in the treated group. These changes were associated with inflammatory reactive epithelial atypia and stromal fibrillar rearrangement. In conclusion, VP was permanently affected by perinatal Cd exposition, with increased incidence of inflammatory disorders with ageing.

Low-dose oral cadmium increases airway reactivity and lung neuronal gene expression in mice.

Inhalation of cadmium (Cd) is associated with lung diseases, but less is known concerning pulmonary effects of Cd found in the diet. Cd has a decades‐long half‐life in humans and significant bioaccumulation occurs with chronic dietary intake. We exposed mice to low‐dose CdCl2 (10 mg/L in drinking water) for 20 weeks, which increased lung Cd to a level similar to that of nonoccupationally exposed adult humans. Cd‐treated mice had increased airway hyperresponsiveness to methacholine challenge, and gene expression array showed that Cd altered the abundance of 443 mRNA transcripts in mouse lung. In contrast to higher doses, low‐dose Cd did not elicit increased metallothionein transcripts in lung. To identify pathways most affected by Cd, gene set enrichment of transcripts was analyzed. Results showed that major inducible targets of low‐dose Cd were neuronal receptors represented by enriched olfactory, glutamatergic, cholinergic, and serotonergic gene sets. Olfactory receptors regulate chemosensory function and airway hypersensitivity, and these gene sets were the most enriched. Targeted metabolomics analysis showed that Cd treatment also increased metabolites in pathways of glutamatergic (glutamate), serotonergic (tryptophan), cholinergic (choline), and catecholaminergic (tyrosine) receptors in the lung tissue. Protein abundance measurements showed that the glutamate receptor GRIN2A was increased in mouse lung tissue. Together, these results show that in mice, oral low‐dose Cd increased lung Cd to levels comparable to humans, increased airway hyperresponsiveness and disrupted neuronal pathways regulating bronchial tone. Therefore, dietary Cd may promote or worsen airway hyperresponsiveness in multiple lung diseases including asthma.