The Effect of L-Carnitine on Cadmium Toxicity in Liver and Kidney Tissue in Prepubertal Female Rats

SUMMARY: Cadmium (Cd) is a toxic element that accumulates in kidney and liver. L-carnitine(LC) is a natural compound that has been shown to exhibit antioxidant activity. Aim of this study was to investigate the effect of L-carnitine against cadmium-induced changes in liver and kidney tissues in prepubertal female rats. In this study 21-day-old female Wistar Albino rats were used. Control, cadmium (2 mg/kg cadmium intraperitoneally), L-carnitine (300 mg/kg orally) and cadmium+L-carnitine groups were formed. Liver and kidney tissue sections were stained with Hematoxylin-Eosin and Masson Trichrome. Histological scoring was performed in liver and kidney. In the liver tissue given Cd, bile duct proliferation, inflammation cells and connective tissue in the portal area were decreased in treatment group. In kidneys, cadmium group treated with L-carnitine, it was observed that the capillary congestion in the kidneys decreased, but tubular dilatation continued in some places. In fibrosis scoring of the liver groups,statistically significant decrease was observed in the Cd+LC group compared to group of cadmium. In the histological scoring results of the kidney groups, statistically significant decrease in congestion and tubular epithelial degeneration was observed in the group treated with L-carnitine compared to group with cadmium. In conclusion medium-dose cadmium has toxic effects in liver and kidney of prepubertal female rats in subacute period,these effects are alleviated with L-carnitine.

El cadmio (Cd) es un elemento tóxico que se acumula en los riñones y el hígado. La L-carnitina (LC) es un compuesto natural que ha demostrado tener actividad antioxidante. El objetivo de este estudio fue investigar el efecto de la L-carnitina contra los cambios inducidos por el cadmio en los tejidos del hígado y el riñón en ratas hembra prepúberes. En este estudio se utilizaron ratas Wistar Albinas hembra de 21 días de edad. Se formaron grupos control, cadmio (2 mg/kg de cadmio por vía intraperitoneal), L- carnitina (300 mg/kg por vía oral) y cadmio + L-carnitina. Se tiñeron secciones de tejido de hígado y riñón con Hematoxilina-Eosina y tricrómico de Masson. La puntuación histológica se realizó en hígado y riñón. En el tejido hepático que recibió Cd, la proliferación de los conductos biliares, las células inflamatorias y el tejido conectivo en el área portal disminuyeron en el grupo con tratamiento. En los riñones, en el grupo de cadmio tratado con L- carnitina, se observó que la congestión capilar disminuyó, pero la dilatación tubular continuó en algunos sitios. En la puntuación de fibrosis de los grupos de hígado, se observó una disminución estadísticamente significativa en el grupo de Cd+LC en comparación con el grupo de cadmio. Los resultados de puntuación histológica de los grupos de riñón, arrojó una disminución estadísticamente significativa en la congestión y el epitelio tubular Se observó degeneración en el grupo tratado con L-carnitina en comparación con el grupo con cadmio. En conclusión, las dosis medias de cadmio tienen efectos tóxicos en el hígado y los riñones de ratas hembras prepúberes en el período subagudo; estos efectos se alivian con L-carnitina.

Cadmium toxicity symptoms and uptake mechanism in plants: a review / Sintomas de toxicidade de cádmio e mecanismo de absorção em plantas: uma revisão

Cadmium (Cd) is one of non-essential heavy metals which is released into environment naturally or anthropogenically. It is highly persistent toxic metals that are exceptionally distressing industrial and agriculture activities by contaminating soil, water and food. Its long-duration endurance in soil and water results in accumulation and uptake into plants, leading to the food chain. This becomes a serious global problem threatening humans and animals as food chain components. Living organisms, especially humans, are exposed to Cd through plants as one of the main vegetative food sources. This review paper is concentrated on the symptoms of the plants affected by Cd toxicity. The absorption of Cd triggers several seen and unseen symptoms by polluted plants such as stunted growth, chlorosis, necrosis and wilting. Apart from that, factors that affect the uptake and translocation of Cd in plants are elaborated to understand the mechanism that contributes to its accumulation. By insight of Cd accumulation, this review also discussed the phytoremediation techniques-phytoextraction, phytostimulation, phytostabilization, phytovolatization and rhizofiltration in bioremediating the Cd.

O cádmio (Cd) é um dos metais pesados ​​não essenciais que é liberado no meio ambiente de forma natural ou antropogênica. São metais tóxicos altamente persistentes que prejudicam excepcionalmente as atividades industriais e agrícolas, contaminando o solo, a água e os alimentos. Sua resistência de longa duração no solo e na água resulta em acúmulo e absorção pelas plantas, levando à cadeia alimentar. Isso se torna um sério problema global que ameaça humanos e animais como componentes da cadeia alimentar. Os organismos vivos, principalmente os humanos, são expostos ao Cd através das plantas como uma das principais fontes de alimento vegetativo. Este artigo de revisão concentra-se nos sintomas das plantas afetadas pela toxicidade do Cd. A absorção de Cd desencadeia vários sintomas visíveis e invisíveis por plantas poluídas, como crescimento atrofiado, clorose, necrose e murcha. Além disso, são elaborados fatores que afetam a absorção e translocação de Cd nas plantas para entender o mecanismo que contribui para o seu acúmulo. A partir do conhecimento do acúmulo de Cd, esta revisão também discutiu as técnicas de fitorremediação - fitoextração, fitoestimulação, fitoestabilização, fitovolatização e rizofiltração na biorremediação do Cd.

Cadmium toxicity symptoms and uptake mechanism in plants: a review

Abstract Cadmium (Cd) is one of non-essential heavy metals which is released into environment naturally or anthropogenically. It is highly persistent toxic metals that are exceptionally distressing industrial and agriculture activities by contaminating soil, water and food. Its long-duration endurance in soil and water results in accumulation and uptake into plants, leading to the food chain. This becomes a serious global problem threatening humans and animals as food chain components. Living organisms, especially humans, are exposed to Cd through plants as one of the main vegetative food sources. This review paper is concentrated on the symptoms of the plants affected by Cd toxicity. The absorption of Cd triggers several seen and unseen symptoms by polluted plants such as stunted growth, chlorosis, necrosis and wilting. Apart from that, factors that affect the uptake and translocation of Cd in plants are elaborated to understand the mechanism that contributes to its accumulation. By insight of Cd accumulation, this review also discussed the phytoremediation techniques-phytoextraction, phytostimulation, phytostabilization, phytovolatization and rhizofiltration in bioremediating the Cd.

Resumo O cádmio (Cd) é um dos metais pesados não essenciais que é liberado no meio ambiente de forma natural ou antropogênica. São metais tóxicos altamente persistentes que prejudicam excepcionalmente as atividades industriais e agrícolas, contaminando o solo, a água e os alimentos. Sua resistência de longa duração no solo e na água resulta em acúmulo e absorção pelas plantas, levando à cadeia alimentar. Isso se torna um sério problema global que ameaça humanos e animais como componentes da cadeia alimentar. Os organismos vivos, principalmente os humanos, são expostos ao Cd através das plantas como uma das principais fontes de alimento vegetativo. Este artigo de revisão concentra-se nos sintomas das plantas afetadas pela toxicidade do Cd. A absorção de Cd desencadeia vários sintomas visíveis e invisíveis por plantas poluídas, como crescimento atrofiado, clorose, necrose e murcha. Além disso, são elaborados fatores que afetam a absorção e translocação de Cd nas plantas para entender o mecanismo que contribui para o seu acúmulo. A partir do conhecimento do acúmulo de Cd, esta revisão também discutiu as técnicas de fitorremediação - fitoextração, fitoestimulação, fitoestabilização, fitovolatização e rizofiltração na biorremediação do Cd.

Hepatic lipidomics study in chronic cadmium-exposed mice / 局解手术学杂志

Objective To study the change of lipidomics in chronic cadmium-exposed mice,thereby screening out lipid subclasses,lipid molecules and enriched metabolic pathways with significant differences.Methods Twelve SPF male C57BL/6J mice(8 weeks old)were randomly divided into the control group(normal water feeding)and the experimental group[cadmium water(0.6 mg/L of CdCl2)feeding],with 6 mice in each group.Mice were sacrificed after 6 months of cadmium exposure,and fresh liver tissues were collected immediately.Lipid oil red O staining and lipidomics analysis were performed on liver tissue.Results Compared with the control group,the liver tissue of mice in the experimental group did not appear red after lipid oil red O staining.Seventeen lipid subclasses with significant differences and 144 lipid molecules with significant differences were screened out by lipidomics.These lipid molecules with significant differences were enriched in glycerophospholipid metabolism,linoleic acid metabolism,alpha-linolenic acid metabolism,glycosylphosphati-dylinositol biosynthesis,glycerolipid metabolism and arachidonic acid metabolism by KEGG.Conclusion This study reveals that chronic cadmium exposure can induce the disorder of lipid subclasses and lipid metabolites in the liver of mice,which provides a basis for understanding the non-alcoholic fatty liver disease caused by chronic cadmium exposure.

Risk assessment of cadmium exposure of Shanghai residents based on different dietary exposure assessment methods / 上海预防医学

ObjectiveTo conduct comprehensive assessment of internal and external cadmium exposure and health risks for Shanghai residents. MethodsCadmium levels in food samples were calculated by employing two dietary exposure assessment methods， total diet study （TDS） and food frequency questionnaire （FFQ）， to estimate the daily dietary cadmium exposure of Shanghai residents. The provisional tolerable monthly intake （PTMI） of cadmium set by joint food and agriculture organization/WHO expert committee on food additives （JECFA） was applied to evaluate the health risk. Differences in dietary and urinary cadmium were compared by rank-sum test among different regions， age， gender， smoking status， and BMI groups， and the association between internal and external cadmium exposure was investigated by correlation analysis. ResultsThe mean value of urinary cadmium for 1 300 respondents was 0.542 μg·L-1. Urinary cadmium was higher in the population in central urban and urban-rural fringe areas than in the suburban area， higher in the older age group than in the younger age group， and higher in the smoking group than in the non-smoking group （all P<0.01）. The two assessment methods showed that the mean values of daily dietary cadmium exposure for Shanghai residents were 0.306 and 0.090 μg·kg-1， with 3.69% and 0.85% of Shanghai residents exceeding the PTMI， respectively. Correlation analyses showed that dietary exposure to cadmium based on the FFQ method was positively correlated with the urinary cadmium level when smoking status， age， gender， and BMI were adjusted. ConclusionDietary exposure to cadmium of Shanghai residents is mainly derived from vegetables， aquatic products， cereals and potatoes， and is overall at a low-risk level. Dietary exposure assessment based on FFQ and risk monitoring data can effectively estimate long-term cadmium exposure.

Relative bioavailability of cadmium in aquatic products and its application on the cadmium exposure risk assessment / 上海预防医学

ObjectiveTo understand the relative bioavailability （RBA） of cadmium in different aquatic products. Based on the consideration of the gender differences and the relative bioavailability of cadmium in different foods， the physiologically based toxicokinetic （PBTK） model of cadmium was further optimized and verified. The correlation between internal and external exposure in quantitative risk assessment of food safety was optimized， and the provisional tolerable daily intake （PTDI） value of cadmium was derived. MethodsThe relative bioavailability of cadmium in different aquatic products was determined in four-week-old Balb/c female mice. The PBTK model of cadmium metabolism was optimized by ABC-MCMC method using combined internal and external exposure data of cadmium in Shanghai residents， and the PTDI was calculated accordingly. ResultsExcept for scallops and squid， the RBA of aquatic samples was less than 1， indicating that the absorption rate of cadmium in aquatic products was lower than that of cadmium chloride. The higher RBA of squid and scallop may be due to the presence of cadmium in the visceral organs， which is conducive to cadmium absorption and its higher concentration of cadmium. Frying at the temperature less than 160 ℃ reduced cadmium absorption but may increase cadmium absorption at the temperature greater than 160 ℃. The optimized model parameters converged well and the model could reasonably estimate urinary cadmium level according to the external exposure of cadmium. The PTDI value was0.466 4 μg·（kg·day）-1 according to the optimized single-chamber model. ConclusionThe relative bioavailability of cadmium in different foods varies greatly， except for squid and scallops， RBA is less than 1， and cooking processing will affect the RBA of food. The construction of the PBTK model did not only consider the effects of gender differences on cadmium metabolism， but also included the relative bioavailability data to optimize and adjust the correlation coefficient of absorption rate. Compared with the model without RBA adjustment， the adjusted model has enhanced the ability to predict urinary cadmium level， which provides a new， more accurate method for the risk assessment of food safety.

Mechanisms of male reproductive function damage induced by heavy metal cadmium / 实用医学杂志

Cadmium is one of the heavy metals with severe reproductive toxicity,whose half-life lasts 20 to 40 years.Cadmium could induce dysfunction of testis and epididymis for its significant accumulation in human testis,and the amount,motility parameters and morphology of sperm change abnormally.The adverse change could also extend to male offspring and cause the impairment of their reproductive system.There has been no clear mecha-nism of how cadmium induces dysfunction of male reproductive system,and treatment for the adverse influence on male reproductive system by cadmium has not yet been found.Therefore,this problem has been discussed in repro-ductive and environmental field for a long time.A number of previous investigations showed that cadmium could damage male fertility by followed pathways,including interfering with hormone secretion,inducing oxidative stress,activating inflammation and apoptosis,and causing energy metabolism disorder,etc.In order to enlighten new ideas for therapeutic targets of male reproductive function damage induced by cadmium,we systematically reviewed and summarized the findings of previous publications in this paper.

Cadmium promotes senescence of annulus fibrosus cells via activation of PI3K/Akt signaling pathway / 中国组织工程研究

BACKGROUND:Cadmium is a common environmental pollutant,which can damage multiple organs and tissues,such as the kidney and bone,but its effect on annulus fibrosus cells in the intervertebral disc has been less reported. OBJECTIVE:To investigate the effect of cadmium chloride on the senescence of annulus fibrosus cells and the role of PI3K/Akt signaling pathway. METHODS:Annulus fibrosus cells from Sprague-Dawley rat intervertebral discs were harvested and passage 3 cells were intervened with different concentrations of cadmium chloride(0,1,5,10,20 μmol/L).Cell viability and proliferation were detected by cell counting kit-8 assay.Transcriptome sequencing and Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis were performed on annulus fibrosus cells with or without cadmium chloride addition.Passage 3 annulus fibrosus cells were divided into control group,cadmium chloride group and LY294002 group.Cell proliferation rate was detected by EdU method,positive cell rate was detected by senescence-associated β-galactosidase staining,and expressions of senescence-associated proteins(p16,p21 and p53)and p-Akt at protein and mRNA levels were measured by western blot,RT-PCR and immunofluorescence. RESULTS AND CONCLUSION:5 μmol/L cadmium chloride could inhibit the proliferation of annulus fibrosus cells.Results from the Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis showed that the main signal transduction pathways included PI3K/Akt,cell cycle and p53 signaling pathways,which were related to cell senescence and proliferation.PI3K/Akt signaling pathways with significant differential expression were selected for validation.Compared with the control group,the EdU-positive rate was significantly decreased in the cadmium chloride group(P<0.05),while the β-galactosidase-positive rate,the expression of senescence-associated proteins(p16,p21 and p53)and p-Akt significantly increased(P<0.05).Compared with the cadmium chloride group,the EdU-positive rate and p-Akt expression were significantly decreased in the LY294002 group(P<0.05),while the β-galactosidase-positive rate and the expression of senescence-associated proteins(p16,p21 and p53)significantly increased(P<0.05).To conclude,cadmium chloride can regulate the senescence of annulus fibrosus cells by activating the PI3K/Akt signaling pathway,thereby inducing the occurrence and progression of intervertebral disc degeneration.

Research progress on cognitive dysfunction induced by occupational noise and combined exposure to heavy metals / 中国职业医学

Exposure to occupational noise and heavy metals are common occupational hazards in workplaces. Occupational noise exposure not only leads to noise-induced hearing loss but also cognitive dysfunction. Exposure to common heavy metals such as lead, manganese, and cadmium during work is closely related to cognitive dysfunction in workers. Combined exposure to noise and heavy metals is common in workplaces. However, current research on the combined effects of exposure to occupational noise with lead or manganese on workers' cognitive function is not comprehensive or systematic. The method for cognitive dysfunction identification varies, leading to a lack of comparability. And the causality between occupational exposure and cognitive dysfunction in workers has not been clarified. Therefore, studying the cognitive dysfunction due to combined exposure to noise and common heavy metals is of great significance for workers' occupational health. In the future, it is necessary to unify the method for cognitive dysfunction identification and conduct systematic and comprehensive research on the effects, mechanisms, and combined effects of exposure to occupational noise with lead, manganese, cadmium, and other heavy metals on workers' cognitive dysfunction, to ensure the occupational health rights and interests of workers.

Protective effect of 10-HDA on acute cadmium chloride-induced kidney damage and autophagy protein expression / 环境与职业医学

Background Acute cadmium (Cd) exposure can cause damage to multiple tissues, with the kidney being the primary target organ. The development of Cd-induced acute kidney injury involves complex mechanisms, in which autophagy and oxidative stress play crucial roles. Objective To investigate the effect of 10-hydroxy-2-decenoic acid (10-HDA) on kidney injury in mice exposed to cadmium, and provide experimental basis for studying the pathogenesis and prevention of Cd poisoning. Methods Thirty-five male C57BL/6 mice were divided into 7 groups (each of 5 mice): control group (normal saline, intraperitoneal injection), CdCl2 group (4 mg·kg−1, intraperitoneal injection), intervention groups ( 4 mg·kg−1 CdCl2, intraperitoneal Injection + 50, 100, 150, or 200 mg·kg−1 10-HDA, oral gavage), and 10-HDA group (150 mg·kg−1, oral gavage). All treatments were given for 14 d. Twenty-four hours after the last infection, physiological indicators [blood urea nitrogen (BUN), creatinine (CRE), malondialdehyde (MDA), and superoxide dismutase (SOD)], histopathological indicators, autophagy-related proteins (Atg7, Atg5, Beclin-1, and LC3), and mitochondrial autophagy-related proteins (PINK1 and Parkin) were detected to examine the effect of 10-HDA on kidney injury caused by CdCl2. Results Compared with the control group, the body weight of mice in the CdCl2 group was significantly reduced (P<0.01); compared with the CdCl2 group, the body weight of mice after intervention with different concentrations of 10-HDA was significantly increased (P<0.01). CdCl2 significantly increased BUN and CRE in the serum samples compared with the control group (P<0.01), which was significantly reduced to varying degrees after 100, 150, and 200 mg·kg−1 10-HDA intervention (P<0.01). MDA significantly increased and SOD significantly decreased in the renal cortex following CdCl2 administration compared with the control group (P<0.01), which was resolved following 10-HDA administration at different concentrations (P<0.01). In histopathological studies, 10-HDA restored injured kidney tissues induced by CdCl2. The expression levels of autophagy proteins Atg7 and LC3-II/I were significantly increased (P<0.05), and the expression level of Beclin-1 was significantly decreased (P<0.05) in the CdCl2 group compared with the control group. The expression levels of Atg7 were reduced to varying degrees after treatment with designed concentrations of 10-HDA, the expression levels of LC3-II/I were also reduced in the 50, 150, and 200 mg·kg−1 10-HDA intervention groups, and the expression levels of Beclin-1 were increased in the 50, 100, and 150 mg·kg−1 10-HDA intervention groups (P<0.05). The expression levels of PINK1 and Parkin in the CdCl2 group and the 50 mg·kg−1 10-HDA intervention group were lower than those in the control group (P<0.01). Compared with the CdCl2 group, the expression levels of PINK1 increased to varying degrees after 100, 150, and 200 mg·kg−1 10-HDA intervention, and the expression levels of Parkin increased in all 10-HDA intervention groups (P<0.01). Conclusion The intervention using 10-HDA can lessen acute kidney injury caused by CdCl2, reduce the expression of autophagy-related proteins, and increase the expression of mitochondrial autophagy-related proteins.

Does L-carnitine prevent cadmium-induced damage in gastrointestinal contractility and histological changes in prepubertal rat / ¿La L-carnitina previene el daño inducido por cadmio en la contractilidad gastrointestinal y los cambios histológicos en ratas prepúberes?

SUMMARY: Cadmium (Cd) is the industrial and environmental toxic heavy metal which is found in air, water and soil. Cd, adversely affects many organs in humans such as kidney, intestine, liver, testis and lungs. L-carnitine (LC) is an important agent that plays essential role in energy metabolism. In our study, we aimed to work out whether LC application has any protective effect on intestinal contractility and morphologic damage of prepubertal rat duodenum on Cd-induced toxicity. Twenty eight prepubertal female Wistar rats were divided into four groups. The first group is control (C), second group; Cd group; Cadmium chloride was given 2 mg/kg 28 days with a one-day break by i.p. The third group; Cd+LC, which cadmium chloride was given 2 mg/kg i.p. and LC was given orally by gastric lavage. The LC dose was given as 75 mg/kg. The fourth group; LC, which only LC was given orally. The intestinal segments were isolated and suspended in tissue bath. Contractile responses were induced by acetylcholine (ACh) and relaxation was achieved with phenylephrine. Also the segments were examined for histological changes by light microscopy. Ach-induced contractions were higher in Cd+LC, LC, and control group compared to the Cd group in duodenal segments. The phenylephrine-induced relaxations were lower in Cd groups as compared with Control, Cd+LC and LC group in duodenal segments. In Cd group intestinal morphology was observed to be severely damaged whereas in Cd+LC group the damage was noticeably lower. Cd administration caused severe cellular damage and decreased gastrointestinal motility. Treatment with the LC has affected the gastrointestinal contractility and reduced the damage in intestinal morphology, which occured after Cd application.

El cadmio (Cd) es el metal pesado tóxico industrial y ambiental que se encuentra en el aire, el agua y el suelo. El Cd afecta negativamente a muchos órganos humanos, como los riñones, los intestinos, el hígado, los testículos y los pulmones. La L-carnitina (LC) es un agente importante que juega un rol esencial en el metabolismo energético. El objetivo de este estudio fue determinar si la aplicación de LC tiene algún efecto protector sobre la contractilidad intestinal y el daño morfológico del duodeno de rata prepuberal sobre la toxicidad inducida por Cd. Veintiocho ratas Wistar hembras prepúberes se dividieron en cuatro grupos. El primer grupo control (C), segundo grupo; grupo cd; Se administró cloruro de cadmio 2 mg/kg durante 28 días con un descanso de un día por vía i.p. El tercer grupo; Cd+LC, al que se administró cloruro de cadmio 2 mg/kg i.p. y LC se administró por vía oral mediante lavado gástrico. La dosis de LC se administró como 75 mg/kg. El cuarto grupo; LC, al cual solo LC se administraba por vía oral. Los segmentos intestinales fueron aislados y suspendieron en baño de tejido. Las respuestas contráctiles fueron inducidas por acetilcolina (ACh) y la relajación se logró con fenilefrina. También se examinaron los segmentos en busca de cambios histológicos mediante microscopía óptica. Las contracciones inducidas por Ach fueron mayores en Cd+LC, LC y el grupo control en comparación con el grupo Cd en los segmentos duodenales. Las relajaciones inducidas por fenilefrina fueron menores en los grupos Cd en comparación con el grupo Control, Cd+LC y LC en los segmentos duodenales. En el grupo Cd se observó que la morfología intestinal estaba severamente dañada mientras que en el grupo Cd+LC el daño fue notablemente menor. La administración de Cd causó daño celular severo y disminución de la motilidad gastrointestinal. El tratamiento con LC afectó la contractilidad gastrointestinal y redujo el daño en la morfología intestinal, que ocurría después de la aplicación de Cd.

Network-based Toxicogenomics Approach to Unraveling the Influence of Lead and Cadmium Mixture on the Development and Progression of Hypertension

Heavy metals, generally characterized by high densities and atomic weights, are ubiquitous in the environment and are a public health concern due to the several health issues they pose to humans. Of all heavy metals, lead and cadmium among others are known to be capable of inducing multiple health effects even at a low rate of exposure. Hypertension (HYP), a major cause of death and a risk factor for other cardiovascular diseases, is known to be caused by both lead and cadmium. While the mechanism underlying the development of HYP induced by independent exposure to lead and cadmium has been well studied, the mechanism underlying the induction and progression of HYP upon lead and cadmium co-exposure remains mildly explored. Hence, this study aimed to elucidate the mechanism using a toxicogenomic approach. The set of genes affected by both heavy metals was identified using the comparative toxicogenomics database (CTD) while HYP targets were retrieved from the Gene Cards database. The shared genes between the heavy metals and the disease were identified and subjected to further analysis. The results of our analysis revealed the signaling pathways that are dysregulated by lead and cadmium co-exposure while oxidative stress, inflammation, and endothelial dysfunction were revealed as processes pertinent to the induction and progression of HYP by lead and cadmium co-exposure. Biomarkers that could be used for prognosis evaluation were also identified. Ultimately, this study supports and advances the growing body of finding on the roles played by lead and cadmium co-exposure in inducing HYP.

Metal Exposure in Arica, Chile: Examining Toxic Elements / Análisis de exposición a metales en Arica, Chile: niveles de elementos tóxicos

BACKGROUND: Bioaccumulation of toxic metals in the population is associated with adverse health effects. Although some elements are essential for humans, high levels of exposure can be dangerous. OBJECTIVE: To describe the levels of Inorganic Arsenic (AsIn), Cadmium (Cd), Chromium (Cr), and Mercury (Hg) in urine, and Lead (Pb) in blood in the population of Arica, Chile. METHODOLOGY: Descriptive study. Beneficiaries of the Health Surveillance Program of Law 20.590 in sites of higher risk of exposure in the commune of Arica were considered eligible. The results of biological samples to measure their concentrations of AsIn, Cd, Cr, Hg in urine, and Pb in blood between August 2016 and May 2021 are described. RESULTS: 9520 samples from a population with a mean age of 40.5 years were studied. 4.21% of the adult population and 6.57% of the children had AsIn values above 35 μg/L, while at least 95 % of the total samples had levels below 33 μg/L. At least 90 % of the samples had Cd levels below 1.1 μg/L, and 8.44 % had Cd levels above 2 μg/L, higher in males (11.67%). There were no values above the reference in children. 99.77% and 99.33% had Cr and Pb values below the reference limit, respectively (using the lowest reference range established by Chile Ministry of Health (MINSAL) < 5 μg/L). Children did not present risk values for Cr, and 0.16% presented Pb concentrations between 5-10 μg/dL. All samples presented Hg concentrations below risk levels (< 10 μg/L). CONCLUSIONS: The results of this study suggest that a small percentage of the samples analyzed in the beneficiary population of Arica register metal concentration levels above national reference levels established by MINSAL, mainly AsIn, Cd, and Pb. It is essential to continue biomonitoring to reduce and prevent exposure to these metals, which can have harmful effects on human health.

ANTECEDENTES: La bioacumulación de metales en la población está asociada a efectos adversos y pueden ser peligrosos. OBJETIVO: Describir los niveles de Arsénico Inorgánico (AsIn), Cadmio (Cd), Cromo (Cr), Mercurio (Hg) y Plomo (Pb) en la población de Arica, Chile. MATERIALES Y MÉTODOS: Estudio descriptivo. Se incluyeron todas las personas beneficiarias del Programa de Vigilancia de Salud de la Ley 20.590 en sitios de riesgo de mayor exposición en la comuna de Arica entre agosto 2016 y mayo 2021. RESULTADOS: Se estudiaron 9.520 muestras provenientes de una población con una edad media de 40.5 años. 4.21% de la población adulta y el 6.57% de los niños presentaron valores de AsIn superiores a 35 μg/L y al menos el 95% de las muestras totales tenía niveles inferiores a 33 μg/L. Más del 90 % de las muestras tuvieron niveles de Cd menores a 1.1 μg/L y un 8.44% registró niveles de Cd superiores 2 μg/L. El 99.77% y 99.33% exhibieron valores normales de Cr y Pb, respectivamente. Todas las muestras presentaron concentraciones de Hg por debajo de los niveles de riesgo (< 10 μg/L). CONCLUSIONES: Los resultados sugieren que un porcentaje pequeño de la población de Arica registra niveles de concentración de metales por sobre niveles de referencia nacional establecidos por el Ministerio de Salud de Chile, principalmente de AsIn, Cd y Pb. Es importante continuar con la vigilancia para reducir y prevenir la exposición a estos metales, que pueden generar efectos nocivos en la salud humana.

Exposição ao cádmio e Síndromes Hipertensivas da Gestação: uma revisão sistemática / Cadmium exposure and Hypertensive Disorders of Pregnancy: a systematic review

RESUMO As Síndromes Hipertensivas da Gestação (SHG) são uma das principais causas de morbimortalidade materna. Evidências crescentes indicam a associação entre a exposição ao cádmio e a hipertensão arterial na população em geral, mas não as SHG. Afim de investigar esse tema, realizou-se uma revisão sistemática seguindo as diretrizes PRISMA, nas bases de dados BVS/Lilacs, PubMed/Medline e SciELO e no repositório da Universidade de São Paulo (USP) até agosto de 2021. A qualidade metodológica foi avaliada pelo checklist Downs and Black. Selecionaram-se dezenove artigos, sendo treze caso-controle, quatro coortes e dois seccionais. No total, 11.451 participantes foram avaliadas, sendo 1.445 (12,6%) com SHG e, destas, 1.071 (74,1%) com pré-eclâmpsia. Observou-se o ajuste inadequado para confundimento em onze estudos. Dos sete estudos considerados de boa qualidade metodológica, quatro relataram associação positiva e três não a observaram, enquanto somente um estudo observou diferença de média, que foi maior nas gestantes com SHG. Atribuiu-se a divergência dos resultados às diferenças metodológicas e ao ajuste inadequado para os fatores de confusão. Como o cádmio é um metal tóxico que pode levar ao aumento do estresse oxidativo, que desempenha papel importante na fisiopatologia das SHG, estudos adicionais são necessários para elucidar esta associação.

ABSTRACT Hypertensive Disorders of Pregnancy (HDP) are one of the main causes of maternal morbimortality. Strong evidence point to an association between cadmium and hypertension in the general population, but not HDP. A systematic review was carried out to investigate this potential relationship, following PRISMA guidelines, in the BVS/LILACS, PubMed/MEDLINE, and SciELO databases and a repository (University of São Paulo - USP) until August 2021. The methodological quality was assessed using the Downs and Black checklist. Nineteen articles were selected, thirteen of which were case-control, four were cohorts, and two were cross-sectional. A total of 11.451 participants were evaluated, 1.445 (12.6%) with HDP, and of these 1.071 (74.1%) with preeclampsia. The inadequate adjustment for confounding was observed in eleven studies. Out of the seven studies considered good methodological quality, four reported a positive association, and three did not observe it. In contrast, only one observed a mean difference, which was higher in HDP. The inconsistency of the results was attributed to the methodological differences and inadequate adjustment for confounding. As cadmium is a toxic metal that can induce an increase in oxidative stress, which plays an essential role in the pathophysiology of HDP, additional studies are needed to elucidate this association.

Epidemiological research progress in the effects of metal exposure on kidney / 中南大学学报(医学版)

Chronic kidney disease (CKD) is suffered progressive loss of kidney function lasting more than 3 months and is classified according to the degree of kidney damage (level of proteinuria) and the decreased glomerular filtration rate (GFR). The most severe form of CKD is end-stage renal disease. The prevalence of CKD is high with fast growth rate and the disease burden has become increasingly serious. CKD has become an important public health problem threatening human health. The etiology of CKD is complex. In addition to genetic factors, environmental factors are an important cause of CKD. With the development of industrialization, environmental metal pollution has become increasingly severe, and its impact on human health has received widespread attention. A large number of studies have shown that metals such as lead, cadmium, and arsenic can accumulate in the kidney, which can cause damage to the structure and function of the kidney, and play an important role in the development of CKD. Therefore, summarizing the epidemiological research progress in the relationship between arsenic, cadmium, lead, and other metal exposures and kidney diseases can provide new ideas for the prevention and control of kidney diseases caused by metal exposure.

Potentilla anserina polysaccharide alleviates cadmium-induced oxidative stress and apoptosis of H9c2 cells by regulating the MG53-mediated RISK pathway / 中国天然药物

Oxidative stress plays a crucial role in cadmium (Cd)-induced myocardial injury. Mitsugumin 53 (MG53) and its mediated reperfusion injury salvage kinase (RISK) pathway have been demonstrated to be closely related to myocardial oxidative damage. Potentilla anserina L. polysaccharide (PAP) is a polysaccharide with antioxidant capacity, which exerts protective effect on Cd-induced damage. However, it remains unknown whether PAP can prevent and treat Cd-induced cardiomyocyte damages. The present study was desgined to explore the effect of PAP on Cd-induced damage in H9c2 cells based on MG53 and the mediated RISK pathway. For in vitro evaluation, cell viability and apoptosis rate were analyzed by CCK-8 assay and flow cytometry, respectively. Furthermore, oxidative stress was assessed by 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) staining and using superoxide dismutase (SOD), catalase (CAT), and glutathione/oxidized glutathione (GSH/GSSG) kits. The mitochondrial function was measured by JC-10 staining and ATP detection assay. Western blot was performed to detect the expression of proteins related to MG53, the RISK pathway, and apoptosis. The results indicated that Cd increased the levels of reactive oxygen species (ROS) in H9c2 cells. Cd decreased the activities of SOD and CAT and the ratio of GSH/GSSG, resulting in decreases in cell viability and increases in apoptosis. Interestingly, PAP reversed Cd-induced oxidative stress and cell apoptosis. Meanwhile, Cd reduced the expression of MG53 in H9c2 cells and inhibited the RISK pathway, which was mediated by decreasing the ratio of p-AktSer473/Akt, p-GSK3βSer9/GSK3β and p-ERK1/2/ERK1/2. In addition, Cd impaired mitochondrial function, which involved a reduction in ATP content and mitochondrial membrane potential (MMP), and an increase in the ratio of Bax/Bcl-2, cytoplasmic cytochrome c/mitochondrial cytochrome c, and Cleaved-Caspase 3/Pro-Caspase 3. Importantly, PAP alleviated Cd-induced MG53 reduction, activated the RISK pathway, and reduced mitochondrial damage. Interestingly, knockdown of MG53 or inhibition of the RISK pathway attenuated the protective effect of PAP in Cd-induced H9c2 cells. In sum, PAP reduces Cd-induced damage in H9c2 cells, which is mediated by increasing MG53 expression and activating the RISK pathway.

Physiological and biochemical mechanisms of brassinosteroid in improving anti-cadmium stress ability of Panax notoginseng / 中国中药杂志

In this study, the effect of brassinosteroid(BR) on the physiological and biochemical conditions of 2-year-old Panax notoginseng under the cadmium stress was investigated by the pot experiments. The results showed that cadmium treatment at 10 mg·kg~(-1) inhibited the root viability of P. notoginseng, significantly increased the content of H_2O_2 and MDA in the leaves and roots of P. noto-ginseng, caused oxidative damage of P. notoginseng, and reduced the activities of SOD and CAT. Cadmium stress reduced the chlorophyll content of P. notoginseng, increased leaf F_o, reduced F_m, F_v/F_m, and PIABS, and damaged the photosynthesis system of P. notoginseng. Cadmium treatment increased the soluble sugar content of P. notoginseng leaves and roots, inhibited the synthesis of soluble proteins, reduced the fresh weight and dry weight, and inhibited the growth of P. notoginseng. External spray application of 0.1 mg·L~(-1) BR reduced the H_2O_2 and MDA content in P. notoginseng leaves and roots under the cadmium stress, alleviated cadmium-induced oxidative damage to P. notoginseng, improved the antioxidant enzyme activity and root activity of P. notoginseng, increased the content of chlorophyll, reduced the F_o of P. notoginseng leaves, increased F_m, F_v/F_m, and PIABS, alleviated the cadmium-induced damage to the photosynthesis system, and improved the synthesis ability of soluble proteins. In summary, BR can enhance the anti-cadmium stress ability of P. notoginseng by regulating the antioxidant enzyme system and photosynthesis system of P. notoginseng under the cadmium stress. In the context of 0.1 mg·L~(-1) BR, P. notoginseng can better absorb and utilize light energy and synthesize more nutrients, which is more suitable for the growth and development of P. notoginseng.

Impacts of cadmium on mouse neural stem cells based on dose-response metabomics / 环境与职业医学

Background Cadmium (Cd) is a ubiquitous and toxic heavy metal that can accumulate in human body. Previous studies have shown that Cd exposure can induce neurotoxicity, but the underlying mechanism remains unclear. Objective To investigate the metabolic impacts of multiple doses of Cd on mouse neural stem cells (NSCs), and to explore the potential mechanism and biomarkers of its neurotoxicity. Methods The NSCs were obtained from the subventricular zone (SVZ) of 1-day-old neonatal C57BL/6 mice. The passage 3 (P3) NSCs were exposed to CdCl2 at designed doses (0, 0.5, 1.0, and 1.5 μmol·L−1). The cells were treated with seven replicates, of which one plate was for cell counting. After 24 h of exposure, the intracellular and extracellular metabolites were extracted respectively and then detected by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS). The orthogonal partial least-squares discriminant analysis (OPLS-DA) was applied to visualize the alterations of metabolomic profiles and to identify the differential metabolites (DMs) based on their variable importance for the projection (VIP) value >1 and P<0.05. The metabolite set enrichment analysis (MSEA) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were performed to recognize the significantly altered metabolite sets and pathways. The dose-response relationships were established and the potential biomarkers of Cd exposure were identified by 10% up-regulated or 10% down-regulated effective concentration (EC) of target metabolites. Results A total of 1201 metabolites were identified in the intracellular metabolomic samples and 1207 for the extracellular metabolomic samples. The intracellular and extracellular metabolome of Cd-treated NSCs were distinct from that of the control group, and the difference grew more distant as the Cd dosage increased. At 0.5, 1.0, and 1.5 μmol·L−1 dosage of Cd, 87, 83, and 185 intracellular DMs and 161, 176, and 166 extracellular DMs were identified, respectively. Within the significantly changed metabolites among the four groups, 176 intracellular DMs and 167 extracellular DMs were identified. Both intracellular and extracellular DMs were enriched in multiple lipid metabolite sets. Intracellular DMs were mainly enriched in taurine and hypotaurine metabolism, glycerophospholipid metabolism, and glycerolipid metabolism pathways. Extracellular DMs changed by Cd were mainly enriched in glycerophospholipid metabolism, steroid hormone biosynthesis, and cysteine and methionine metabolism pathways. Among intracellular DMs, 125 metabolites were fitted with dose-response relationships, of which 108 metabolites showed linear changes with the increase of Cd dosage. And 134 metabolites were fitted with dose-response relationships among extracellular DMs, of which 86 metabolites showed linear changes. The intracellular DMs with low EC values were hypotaurine, ethanolamine, phosphatidylethanolamine, and galactose, while the extracellular DMs with low EC values were acetylcholine and 1,5-anhydrosorbitol. Conclusion Cd treatment can significantly alter the intracellular and extracellular metabolome of mouse NSCs in a dose-dependent manner. The neurotoxicity of Cd may be related to glycerophospholipid metabolism. Acetylcholine, ethanolamine, and phosphatidylethanolamine involved in glycerophospholipid metabolism pathway might be potential biomarkers of Cd-induced neurotoxicity.

Microbial remediation of cadmium-contaminated soils and its mechanisms: a review / 生物工程学报

Excessive levels of cadmium (Cd) in soil exert serious negative impacts on soil ecosystems. Microorganisms are a common component of soil and show great potential for mitigating soil Cd. This review summarizes the application and remediation mechanisms of microorganisms, microbial-plants, and microbial-biochar in Cd-contaminated soil. Microorganisms such as Bacillus, Acinetobacter, Pseudomonas, and arbuscular mycorrhizal fungi (AMF) can change the biological validity of Cd through adsorption, mineralization, precipitation and dissolution. Different factors such as pH, temperature, biomass, concentration, and duration have significant effects on Cd bioavailability by microorganisms. Pseudomonas, Burkholderia, and Flavobacterium can promote the uptake of Cd2+ by hyperaccumulator through promotion and activation. Biochar, a soil amendment, possesses unique physicochemical properties and could act as a shelter for microorganisms in agriculture. The use of combined microbial-biochar can further stabilize Cd compared to using biochar alone.

Effect of VIT1/VIT2 overexpression on Fe and Cd accumulation in rice endosperm / 生物工程学报

Iron (Fe) deficiency and excess cadmium (Cd) in rice grain are important problems to be solved in agricultural production. Previous studies have shown that OsVIT1 and OsVIT2 are vacuolar iron transporters. In this study, wild-type ZH11 was selected as the background material and OsVIT1 and OsVIT2 were overexpressed in endosperm by using endosperm specific promoter Glb-1. Field experiments were conducted to study the effect of OsVIT1 and OsVIT2 overexpression on Fe and Cd accumulation in different parts of rice. The results showed that OsVIT1 overexpression in endosperm significantly reduced Fe content in grain by about 50%, while significantly increased zinc (Zn) and copper (Cu) contents in straw and Cu content in grain. OsVIT2 overexpression in endosperm significantly decreased Fe and Cd contents in grain by about 50%, and significantly increased Fe content in straw by 45%-120%. Overexpression of OsVIT1 and OsVIT2 in endosperm did not affect the agronomic traits of rice. In conclusion, OsVIT1 and OsVIT2 overexpression in endosperm reduced Fe accumulation in rice grain, which did not achieve the expected effect. OsVIT2 overexpression in endosperm also decreased Cd accumulation in grain and increased Fe accumulation in straw, which provided reference for iron biofortification and cadmium reduction in rice.