Low-Dose Colchicine Ameliorates Doxorubicin Cardiotoxicity Via Promoting Autolysosome Degradation.

BACKGROUND: The only clinically approved drug that reduces doxorubicin cardiotoxicity is dexrazoxane, but its application is limited due to the risk of secondary malignancies. So, exploring alternative effective molecules to attenuate its cardiotoxicity is crucial. Colchicine is a safe and well-tolerated drug that helps reduce the production of reactive oxygen species. High doses of colchicine have been reported to block the fusion of autophagosomes and lysosomes in cancer cells. However, the impact of colchicine on the autophagy activity within cardiomyocytes remains inadequately elucidated. Recent studies have highlighted the beneficial effects of colchicine on patients with pericarditis, postprocedural atrial fibrillation, and coronary artery disease. It remains ambiguous how colchicine regulates autophagic flux in doxorubicin-induced heart failure. METHODS AND RESULTS: Doxorubicin was administered to establish models of heart failure both in vivo and in vitro. Prior studies have reported that doxorubicin impeded the breakdown of autophagic vacuoles, resulting in damaged mitochondria and the accumulation of reactive oxygen species. Following the administration of a low dose of colchicine (0.1 mg/kg, daily), significant improvements were observed in heart function (left ventricular ejection fraction: doxorubicin group versus treatment group=43.75%±3.614% versus 57.07%±2.968%, P=0.0373). In terms of mechanism, a low dose of colchicine facilitated the degradation of autolysosomes, thereby mitigating doxorubicin-induced cardiotoxicity. CONCLUSIONS: Our research has shown that a low dose of colchicine is pivotal in restoring the autophagy activity, thereby attenuating the cardiotoxicity induced by doxorubicin. Consequently, colchicine emerges as a promising therapeutic candidate to improve doxorubicin cardiotoxicity.

Heavy Metal in Rice and Vegetable and Human Exposure near a Large Pb/Zn Smelter in Central China.

Non-ferrous metal smelting is a significant source of anthropogenic heavy metal emission and has led to severe environmental pollution that ultimately threatens the health of local residents. In this study, we determined concentrations of copper (Cu), zinc (Zn), cadmium (Cd) and lead (Pb), as well as Pb isotopic compositions in rice, vegetables and human hair in areas surrounding the Zhuzhou Pb/Zn smelter in Hunan, China and we assessed the health risks associated with rice and vegetable consumption for local residents. Results showed that rice and vegetable samples were significantly contaminated by Cd and Pb. Age and source of rice were important factors for the enrichment of heavy metal concentrations in human hair. The ratios of Pb isotopes in human hair (1.164-1.170 for 206Pb/207Pb and 2.102-2.110 for208Pb/206Pb) were comparable to those in rice (1.162-1.172 for 206Pb/207Pb and 2.098-2.114 for208Pb/206Pb) and were slightly lower than those in vegetables (1.168-1.172 for 206Pb/207Pb and 2.109-2.111 for208Pb/206Pb), indicating that Pb in human hair mainly originated from food ingestion. A non-carcinogenic risk assessment showed that Cd exposure was the dominant health risk for local residents. This study suggested that crops planted surrounding the smelter were seriously contaminated with Cd and human exposure was related to dietary intake.

Fate of Lead and Cadmium in Precalciner Cement Plants and Their Atmospheric Releases.

Disclosing the fate of lead (Pb) and cadmium (Cd) during the cement production process is the key to control their atmospheric emissions, which have not attracted much attention yet. In this study, three precalciner cement plants (CPs) using different raw materials in Guizhou Province in Southwest China were investigated. It showed that the concentrations of Pb and Cd in different raw materials and the associated total metal input of these materials were different among CPs; the behavior of Pb and Cd were almost the same during the clinker production process that there has been no accumulation of these two elements inside the system, and nearly all input of Pb and Cd were discharged by the clinker. Although the temperature of clinkerization was pretty high of 1450 °C, the atmospheric emission ratio of both metals was negligible (<0.006% for Pb and <0.002% for Cd of the total output, respectively); the main reason might be that the two elements were incorporated into the minerals of clinker, either as silicate or sulfate. The long-term environmental impacts of some high Pb-and Cd-laden clinkers and cement need to be monitored and evaluated.

Heavy Metal(loid)s Contamination in Ground Dust and Associated Health Risks at a Former Indigenous Zinc Smelting Area.

Indigenous zinc smelting (IZS) is a backward technique that releases a great deal of heavy metal(loid)s into the environment. However, the contamination of heavy metal(loid)s in ground dust and the associated health risks in such areas are poorly known. In this study, a former IZS area in Guizhou, China, was surveyed during 2008-2018 with 15 elements (Ag, As, Bi, Cd, Co, Cr, Cu, Hg, In, Ni, Pb, Sb, Sn, Tl, Zn) being analyzed. The results indicate that most elements (e.g., Ag, As, Cd, Cu, Pb, Sb, Sn, Zn) in ground dust decreased significantly after the cessation of the IZS in 2006; nevertheless, some elements still remained at relatively high levels in 2018, e.g., Pb (average: 762 ± 647 mg/kg), Zn (average: 1287 ± 753 mg/kg), Cd (average: 7.76 ± 5.06 mg/kg), and As (average: 41.9 ± 34.8 mg/kg), indicating they might come from the local contaminated soils, slag residues and smelting potteries. In terms of the impacts on human health, children have both higher non-carcinogenic and carcinogenic risks than that of adults, with the latter subpopulation having a lower risk than the threshold values. Pb and As were the two elements with the highest non-carcinogenic risk for children, the hazard index of local children was still higher than the threshold of 1 (e.g., 1.43 for As, 2.09 for Pb) in 2018. The carcinogenic risk of As exposure to children dropped more than two times to 6.42 × 10-7 in 2018, which falls below the tolerable range (10-6-10-4). This study revealed that although the concentration of heavy metal(loid)s in ground dust and linked health risk in the IZS area has reduced dramatically after the cessation of IZS, continued removal of slag residues and smelting potteries is necessary for further decreasing the human health risk.

Source apportionment of heavy metal and their health risks in soil-dustfall-plant system nearby a typical non-ferrous metal mining area of Tongling, Eastern China.

The agricultural land-atmospheric dustfall-plant system around the mining area is at high risks of heavy metal pollution caused by mining-smelting activities. In this study, 118 samples (including rhizospheric soils, background soils, soil-forming parent rocks, crops, vegetables, medicinal plants and atmospheric dustfall) were collected nearby Tongling Cu-Fe-Au mining area, Eastern China. We studied the concentrations, migration, sources, and health risks through consumption of two main crops (corn and rice), six kinds of vegetables, and medicinal plants (Fengdan, Paeonia ostii) for six metal elements (Cu, Zn, Cr, Cd, Pb and Hg). Results revealed Cr and Cd in soils, and Cd, Cr, Pb, Cu and Zn in dustfall showed a relatively high contamination degree. The mean contents of Cr and Pb in corn kernels, as well as Cd, Cr and Pb in rice grains and all vegetables, and Cr in Fengdan cortex moutan exceeded the corresponding food safety limits in China. The transfer capability of Cr in corn kernels and rice grains, Pb in edible vegetables, and Cd in cortex moutan were the strongest, respectively. Health risk assessment results showed Cr had the greatest non-carcinogenic risk, followed by Pb and Cd. The results of pearson's correlation analysis (CA), hierarchical cluster analysis (HCA), and principal component analysis (PCA) indicated Zn-Cr, Pb and Cd-Cu-Hg in the plants might derive from different geochemical end-members. Source apportionment based on lead isotope showed that mining-smelting activities were the major source of Pb in atmospheric dustfall and agricultural soils, with the average contribution rates of 66% and 50%, respectively. Vehicle emissions from diesel fuels (50%-68%) and mining-smelting activities (16%-25%) contributed mainly to Pb accumulation in plants. Hence, our study suggested the accumulations of Pb in plants might be mainly from the direct foliar uptake of atmospheric Pb related to vehicle emissions and mining-smelting activities.

Contaminations, Sources, and Health Risks of Trace Metal(loid)s in Street Dust of a Small City Impacted by Artisanal Zn Smelting Activities.

To investigate the impact of artisanal zinc smelting activities (AZSA) on the distribution and enrichment of trace metal(loid)s in street dust of a small city in Guizhou province, SW China, street dust samples were collected and analyzed for 10 trace metal(loid)s (Cr, Co, Ni, Cu, Zn, As, Cd, Sb, Pb, and Hg). Meanwhile, the health risks of local resident exposed to street dust were assessed. The result showed that the average concentrations of 10 elements were Zn (1039 mg kg-1), Pb (423 mg kg-1), Cr (119 mg kg-1), Cu (99 mg kg-1), As (55 mg kg-1), Ni (39 mg kg-1), Co (18 mg kg-1), Sb (7.6 mg kg-1), Cd (2.6 mg kg-1), and Hg (0.22 mg kg-1). Except Ni, Co, and Cr, other elements in street dust were obviously elevated compared to the provincial soil background. Pb, Zn, Cd, Sb, and Cu were at heavy to moderate contamination status, especially Pb and Zn, with maximums of 1723 and 708 mg kg-1, respectively; As and Hg were slightly contaminated; while Cr, Ni, and Co were at un-contaminated levels. Multivariate statistical analysis revealed AZSA contributed to the increase of Pb, Zn, Cd, Sb, As, and Hg, while, natural sources introduced Ni, Co, Cr, and Cu. The health risk assessment disclosed that children had higher non-carcinogenic risk than those found in adults, and As has hazardous index (HI) higher than 1 both for children and adults, while Pb and Cr only had HIs higher than 1 for children, other elements were relatively safe. For carcinogenic risks, the major concern was As, then a lesser concern for Cr. The study showed that although the scale of AZSA was small, the contamination of heavy metal(loid)s in street dust and associated health risks were severe.

Rare earth elements in street dust and associated health risk in a municipal industrial base of central China.

The content levels, distribution characteristics, and health risks associated with 15 rare earth elements (REEs) in urban street dust from an industrial city, Zhuzhou, in central China were investigated. The total REE content (∑REE) ranged from 66.1 to 237.4 mg kg-1, with an average of 115.9 mg kg-1, which is lower than that of Chinese background soil and Yangtze river sediment. Average content of the individual REE in street dust decreased in the order Ce > La > Nd > Y > Pr > Sm > Gd > Dy > Er > Yb > Eu > Ho > Tb > Tm > Lu. The chondrite-normalized REE pattern indicated light REE (LREE) enrichment, a relatively steep LREE trend, heavy REE (HREE) depletion, a flat HREE trend, a Eu-negative anomaly and a Ce-positive anomaly. Foremost heavy local soil and to less degree anthropogenic pollution are the main sources of REE present in street dust. Health risk associated with the exposure of REE in street dust was assessed based on the carcinogenic and non-carcinogenic effect and lifetime average daily dose. The obtained cancer and non-cancer risk values prompt for no augmented health hazard. However, children had greater health risks than that of adults.

Metal Exposure and Associated Health Risk to Human Beings by Street Dust in a Heavily Industrialized City of Hunan Province, Central China.

Fifty-five urban street dust samples were collected from Zhuzhou, an industrial city in central China and analyzed for a range of toxic elements. Potential carcinogenic and non-carcinogenic health effects on children and adults due to exposure to street dust were assessed. Concerning the two subgroups, the child cohort is confronted with considerably greater health risks than adults. According to the Hazard Quotient (HQ) method, ingestion of dust particles poses primary risk to children and adults, followed by dermal contact and inhalation for all of the metals investigated except Hg, for which inhalation of its elemental vapor constitute a slightly higher risk than ingestion. For children, Pb, As, Cd, Cr, Hg and Sb exposure were deemed as the highest contributors to non-cancer health risks, while As and Cr represent an enhanced cancer risk for children. For adults, risk indicator values for both cancer and non-cancer effects obtained were within the safety threshold. In a comparison with other locations within and outside mainland China, exposure to arsenic is prominent for the population of Zhuzhou, indicating more attention and preventive actions should been taken.

Mercury exposures and symptoms in smelting workers of artisanal mercury mines in Wuchuan, Guizhou, China.

Mercury exposures to smelting workers of artisanal mercury mines in Wuchuan, Guizhou, China were evaluated by urine and hair mercury survey. The mean urinary mercury (U-Hg), hair total mercury (T-Hg), and hair methyl mercury (Me-Hg) for smelting workers was 1060 microg/g creatinine (microg/g Cr), 69.3 and 2.32 microg/g, respectively. The results were significantly higher than that of control group, which is 1.30 microg/g Cr, 0.78 and 0.65 microg/g, correspondingly. The average urinary beta2-microglobulin (beta2-MG) was 248 microg/g Cr for the exposed group contrasting to 73.5 microg/g Cr for the control group and the data showed a serious adverse effect on renal system for the smelting workers. The workers were exposed to mercury vapor through inhalation, and the exposure route of Me-Hg may be through intake of polluted diet. The results indicate that age, alcohol drinking, and smoking are not crucial factors controlling the urine and hair mercury levels for the exposed and the control group. Clinical symptoms including finger and eyelid tremor, gingivitis, and typical dark-line on gums were observed in six workers. This study indicated that the smelting workers in Wuchuan were seriously exposed to mercury vapor.