Flavonoids and stilbenoids as a promising arsenal for the management of chronic arsenic toxicity

Rapid industrial and technological development has impacted ecosystem homeostasis strongly. Arsenic is one of the most detrimental environmental toxins and its management with chelating agents remains a matter of concern due to associated adverse effects. Thus, safer and more effective alternative therapy is required to manage arsenic toxicity. Based on existing evidence, native and indigenous plant-based active biomolecules appear as a promising strategy to mitigate arsenic-induced toxicity with an acceptable safety profile. In this regard, various phytochemicals (flavonoids and stilbenoids) are considered important classes of polyphenolic compounds with antioxidant and chelation effects, which may facilitate the removal of arsenic from the body more effectively and safely with regard to conventional approaches. This review presents an overview of conventional chelating agents and the potential role of flavonoids and stilbenoids in ameliorating arsenic toxicity. This report may provide a roadmap for identifying novel prophylactic/therapeutic strategies for managing arsenic toxicity.     

Assessment of heavy metals by ICP-OES and their impact on insulin stimulating hormone and carbohydrate metabolizing enzymes

Arsenic (As) and cadmium (Cd) have recently emerged as major health concerns owing to their strong association with diabetes mellitus (DM). We aimed to investigate the heavy metals exposure towards incidence of DM at various enzymatic and hormonal levels. Additionally, association of As and Cd with Zinc (Zn, essential metal) was also evaluated. Spot urine samples were collected to assess As, Cd and Zn through ICP-OES. Serum was analyzed by assay method for fasting blood glucose, liver and renal function biomarkers. ELISA was performed to investigate the impact of heavy metals on HbA1c, α-amylase, DPP-IV, IGF-1, leptin, GSH, MDA, SOD, HDL, FFA, TG and interleukin (IL)-6. Association of heavy metals with DM was measured by odds ratio (OR) and level of significance was assessed by Chi-squared test. Unpaired student's t-test was used to compare DM-associated risk factors in heavy metals-exposed and unexposed participants. As and Cd were detectable in 75.4% and 83% participants with mean concentration of 75.5 ppb and 54.5 ppb, respectively. For As exposure, OR in the third quartile was maximum ie 1.34 (95% CI, 0.80 to 2.23), however the result was not statistically significant (P > .05). For Cd exposure, OR in the fourth quartile was considerably high, 1.62 (95% CI, 1.00 to 2.61), with a significant probability value (P < .05). Urinary Cd was negatively associated with Zn. As and Cd exposure increases the incidence of DM in the general population. Impaired hormonal and enzymatic levels in diabetic and non-diabetic exposed participants reflect the multiple organ damage by heavy metal exposure.     

空间统计学在食品污染物分布研究中的应用

目的 以2017年某省食品安全监测大米中砷含量数据为例，探讨空间统计学方法在食品污染物分析中的应用价值。方法 采用空间点模式估计、核密度分析，全局以及局部自相关性分析等空间统计学方法，在县级空间尺度下，对某省大米中砷含量进行探索性空间数据分析。结果 空间点模式分布图显示，该省大米砷污染的空间分布比较分散，核密度分析结果显示污染热点区域主要在该省中东部地区。全局自相关Moran''s I指数值为0.11，有统计学意义，大米样品中砷污染呈现出低度空间聚集性。有1个"高-高"聚集区，2个典型的"低-低"聚集区。结论 空间统计学运用于食物污染物分布研究上，可以很好地可视化展示、识别污染分布规律、热点地区和聚集区，为基于问题的监测工作的开展提供技术支持。     

三氧化二砷联合全反式维甲酸治疗急性早幼粒细胞白血病的初步观察

目的　观察三氧化二砷 (As2 O3 )联合全反式维甲酸 (ATRA)治疗急性早幼粒细胞白血病(APL)的疗效和不良反应。方法　As2 O3 联合ATRA治疗初治和复发APL患者 2 0例 (可评价的患者 18例 )。治疗方法如下 :As2 O3 (0 .1%溶液 ) 10ml加入 5 0g L葡萄糖溶液 5 0 0ml静脉点滴 ,持续 4～ 6h ,1次 d ;ATRA 2 5mg·m- 2 ·d- 1 ,分 2～ 3次服用。结果　 17例患者获得完全缓解 (CR) ,CR率 94.4%。 14例初治患者均获得CR ,4例复发患者中 3例取得CR。均在 30d内达CR。没有发现明显的不良反应。结论　ATRA联合As2 O3 治疗APL患者不仅能获得好的疗效 ,而且能缩短达CR的时间。     

三氧化二砷对U2-OS人骨肉瘤细胞形态及细胞凋亡的影响

目的研究三氧化二砷在体外对人骨肉瘤细胞(U2-OS)形态及细胞凋亡的影响。方法以不同浓度三氧化二砷(0.5、1.0、1.5μmol/L)作用骨肉瘤细胞,15 mg/L 5-FU作为阳性对照,采用荧光显微镜观察细胞核形态及流式细胞仪检测细胞凋亡率。结果各浓度的三氧化二砷对骨肉瘤细胞(U2-OS)的形态均有影响,随着三氧化二砷浓度的升高,细胞核发生固缩越明显,细胞凋亡率越高,与正常对照组相比,差异具统计学意义。结论三氧化二砷可导致骨肉瘤细胞(U2-OS)细胞核发生固缩坏死和凋亡,凋亡率与三氧化二砷浓度有依赖关系,在一定浓度范围内随浓度增高而增高。     

三氧化二砷诱导胰腺癌细胞系PC-3凋亡及其抑制转移的作用

目的:探讨三氧化二砷(亚砷酸,As2O3)注射液诱导人类胰腺癌细胞凋亡及其抑制转移的作用机制.方法:用AS2O3处理人胰腺癌细胞株PC-3,通过流式细胞仪观察细胞的凋亡率及生长周期的变化;用免疫组织化学的方法,检测凋亡相关基因蛋白Fas,Fas-L,Bc1-2和Bax及转移相关基因蛋白CD44和nm23表达的变化.结果:流式细胞仪检测显示明显的凋亡峰出现,并使细胞周期主要被阻滞在S期(14.9%-63.7%);免疫组化结果显示,Bc1-2( ～ ),CD44( ～ )基因的表达下调,Fas( ～ )、Fas-L(-～ )及nm23( ～ )基因的表达上调.结论:As2O3注射液可诱导人类胰腺癌细胞株PC-3凋亡并具有抑制转移作用,这可能与调节Bc1-2,Fas,Fas-L及CD44,nm23蛋白的表达有关.     

Anti-hepatoma effect of arsenic trioxide on experimental liver cancer induced by 2-acetamidofiuorene in rats

AIM: To study the anti-hepatoma efficiency of arsenic trioxide (As2O3) in the treatment of experimental rat hepatocellular carcinoma (HCC) induced by 2-acetamidofluorene (2-FAA)and to elucidate the possible mechanisms.METHODS: SD rats (2 mo old) had been fed with 2-FAA for 8 wk to induce HCC, and then they were treated with As2O3 or matrine. On d 29, the rats were killed and the liver was weighed and liver tumors were counted. The histological changes of liver tissue were observed under microscope, and the cellular dynamic parameters were studied by flow cytometry. Immunohistochemistry (two-step method) was used to observe the expression of vascular endothelial growth factor (VEGF) and micro-vessel density (MVD) on consecutive sections. The pathological parameters were also analyzed, the levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT),total bilirubin (TBi), and direct bilirubin (DBi).RESULTS: The number of liver tumors decreasedsignificantly in groups treated with As2O3, especially in medium-dose (1 mg/kg) group (t = 2.80, P＜0.01). As2O3 caused HCC cell death via apoptosis; necrosis was seen and apoptosis was common when the dose was 1 mg/kg.Proliferation index decreased sharply in medium-dose (1 mg/kg) group (7.87±4.11 vs 24.46±6.49, t = 2087,P＜0.01), but not in 0.2 mg/kg group. However, S-phase fraction decreased dramatically in both groups, it reached the bottom level only when the dose was 1 mg/kg compared with control (0.40±0.13 vs 3.01±0.51, t = 2.97, P＜0.01),and it was obviously accompanied with accumulation of cells in G0/G± (G0/G1 restriction). The expressions of VEGF and MVD in medium-dose (1 mg/kg) group were significantly lower than normal saline group (0.63±0.74 vs 2.44±0.88, P＜0.05; 15.75±3.99 vs47.44±13.41, t= 2.80,P＜0.01). Compared with normal saline group, mediumand low-dose groups As2O3 and matrine lowered the levels of ALT in serum (61.46±9.46, 63.75±20.40, 61.18±13.00 vs 108.98±29.86, t= 2.14, P＜0.05), but had no effect on the level of serum AST, TBi, and DBi.CONCLUSION: As2O3 had inhibitory effect on growth of experimental HCC in rats induced by 2-FAA, but had no obvious effect on normal hepatic cells. The mechanisms may involve decrease of cell division, accumulation of cells in G0/G1 phase, apoptosis of tumor cells, and inhibitory effect on angiogenesis through blocking VEGF.