Protective effect of quercetin on lead-induced oxidative stress and endoplasmic reticulum stress in rat liver via the IRE1/JNK and PI3K/Akt pathway

Abstract

Lead (Pb), a well-known environmental toxin, is one of the major hazards for human health. Quercetin (QE), a natural flavonoid, has been reported to have many benefits and medicinal properties. However, its protective effects against Pb-induced endoplasmic reticulum (ER) stress in liver have not been clarified. The aim of the present study was to investigate the effects of quercetin on hepatic ER stress in rats exposed to Pb. Wistar rats were exposed to lead acetate in the drinking water with or without quercetin co-administration for 75 days. Our data showed that quercetin significantly prevented Pb-induced hepatotoxicity in a dose-dependent manner, indicated by both diagnostic indicators of liver damage and histopathological analysis. Quercetin markedly decreased Pb contents in blood and liver. Western blot analysis showed that Pb-induced ER stress in rat liver was significantly inhibited by quercetin. In exploring the underlying mechanisms of quercetin action, we found quercetin markedly suppressed Pb-induced oxidative stress. Quercetin decreased reactive oxygen species (ROS) production and increased the total antioxidant capacity in rat livers. Additionally, quercetin dramatically increased Phosphoinositide-3-kinase (PI3K) and phosphorylated protein kinase B (PKB/Akt) levels in liver rats. In the examined unfolded protein response (UPR) pathways, quercetin markedly inhibited the Pb-induced increase of the phosphorylated inositol-requiring enzyme 1 (IRE1) and c-jun N-terminal kinase (JNK) in rat liver. Taken together, these results suggested that the inhibition of Pb-induced ER stress by quercetin is due at least in part to its anti-oxidant stress activity and its ability to modulate the PI3K/Akt and IRE1/JNK signaling pathway.     

Overcoming the challenge of venous occlusion for lead implantation

Vein stenosis or occlusion is a frequent finding in patients with previously-implanted transvenous leads. This editorial describes the different techniques that may be used to overcome this hurdle in case a new lead needs to be implanted, and discusses two case reports in this issue of the journal.     

Identification of dengue viral RNA-dependent RNA polymerase inhibitor using computational fragment-based approaches and molecular dynamics study

Dengue is a major public health concern in tropical and subtropical countries of the world. There are no specific drugs available to treat dengue. Even though several candidates targeted both viral and host proteins to overcome dengue infection, they have not yet entered into the later stages of clinical trials. In order to design a drug for dengue fever, newly emerged fragment-based drug designing technique was applied. RNA-dependent RNA polymerase, which is essential for dengue viral replication is chosen as a drug target for dengue drug discovery. A cascade of methods, fragment screening, fragment growing, and fragment linking revealed the compound [2-(4-carbamoylpiperidin-1-yl)-2-oxoethyl]8-(1,3-benzothiazol-2-yl)naphthalene-1-carboxylate as a potent dengue viral polymerase inhibitor. Both strain energy and binding free energy calculations predicted that this could be a better inhibitor than the existing ones. Molecular dynamics simulation studies showed that the dengue polymerase–lead complex is stable and their interactions are consistent throughout the simulation. The hydrogen-bonded interactions formed by the residues Arg792, Thr794, Ser796, and Asn405 are the primary contributors for the stability and the rigidity of the polymerase–lead complex. This might keep the polymerase in closed conformation and thus inhibits viral replication. Hence, this might be a promising lead molecule for dengue drug designing. Further optimization of this lead molecule would result in a potent drug for dengue.     

Simultaneous determination of Zn,Cd, Pb,and Cu in urine of patients with blackfoot disease using anodic stripping voltammetry

Blackfoot disease (BFD) is an endemic peripheral vascular disorder resulting in gangrene of the lower extremities, especially the feet, among residents in a limited area on the southwest coast of Taiwan. In the present study, the concentrations of zinc, cadmium, lead, and copper in urine of BFD patients with matched normal controls are investigated by differential pulse anodic stripping voltammetry (DPASV) on a hanging mercury drop electrode (HMDE). The analytical results indicate that urinary copper, cadmium, and lead of the BFD patients are significantly higher than those of the controls. In addition, the patients showed a significantly lower concentration of zinc in the urine than the normal controls. The possible connection of these elements with the etiology of the disease is discussed.     

An integrated assessment of lead exposure in children: Correlation with biochemical and haematological indices

BackgroundLead (Pb) is a worldwide concern due to its persistent property in the environment. However, due to diminutive evidence and elusiveness, the impact of lead exposure on the biochemical and haematological parameter in school-age children is not well established.AimThis study primarily aimed to investigate blood lead (BL) in children and its association with haematological and biochemical parameter.MethodsA total of 43 children (4–12 years) were recruited in each control and study group. Furthermore, the study group were subdivided into two groups (group A (<10 μg/dl) and group B (>10 μg/dl)). BL level, haematological parameter including haemoglobin, packed cell volume, red blood cells, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, total leukocytes count, neutrophils, lymphocytes, monocytes, mean corpuscular volume, red cell distribution width, eosinophil’s, platelets in the whole blood and biochemical parameter such as liver function test (total bilirubin, alkaline phosphatase, serum glutamic-oxaloacetic transaminase, serum glutamic-pyruvic transaminase, total protein, albumin) and kidney function test (sodium, potassium, blood urea nitrogen, creatinine) in serum were measured using anodic stripping voltammeter (ASV), Cell-Dyn Ruby Haematology analyser, Beckman coulter Unicel Dxc 800 Synchron Clinical analyser respectively.ResultsThe arithmetical mean of BL level was 19.93 ± 9.22 μg/dl (median: 17.5 μg/dl; range 9.1–37.4 μg/dl). Only 21 % children had BL levels <10 μg/dl and there were 79 % children with BL levels >10 μg/dl. Blood mean corpuscular haemoglobin concentration, Neutrophils, Monocytes were significantly higher between the control and study group. Additionally, haemoglobin, packed cell volume, red blood cells, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, Lymphocytes and mean corpuscular volume intensities were significantly lower in >10 μg/dl group whereas total leukocytes count, neutrophils, monocytes, red cell distribution width, eosinophil’s, platelets levels were statistically higher (p < 0.001).Serum alkaline phosphatase, serum glutamic-oxaloacetic transaminase, total protein, were higher (p < 0.05) and sodium, albumin were significantly lower in the study group. The mean value of sodium, potassium, total bilirubin, alkaline phosphatase, serum glutamic-pyruvic transaminase, total protein and blood urea nitrogen, creatinine in two groups (<10 μg/dl and >10 μg/dl) was not significantly different. Serum glutamic-oxaloacetic transaminase level was significantly higher (p = 0.015) while albumin levels were significantly lower (p = 0.034) in >10 μg/dl group. A statistically significant correlation of BL levels with all haematological parameters was also observed. Creatinine is positively and albumin was negatively correlated with BL levels.ConclusionThe outcomes specify that high BL levels were significantly associated with higher haematological and biochemical indices in exposed children. However, lead like noxious metals severely affected the haematological, kidney and liver health of children.     

Quantitative Analysis of the Anthropogenic Spatial Transfer of Lead in China

To meet human needs, the geographical location of lead changes during the process of mining lead ore to produce lead products for use by humans. These changes reveal the influence of human activities on lead distribution on the surface of Earth. In this study, a framework was built to analyze changes in lead distribution. Lead was traced through its life cycle using this framework. The provincial administrative unit in mainland of China was defined as the unit of space. The process of anthropogenic spatial transfer of lead was quantitatively analyzed by comparing lead distribution between different areas during each stage of its life cycle in 2010. The results showed that in 2010, around 60% of domestic lead resources were distributed in the Inner Mongolia Autonomous Region, Yunnan Province, and other locations in China. Nearly 80% of the refined lead was produced in Henan, Anhui, Hunan, Yunnan, and Jiangsu provinces. More than 50% of lead products were fabricated and manufactured in Zhejiang, Jiangsu, Shandong, and Hebei provinces. The distribution of lead usage and scrap recovery was relatively uniform (approximately 21 provinces accounted for 1% to 6% of all scrap in the country), although lead products and scrap were mainly distributed in Guangdong, Shandong, Jiangsu, and Zhejiang provinces, which together accounted for nearly 40% of the total. The recycling of lead scrap was mainly concentrated in Anhui (around 57% of the total). Overall, during the whole process, from the mining lead ore from the lithosphere to each stage of the product life cycle, lead was gradually transferred from the south and north of China to the central area and, finally, to the eastern coastal areas.     

Efficiency of Opuntia ficus in the phytoremediation of a soil contaminated with used motor oil and lead,compared to that of Lolium perenne and Aloe barbadensis

Industrial pollutants such as heavy metals and hydrocarbons in soils represent a serious concern due to their persistence and negative effects on the environment, affecting cellular processes in living organisms and even causing mutations and cancer. The main objectives of this work were to evaluate the efficiency of Opuntia ficus in the phytoremediation of a soil polluted with used motor oil. Two other species, one with different and one with similar characteristics, relatively, were used for comparison purposes: Lolium perenne and Aloe barbadensis. The effect of the plants on lead solubility and bioaccumulation, the biomass production of each specie and the microbial counts and bacterial identification for each experiment was studied. Total petroleum hydrocarbons (TPH) were measured every 5 weeks throughout the 20-week phytoremediation experiment. At the end of the experiment soluble Pb, Pb extracted by the plant species, microbiological counts, total biomass and bacterial species in soil were analyzed. Even though Lolium perenne showed the highest TPH removal (47%), Opuntia ficus produced the highest biomass and similar removal (46%). Since Opuntia ficus requires low amounts of water and grows fast, it would be a suitable option in the remediation of soils polluted with hydrocarbons and/or heavy metals.