- The Largest Mass Poisoning in History: Arsenic Contamination of Well Water in Bangladesh. [Journal Article]
- SSkinmed 2018; 16(4):265-267
- Arsenic is a naturally occurring compound that is widely distributed in trace quantities in the environment. Levels toxic to humans have been found contaminating certain regions of the world and thei...
Arsenic is a naturally occurring compound that is widely distributed in trace quantities in the environment. Levels toxic to humans have been found contaminating certain regions of the world and their groundwater, leading to deleterious effects. In fact, an estimated 150 million people are affected by arsenic contamination worldwide.1 Arsenic poisoning leads to several adverse health effects, including cancer of the lung, bladder, and kidney, neurologic disorders, cardiovascular disease, peripheral vascular disease, hypertension, pulmonary disease, and diabetes mellitus.2 Skin lesions are a common manifestation of arsenic poisoning. Early findings include diffuse or spotted melanosis, leukomelanosis, and depigmentation. Years of chronic arsenic poisoning can lead to acral keratoses and squamous cell carcinoma of the skin.3.
- Combination therapy with vitamin C and DMSA for arsenic-fluoride co-exposure in rats. [Journal Article]
- MMetallomics 2018 Aug 24
- CONCLUSIONS: On the basis of the above observations, we suggest that the combinational therapy of DMSA and vitamin C would be more effective in arsenic and/or fluoride toxicity; however, more detailed studies are required to address recoveries in DNA damage.
- Groundwater contamination and the risk of arsenic poisoning in Pakistan. [Journal Article]
- JPJ Pak Med Assoc 2018; 68(8):1288
- N-Terminal Extension and C-Terminal Domains Are Required for ABCB6/HMT-1 Protein Interactions, Function in Cadmium Detoxification, and Localization to the Endosomal-Recycling System in Caenorhabditis elegans. [Journal Article]
- FPFront Physiol 2018; 9:885
- The chronic exposure of humans to toxic metals such as cadmium from food and air causes dysfunction of vital organs, neurodegenerative conditions, and cancer. In this regard, members of the ABCB sub-...
The chronic exposure of humans to toxic metals such as cadmium from food and air causes dysfunction of vital organs, neurodegenerative conditions, and cancer. In this regard, members of the ABCB sub-family of the ATP-binding cassette (ABC) transporter superfamily, ABCB6/HMT-1, are acutely required for the detoxification of heavy metals and are present in genomes of many organisms including the nematode worm, Caenorhabditis elegans and humans. We showed previously that C. elegans ABCB6/HMT-1 detoxifies cadmium, copper, and arsenic, and is expressed in liver-like cells, the coelomocytes, head neurons and intestinal cells, which are the cell types that are affected by heavy metal poisoning in humans. The subcellular localization of ABCB6/HMT-1 proteins is unclear. ABCB6/HMT-1 proteins have a distinguishing topology: in addition to one transmembrane domain and one nucleotide-binding domain, they possess a hydrophobic N-terminal extension (NTE) domain encompassing five to six transmembrane spans. The role of the NTE domain in the function of ABCB6/HMT-1 in the native organism remains to be investigated. We used a versatile, multicellular model system, C. elegans, to establish the subcellular localization of ABCB6/HMT-1 and refine its structure-function studies in the native organism. We show that ABCB6/HMT-1 localizes mainly to the apical recycling endosomes and, in part, to early and late endosomes of intestinal cells. We also show that ABCB6/HMT-1 lacking the NTE domain is mistargeted to the plasma membrane and is unable to confer cadmium resistance. Although the NTE domain is essential for ABCB6/HMT-1 interaction with itself, the absence of NTE does not fully prevent this interaction. As a result, ABCB6/HMT-1 lacking the NTE domain, and expressed in wild-type worms or co-expressed with the full-length polypeptide, inactivates and mistargets the full-length ABCB6/HMT-1. We also show that the 43 amino acid residue stretch at the COOH-terminus is required for the ABCB6/HMT-1 interaction with itself and cadmium detoxification function. These results suggest that both NTE and COOH-terminus must be present to allow the protein to interact with itself and confer cadmium resistance. Considering that ABCB6/HMT-1 proteins are highly conserved, this study advances our understanding of how these proteins function in cadmium resistance in different species. Furthermore, these studies uncover the role of the endosomal-recycling system in cadmium detoxification.
- Arsenic trioxide exposure accelerates colon preneoplasic aberrant crypt foci induction regionally through mitochondrial dysfunction. [Journal Article]
- TRToxicol Res (Camb) 2018 Mar 01; 7(2):182-190
- Arsenic poisoning is a worldwide problem. Thus, we studied the effects of arsenic trioxide (ATO) administration on a 1,2-dimethylhydrazine (DMH)-induced preneoplasic colon carcinogenesis model. Mice ...
Arsenic poisoning is a worldwide problem. Thus, we studied the effects of arsenic trioxide (ATO) administration on a 1,2-dimethylhydrazine (DMH)-induced preneoplasic colon carcinogenesis model. Mice were separated into four study groups; the control group received only vehicles. The ATO group received daily a 2.5 mg kg-1 dose for 4 weeks. The DMH group received DMH (20 mg kg-1) twice in two weeks. The third group (D-ATO) had the same as the DMH group with ATO administration starting at week 10. At the end of 14 weeks, colons from sacrificed mice were taken, segmented into distal and proximal and subjected to aberrant crypt foci (ACF), aberrant crypt (AC) counting, alcian blue, H&E and Hoechst histological study and lastly oxidative stress marker analysis as well as mitochondrial swelling assessment. Data showed a significant increase in ACF and AC after DMH treatment, which was further increased after ATO addition. A perturbed histological structure was observed and loss of mucin producing cells in the colon tissue was observed. An important impact on the distal colon compared to the proximal one was noticed. The oxidative stress balance showed a similar pattern with an increase in MPO, NO/l-ornithine balance and MDA, while a decrease was observed in the antioxidant enzymes (CAT, SOD and GSH). In all parameters analyzed, the distal colons showed higher values than proximal. Furthermore, histological cell death analysis in combination with mitochondrial permeability pore opening suggested ATO contribution in the pathological effect. Our study has shown that ATO administration accelerated colon cancer development suggesting the heaviness of such treatments and the need to explore combinations and cycle type formulas.
- HER2 and Src co-regulate proliferation, migration and transformation by downstream signaling pathways in arsenite-treated human uroepithelial cells. [Journal Article]
- MMetallomics 2018 Aug 15; 10(8):1141-1159
- Epidemiological studies have established a strong association between arsenic exposure in drinking water and an increased incidence of bladder cancer in arseniasis-endemic areas. Increased expression...
Epidemiological studies have established a strong association between arsenic exposure in drinking water and an increased incidence of bladder cancer in arseniasis-endemic areas. Increased expression of HER2 has been observed in various types of human malignancies including bladder cancer. This study investigated the role of HER2 in arsenite-induced transformation of uroepithelial cells SV-HUC-1 and the role of Src family kinases in HER2 signaling. We found that the expression HER2 and Src were increased following chronic arsenite exposure in a time-dependent fashion. Chronic arsenite exposure also led to an upregulation of proliferation factors such as cyclin D1, COX2, PCNA, VEGF, and HIF-1α. Furthermore, Ras/Raf/MAPK, PI3K/AKT, and JAK2/STAT3 signaling pathways were activated by arsenite treatment. Importantly, these changes were inhibited by HER2 inhibitors and in HER2 knocked down cells. In addition, downregulation of HER2 inhibited cell growth and migration properties of arsenite-treated cells. Inhibition of Src also inhibits activation of signaling pathways and malignant transformation of cells. And we obtained evidence of an interaction between HER2 and Src in SV-HUC-1 cell lines. These results suggest that HER2 and Src may play an important role in arsenite-induced transformation by multiple downstream signals pathways.
- Metal Biomonitoring and Comparative Assessment in Urine of Workers in Lead-Zinc and Steel-Iron Mining and Smelting. [Journal Article]
- BTBiol Trace Elem Res 2018 Jul 27
- The exposure of heavy metals (lead (Pb), cadmium (Cd), copper (Cu), nickel (Ni), and metalloid arsenicals) and their effects on workers' health from a lead-zinc mine (145 workers) and a steel smeltin...
The exposure of heavy metals (lead (Pb), cadmium (Cd), copper (Cu), nickel (Ni), and metalloid arsenicals) and their effects on workers' health from a lead-zinc mine (145 workers) and a steel smelting plant (162 workers) was investigated. Information on subject characteristics was obtained through a questionnaire. We determined the urinary levels of Pb, Cd, Cu, Ni, and arsenicals (including inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA), as were 8-hydroxydeoxyguanosine (8-OHdG) and cystatin C. Lead-zinc mine foundry workers had significantly higher concentrations of urinary Pb, Cd, Cu, Ni, iAs, and MMA than did steel smelting plant workers. Individuals who had consumed seafood in the previous 3 days had higher concentrations of urinary Ni than did individuals who had not consumed seafood. The urinary Cd concentrations in the two groups of factory workers may have been affected by daily smoking. There was no significant difference in urinary 8-OHdG between workers from the lead-zinc mine foundry and the steel smelting plant. Urinary Pb and Cd had significant positive linear dose-dependent effects on 8-OHdG. Urinary cystatin C, a sensitive biological indicator reflecting early renal damage, was found at higher levels in lead-zinc mine workers than in steel smelting plant workers. Binary logistic regression analysis showed that age and urinary Cd were significantly associated with urinary cystatin C. These results indicated that workers from lead-zinc mines may be exposed to higher levels of heavy metals which could lead to greater risk of kidney damage.
- The PKCδ-Nrf2-ARE signalling pathway may be involved in oxidative stress in arsenic-induced liver damage in rats. [Journal Article]
- ETEnviron Toxicol Pharmacol 2018; 62:79-87
- Arsenic poisoning is a worldwide endemic disease that affects thousands of people. Growing evidence from animal, cell, and human studies indicates that arsenic has deleterious effects on the liver. O...
Arsenic poisoning is a worldwide endemic disease that affects thousands of people. Growing evidence from animal, cell, and human studies indicates that arsenic has deleterious effects on the liver. Oxidative stress is considered the primary mechanism for arsenic toxicity in liver damage. However, the mechanisms remain unclear. In light of this fact, the main objective of this study was to investigate the effects of the protein kinase C delta-nuclear factor E2-related factor 2-antioxidant response element (PKCδ-Nrf2-ARE) signalling pathway on oxidative stress in liver damage. In the present study, we used a model of liver damage induced by coal-burning arsenic in rats, which was set up by our research group. The oxidative stress index and the transcription and protein expression levels of PKCδ, Nrf2, Keap1, SOD1, and GPx1 were detected, and then their correlation analyses were carried out. The results demonstrated that coal-burning arsenic can cause oxidative stress liver damage in rats, which may be related to the PKCδ-Nrf2-ARE signalling pathway. This study may provide a new pathway for studies of the mechanisms of arsenism.
- A Sickening Tale. [Case Reports]
- NEJMN Engl J Med 2018 07 05; 379(1):75-80
New Search Next
- ABCA1 Is Coordinated with ABCB1 in the Arsenic-Resistance of Human Cells. [Journal Article]
- ABAppl Biochem Biotechnol 2018 Jun 28
- Arsenic is one of the most widespread global environmental toxicants associated with endemic poisoning. ATP-binding cassette (ABC) proteins are transmembrane channels that transport and dispose of li...
Arsenic is one of the most widespread global environmental toxicants associated with endemic poisoning. ATP-binding cassette (ABC) proteins are transmembrane channels that transport and dispose of lipids and metabolic products across the plasma membrane. The majority of ABC family members (including ABCB1 and ABCC1) are reported to play a role in the development of arsenic and drug resistance in mammals. Previously, we established a human arsenic-resistant ECV-304 (AsRE) cell line and identified ABCA1 as a novel arsenic resistance gene. In the current study, we further investigated the potential contribution of ABCA1, ABCB1, and ABCC1 to arsenic resistance through measurement of survival rates and arsenic accumulation in AsRE cells with RNA interference. The arsenic resistance capacity of ABCC1 was the strongest among the three genes, while those of ABCA1 and ABCB1 were similar. Double or triple gene knockdown of ABCA1, ABCB1, and ABCC1 via RNA interference led to a decrease significant in arsenic resistance when ABCA1/ABCB1 or ABCB1/ABCC1 were simultaneously silenced. Interestingly, no differences were evident between cells with ABCA1/ABCC1 and ABCC1 only knockdown. Our findings suggest that ABCA1 and ABCB1 proteins display similar arsenic resistance capabilities and possibly coordinate to promote arsenic resistance in AsRE cells.