scholarly journals Coenzyme Q10 protected against arsenite and enhanced the capacity of 2,3-dimercaptosuccinic acid to ameliorate arsenite-induced toxicity in mice

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Victoria K. Mwaeni ◽  
James N. Nyariki ◽  
Ngalla Jillani ◽  
George Omwenga ◽  
Mathew Ngugi ◽  
...  
Keyword(s):  
Histological Analysis ◽  
Cell Damage ◽  
Coenzyme Q ◽  
Inorganic Arsenic ◽  
Organ Damage ◽  
Pharmacological Intervention ◽  
Oral Exposure ◽  
Arsenic Poisoning ◽  
Liver And Kidney ◽  
Organic Arsenic

Abstract Background Arsenic poisoning affects millions of people. The inorganic forms of arsenic are more toxic. Treatment for arsenic poisoning relies on chelation of extracellularly circulating arsenic molecules by 2,3-dimecaptosuccinic acid (DMSA). As a pharmacological intervention, DMSA is unable to chelate arsenic molecules from intracellular spaces. The consequence is continued toxicity and cell damage in the presence of DMSA. A two-pronged approach that removes extracellular arsenic, while protecting from the intracellular arsenic would provide a better pharmacotherapeutic outcome. In this study, Coenzyme Q10 (CoQ10), which has been shown to protect from intracellular organic arsenic, was administered separately or with DMSA; following oral exposure to sodium meta-arsenite (NaAsO2) – a very toxic trivalent form of inorganic arsenic. The aim was to determine if CoQ10 alone or when co-administered with DMSA would nullify arsenite-induced toxicity in mice. Methods Group one represented the control; the second group was treated with NaAsO2 (15 mg/kg) daily for 30 days, the third, fourth and fifth groups of mice were given NaAsO2 and treated with 200 mg/kg CoQ10 (30 days) and 50 mg/kg DMSA (5 days) either alone or in combination. Results Administration of CoQ10 and DMSA resulted in protection from arsenic-induced suppression of RBCs, haematocrit and hemoglobin levels. CoQ10 and DMSA protected from arsenic-induced alteration of WBCs, basophils, neutrophils, monocytes, eosinophils and platelets. Arsenite-induced dyslipidemia was nullified by administration of CoQ10 alone or in combination with DMSA. Arsenite induced a drastic depletion of the liver and brain GSH; that was significantly blocked by CoQ10 and DMSA alone or in combination. Exposure to arsenite resulted in significant elevation of liver and kidney damage markers. The histological analysis of respective organs confirmed arsenic-induced organ damage, which was ameliorated by CoQ10 alone or when co-administered with DMSA. When administered alone, DMSA did not prevent arsenic-driven tissue damage. Conclusions Findings from this study demonstrate that CoQ10 and DMSA separately or in a combination, significantly protect against arsenic-driven toxicity in mice. It is evident that with further pre-clinical and clinical studies, an adjunct therapy that incorporates CoQ10 alongside DMSA may find applications in nullifying arsenic-driven toxicity.

MICROSCOPIC CHANGES IN THE INTERNAL ORGANS OF WHITE MICE DURING EXPERIMENTAL IRON (IV) CLATHROCHELATE TOXICOSIS

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
B. V. Borysevych ◽  
◽  
V. V. Lisova ◽  
I. M. Derkach ◽  
S. S. Derkach ◽  
...  
Keyword(s):  
Biological Response ◽  
Organ Damage ◽  
The Body ◽  
New Drugs ◽  
Laboratory Animals ◽  
Internal Organs ◽  
Experimental Drug ◽  
Liver And Kidney ◽  
Preclinical And Clinical Studies ◽  
First Time

Iron (IV) clathrochelate based on a macrobicyclic ligand of the hexahydrazide type is a unique compound that contains iron in a rare high valence IV. Preclinical and clinical studies of this complex, which were started for the first time in Ukraine, have an important theoretical and practical consequence as this complex can be recommended as an active substance in iron-containing drugs with antianemic action. In conducting preclinical studies of new drugs, pathomorphological studies are important because they are a necessary step in studying the biological response of animals to the action of test substances. It was found that some pathological changes develop in the body of white mice under conditions of experimental acute and chronic iron (IV) clathrochelate intoxication. They correlated with the dose of the test compound. During chronic intoxication, the microscopic changes in the liver and kidney of white mice treated with iron (IV) clathrochelate at a dose of 1/10 DL50 were similar to the microscopic changes in the liver and kidney of mice treated with the experimental drug at a dose of 1/5 DL50. However, the severity of these changes was lower, reflecting a lower degree of organ damage. In the myocardium of mice treated with iron (IV) clathrochelate at a dose of 1/5 DL50 on the 10th day, as in acute iron (IV) clathrochelate poisoning, only edema was recorded. The prospects for further research are the study of microscopic changes in the organs of laboratory animals of other species during experimental iron (IV) clathrochelate toxicosis.

scholarly journals Arsenic speciation in food chains from mid-Atlantic hydrothermal vents

2012 ◽  
Vol 9 (2) ◽  
pp. 130 ◽  
Author(s):  
Vivien F. Taylor ◽  
Brian P. Jackson ◽  
Matthew R. Siegfried ◽  
Jana Navratilova ◽  
Kevin A. Francesconi ◽  
...  
Keyword(s):  
Stable Isotope ◽  
Deep Sea ◽  
Hydrothermal Vents ◽  
Arsenic Speciation ◽  
Inorganic Arsenic ◽  
Food Sources ◽  
Arsenic Compounds ◽  
Marine Animals ◽  
Δ13c And Δ15n ◽  
Organic Arsenic

Environmental contextArsenic occurs in marine organisms at high levels and in many chemical forms. A common explanation of this phenomenon is that algae play the central role in accumulating arsenic by producing arsenic-containing sugars that are then converted into simpler organic arsenic compounds found in fish and other marine animals. We show that animals in deep-sea vent ecosystems, which are uninhabited by algae, contain the same organic arsenic compounds as do pelagic animals, indicating that algae are not the only source of these compounds. AbstractArsenic concentration and speciation were determined in benthic fauna collected from the Mid-Atlantic Ridge hydrothermal vents. The shrimp species, Rimicaris exoculata, the vent chimney-dwelling mussel, Bathymodiolus azoricus, Branchipolynoe seepensis, a commensal worm of B. azoricus and the gastropod Peltospira smaragdina showed variations in As concentration and in stable isotope (δ13C and δ15N) signature between species, suggesting different sources of As uptake. Arsenic speciation showed arsenobetaine to be the dominant species in R. exoculata, whereas in B. azoricus and B. seepensis arsenosugars were most abundant, although arsenobetaine, dimethylarsinate and inorganic arsenic were also observed, along with several unidentified species. Scrape samples from outside the vent chimneys covered with microbial mat, which is a presumed food source for many vent organisms, contained high levels of total As, but organic species were not detectable. The formation of arsenosugars in pelagic environments is typically attributed to marine algae, and the pathway to arsenobetaine is still unknown. The occurrence of arsenosugars and arsenobetaine in these deep sea organisms, where primary production is chemolithoautotrophic and stable isotope analyses indicate food sources are of vent origin, suggests that organic arsenicals can occur in a foodweb without algae or other photosynthetic life.

scholarly journals Shifting the Specificity of E. coli Biosensor from Inorganic Arsenic to Phenylarsine Oxide through Genetic Engineering

Sensors ◽  
2020 ◽  
Vol 20 (11) ◽  
pp. 3093
Author(s):  
Hyojin Kim ◽  
Yangwon Jeon ◽  
Woonwoo Lee ◽  
Geupil Jang ◽  
Youngdae Yoon
Keyword(s):  
Genetic Engineering ◽  
Inorganic Arsenic ◽  
Arsenic Species ◽  
Coli Cell ◽  
Biological Processes ◽  
Phenylarsine Oxide ◽  
Covalent Bonds ◽  
E Coli ◽  
Organic Arsenic ◽  
The Moment

It has recently been discovered that organic and inorganic arsenics could be detrimental to human health. Although organic arsenic is less toxic than inorganic arsenic, it could form inorganic arsenic through chemical and biological processes in environmental systems. In this regard, the availability of tools for detecting organic arsenic species would be beneficial. Because As-sensing biosensors employing arsenic responsive genetic systems are regulated by ArsR which detects arsenics, the target selectivity of biosensors could be obtained by modulating the selectivity of ArsR. In this study, we demonstrated a shift in the specificity of E. coli cell-based biosensors from the detection of inorganic arsenic to that of organic arsenic, specifically phenylarsine oxide (PAO), through the genetic engineering of ArsR. By modulating the number and location of cysteines forming coordinate covalent bonds with arsenic species, an E. coli cell-based biosensor that was specific to PAO was obtained. Despite its restriction to PAO at the moment, it offers invaluable evidence of the potential to generate new biosensors for sensing organic arsenic species through the genetic engineering of ArsR.

Contribution of organic arsenic species to total arsenic measurements using ferrihydrite-backed diffusive gradients in thin films (DGT)

2012 ◽  
Vol 9 (1) ◽  
pp. 55 ◽  
Author(s):  
Heléne Österlund ◽  
Mikko Faarinen ◽  
Johan Ingri ◽  
Douglas C. Baxter
Keyword(s):  
Thin Films ◽  
Natural Waters ◽  
Arsenic Speciation ◽  
Inorganic Arsenic ◽  
Speciation Analysis ◽  
Arsenic Species ◽  
Future Studies ◽  
Organic Arsenic ◽  
Arsenic Determination ◽  
Diffusive Gradients

Environmental contextBoth the mobility and toxicity of arsenic in natural waters are related to the aqueous species distribution. Passive sampling using ferrihydrite-backed diffusive gradients in thin films (DGT) devices has in previous studies been characterised to measure labile inorganic arsenic, and the possible contribution of organic species has been disregarded. This study shows that the two most prevalent organic arsenic species might be included in DGT measurements, which should be taken into consideration when evaluating DGT data in future studies. AbstractIn previous publications discussing arsenic determination using ferrihydrite-backed diffusive gradients in thin films (DGT) devices, organic arsenic forms have been disregarded, even though it is known that the two most prevalent in natural waters, dimethylarsinate (DMA) and monomethylarsonate (MMA), may adsorb to ferrihydrite and thereby be included in the measurement. In this work the accumulation of DMA and MMA, as well as inorganic arsenite and arsenate, to ferrihydrite-backed DGT devices was investigated. It could be demonstrated that MMA, and under acidic conditions also DMA, adsorbed to the binding layer and might therefore contribute to the total mass of measured arsenic. Diffusion coefficients were measured for all four species to enable quantification of DGT-labile concentrations of organic and inorganic arsenic. Elution of the analytes from the ferrihydrite binding layer was performed using 1 mL of 1 M NaOH to facilitate arsenic speciation analysis using chromatographic separation. Average recovery rates were between 87 and 108 %. This study shows that the contribution of DMA and MMA to the total accumulated mass must be taken into consideration when evaluating DGT data in future studies.

Protective Role of Melatonin and Coenzyme Q10 in Ochratoxin A Toxicity in Rat Liver and Kidney

2007 ◽  
Vol 26 (1) ◽  
pp. 81-87 ◽  
Author(s):  
Emine Sutken ◽  
Erinc Aral ◽  
Filiz Ozdemir ◽  
Sema Uslu ◽  
Ozkan Alatas ◽  
...  
Keyword(s):  
Protective Effect ◽  
Ochratoxin A ◽  
Coenzyme Q ◽  
Kidney Tissue ◽  
Treated Group ◽  
Protective Role ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Liver And Kidney

Melatonin (MEL) and coenzyme Q10 (CoQ10) both display antioxidant and free radical scavenger properties. In the present study, the effect of MEL and CoQ10 on the oxidative stress and fibrosis induced by ochratoxin A (OTA) administration in rats was investigated. Rats were divided into five equal groups, each consisting of seven rats: (1) controls; (2) OTA-treated rats (289 μg/kg/day); (3) OTA+MEL–treated rats (289 μg/kg/day OTA + 10 mg/kg/day MEL); and (4) OTA+CoQ10–treated rats (289 μg/kg/day OTA +1 mg/100 g/day body weight (bw) CoQ10). After 4 weeks of treatment, the level of malondialdehyde (MDA), glutathione peroxidase (GPx), and hydroxyproline (Hyp) were measured in the homogenates of liver and kidney. In the OTA-treated group, the levels of MDA and Hyp in both liver and kidney were significantly increased when compared with the levels of control, whereas GPx activities decreased. In OTA+MEL–treated rats, the levels of MDA and Hyp in both liver and kidney were significantly decreased when compared with the levels of OTA-treated rats; however; GPX activities increased. In the OTA+CoQ10–treated group, the levels of MDA and Hyp were decreased when compared with the levels of OTA-treated rats, whereas GPx activities increased. In the OTA+CoQ 10–treated group, the levels of MDA, Hyp, and GPx were not significantly changed in kidney when compared with OTA-treated group. MEL has a protective effect against OTA toxicity through an inhibition of the oxidative damage and fibrosis both liver and kidney. Although CoQ10 has protective effect against OTA toxicity in liver tissue, it has no effect in kidney tissue.

scholarly journals Subchronic Oral Exposure to Prometryne Changes Relations of Blood Biochemistry Indicators in Mice

2009 ◽  
Vol 78 (2) ◽  
pp. 243-251 ◽  
Author(s):  
Domagoj Đikić ◽  
Vesna Benković ◽  
Anica Horvat-Knežević ◽  
Gordana Brozović ◽  
Nada Oršolić ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Cell Damage ◽  
Domestic Animal ◽  
Renal Tissue ◽  
Blood Biochemistry ◽  
Cultivated Plants ◽  
Oral Exposure ◽  
Triazine Herbicide ◽  
Different Doses

Prometryne is a methylthio-s-triazine herbicide used for the control of annual broadleaf and grass weeds in many cultivated plants. Significant traces are documented in the environment, mainly waters, soil and plants used for human and domestic animal nutrition. The aim of this study was to investigate whether prometryne, administered orally, could induce changes in metabolic patterns and cause cell damage in specific organs of exposed mice. Three different doses of prometryne (185, 375, 555 mg kg-1) were given per os repeatedly every 48 h, in a subchronic in vivo experimental design. After 28 days (14 doses), the correlations between the basic blood biochemistry indicators were analyzed (LDH, GGT, AlP, creatinine, ALT, AST). The increase in GGT and decrease in creatinine were the most distinct effects. LDH and AlP were increased, but rather explicitly in different dosage groups. ALT and AST did not change significantly, indicating that liver damage was milder than expected. Significant correlations between specific enzymes in renal tissue were lost in exposed groups. The correlations between muscle tissue specific enzymes were significant as a result of prometryne toxicity. Disbalance in relations between the serum indicators under study indicates that prometryne might have a myotoxic and nephrotoxic potential and the potential to affect enzymes and molecules important in normal metabolic pathways of bioenergetic physiology.

Organic Arsenic Lipid Derivatives Are More Potent and Less Toxic Than Inorganic Arsenic Trioxide in Preclinical Testing.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1803-1803 ◽  
Author(s):  
Xiaodong Cheng ◽  
Mirna Golemovic ◽  
Francis Giles ◽  
Ralph Zingaro ◽  
Ming-Zhang Gao ◽  
...  
Keyword(s):  
Arsenic Trioxide ◽  
Cell Lines ◽  
Membrane Integrity ◽  
Leukemia Cell ◽  
Inorganic Arsenic ◽  
Parp Cleavage ◽  
Potent Inducer ◽  
Intracellular Glutathione ◽  
Organic Arsenic

Abstract Arsenic trioxide (ATO) is an inorganic arsenic derivative that is effective in patients with relapsed acute promyelocytic leukemia. It is being investigated as therapy for other cancers but the risk/benefit ratio for its use still has to be determined due to its significant side effects. In contrast, organic arsenic derivatives are known to be much less toxic. We have synthesized a series of eight organic arsenic lipid derivatives and have tested them in NIH 60 cell line screen. Based on its activity, we selected GMZ27 [3-S-di(n-propyl)arsino-3-thio-1,2-propanediol] for further study in our laboratory and have confirmed its potent activity against human acute myeloid leukemia cell lines HL60 and NB4, which was significantly higher than that of arsenic trioxide. The IC50 (concentration that kills 50% of the cells) in MTS assay is 0.5 and 0.9 μm for GMZ27. Assessment of the mechanisms of action of GMZ27 in cell lines has shown that the GMZ27 was more potent inducer of superoxide than ATO. GMZ27 caused dissipation of mitochondrial transmembrane potential, cleavage of caspase 9, caspase 3 activation, PARP cleavage, and compromise in cell membrane integrity. However, its treatment also resulted in caspase 8 cleavage, suggesting that it affects both intrinsic and extrinsic apoptotic pathway. Its activity was related to the level of glutathione in the leukemic cells as pretreatment of the cells with BSO, which depletes intracellular glutathione, results in cells sensitivity to GMZ27. On the other hand, pretreatment with DDT, which increases intracellular glutathione, results in their resistance to GMZ27. GMZ27 had no effect on cells maturation and differentiation, and cell cycle. GMZ27 when tested against healthy donor mononuclear cells in a colony forming assay showed significantly less toxicity than arsenic trioxide. In vivo toxicity testing in Swiss Webster mice showed LD50 (dose that kills 50% of mice) to be 100 mg/kg for GMZ27, comparing to 10 mg/kg for ATO. In conclusion, organic arsenic lipid derivatives, and in particular GMZ27, may have more potent antileukemic activity and significantly less toxicity in vivo and in vitro than ATO and therefore further development of these medications is warranted.

Slow recovery from severe inorganic arsenic poisoning despite treatment with DMSA (2.3-dimercaptosuccinic acid)

2007 ◽  
Vol 45 (4) ◽  
pp. 424-428 ◽  
Author(s):  
Aud-E. Stenehjem ◽  
Marie Vahter ◽  
Barbro Nermell ◽  
Jorulf Aasen ◽  
Syverin Lierhagen ◽  
...  
Keyword(s):  
Inorganic Arsenic ◽  
Dimercaptosuccinic Acid ◽  
Slow Recovery ◽  
Arsenic Poisoning

Metabolomic study in plasma, liver and kidney of mice exposed to inorganic arsenic based on mass spectrometry

2014 ◽  
Vol 406 (5) ◽  
pp. 1455-1469 ◽  
Author(s):  
M. A. García-Sevillano ◽  
M. Contreras-Acuña ◽  
T. García-Barrera ◽  
F. Navarro ◽  
J. L. Gómez-Ariza
Keyword(s):  
Mass Spectrometry ◽  
Inorganic Arsenic ◽  
Liver And Kidney ◽  
Metabolomic Study

scholarly journals Comparative Effects of Phosphoenolpyruvate, a Glycolytic Intermediate, as an Organ Preservation Agent with Glucose and N-Acetylcysteine against Organ Damage during Cold Storage of Mouse Liver and Kidney

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Yoichi Ishitsuka ◽  
Yusuke Fukumoto ◽  
Yuki Kondo ◽  
Mitsuru Irikura ◽  
Daisuke Kadowaki ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Organ Preservation ◽  
Mouse Liver ◽  
Organ Damage ◽  
Histological Changes ◽  
Glycolytic Intermediate ◽  
Cold Preservation ◽  
Oxidative Stress Parameters ◽  
Liver And Kidney ◽  
And Oxidative Stress

We evaluated the usefulness of phosphoenolpyruvate (PEP), a glycolytic intermediate with antioxidative and energy supplementation potentials, as an organ preservation agent. Using ex vivo mouse liver and kidney of a static cold storage model, we compared the effects of PEP against organ damage and oxidative stress during cold preservation with those of glucose or N-acetylcysteine (NAC). Lactate dehydrogenase (LDH) leakage, histological changes, and oxidative stress parameters (measured as thiobarbituric acid reactive substance and glutathione content) were determined. PEP (100 mM) significantly prevented an increase in LDH leakage, histological changes, such as tubulonecrosis and vacuolization, and changes in oxidative stress parameters during 72 h of cold preservation in mouse liver. Although glucose (100 mM) partly prevented LDH leakage and histological changes, no effects against oxidative stress were observed. By contrast, NAC inhibited oxidative stress in the liver and did not prevent LDH leakage or histological changes. PEP also significantly prevented kidney damage during cold preservation in a dose-dependent manner, and the protective effects were superior to those of glucose and NAC. We suggest that PEP, a functional carbohydrate with organ protective and antioxidative activities, may be useful as an organ preservation agent in clinical transplantation.

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