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Unsal V, Keskin C, Oner E. Can quercetin reduce arsenic induced toxicity in mouse BALB/c 3T3 fibroblast cells? A study involving in vitro, molecular docking, and ADME predictions. BMC Pharmacol Toxicol 2025; 26:68. [PMID: 40133990 PMCID: PMC11934578 DOI: 10.1186/s40360-025-00906-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2024] [Accepted: 03/17/2025] [Indexed: 03/27/2025] Open
Abstract
This study aimed to investigate the protective effect of quercetin against arsenic-induced oxidative damage, inflammation, and apoptosis in mouse BALB/c 3T3 fibroblast cells (NIH-3T3). Arsenic at different concentrations of 0.05 µM (low), 0.5 µM (medium), 10 µM (high) doses were used to induce toxicity, while 120 μm quercetin was used for treatment. MTT and LDH analyses were performed to determine the effect of arsenic and quercetin on cell viability, while oxidative stress markers and antioxidant enzyme activities were measured by spectrophotometric method. TNF-α and IL-1β levels were measured by the ELISA method, Autodock programs were used for molecular docking studies. In addition, computer-based analyses of quercetin and succimer molecules were performed using SwissADME web tools. TNF-α (PDB ID: 2AZ5), IL-1β (PDB ID: 1ITB), Caspase3 (PDB ID: 2XYG), Bax (PDB ID: 4S0O), SOD (PDB ID:1CBJ), GSH-Px (PDB ID: 1GP1) and Bcl-2 (PDB ID: 1G5M) crystal structures were obtained from the Protein Data Bank. Bax and Bcl-2 levels of apoptotic genes and mRNA expression levels of Caspase-3 activity were measured using the QRT-PCR technique. TUNEL staining was performed to determine DNA fragmentations, while DAPI staining was done to visualise nuclear modifications. Quercetin has been found to significantly reduce oxidative stress, inflammation, and apoptosis in cells and exert anti-apoptotic effects. Molecular docking studies revealed quercetin shows good binding affinity with molecules with SOD, GSH-Px, Bax, Bcl-2, Caspase-3, TNF-α and IL-1β structures, and has been observed to bind with Bax and Bcl-2 with molecular docking scores of -7.5 and - 7.7 kcal/mol, respectively. These findings are supported by results showing that quercetin is effective in anti-apoptotic and anti-inflammatory processes in arsenic-induced cells under in vitro conditions. In addition, when ADME values are examined, it can be considered that quercetin is a useful and effective candidate compound in reducing arsenic toxicity, considering its higher synthetic accessibility score, better pharmacokinetic properties, and good biological transition and interaction capacities compared to succimer.
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Affiliation(s)
- Velid Unsal
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Mardin Artuklu University, Mardin, Türkiye.
| | - Cumali Keskin
- Department of Medical Services and Techniques, Vocational School of Health Services, Mardin Artuklu University, Mardin, Türkiye
| | - Erkan Oner
- Department of Biochemistry, Faculty of Pharmacy, Adıyaman University, Adıyaman, Türkiye
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Renu K, Mukherjee AG, Gopalakrishnan AV, Wanjari UR, Kannampuzha S, Murali R, Veeraraghavan VP, Vinayagam S, Paz-Montelongo S, George A, Vellingiri B, Madhyastha H. Protective effects of macromolecular polyphenols, metals (zinc, selenium, and copper) - Polyphenol complexes, and different organs with an emphasis on arsenic poisoning: A review. Int J Biol Macromol 2023; 253:126715. [PMID: 37673136 DOI: 10.1016/j.ijbiomac.2023.126715] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 08/28/2023] [Accepted: 09/03/2023] [Indexed: 09/08/2023]
Abstract
For the potential health benefits and nutritional value, polyphenols are one of the secondary metabolites of plants that have received extensive research. It has anti-inflammatory and cytotoxicity-reducing properties in addition to a high antioxidant content. Macromolecular polyphenols and polysaccharides are biologically active natural polymers with antioxidant and anti-inflammatory potential. Arsenic is an ecologically toxic metalloid. Arsenic in drinking water is the most common way people come into contact with this metalloid. While arsenic is known to cause cancer, it is also used to treat acute promyelocytic leukemia (APL). The treatment's effectiveness is hampered by the adverse effects it can cause on the body. Oxidative stress, inflammation, and the inability to regulate cell death cause the most adverse effects. Polyphenols and other macromolecules like polysaccharides act as neuroprotectants by mitigating free radical damage, inhibiting nitric oxide (NO) production, lowering A42 fibril formation, boosting antioxidant levels, and controlling apoptosis and inflammation. To prevent the harmful effects of toxins, polyphenols and pectin lower oxidative stress, boost antioxidant levels, improve mitochondrial function, control apoptosis, and suppress inflammation. Therefore, it prevents damage to the heart, liver, kidneys, and reproductive system. This review aims to identify the effects of the polyphenols in conjugation with polysaccharides as an ameliorative strategy for arsenic-induced toxicity in various organs.
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Affiliation(s)
- Kaviyarasi Renu
- Centre of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Dental College & Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, 600077, Tamil Nadu, India.
| | - Anirban Goutam Mukherjee
- Department of Biomedical Sciences, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu 632014, India.
| | - Abilash Valsala Gopalakrishnan
- Department of Biomedical Sciences, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu 632014, India.
| | - Uddesh Ramesh Wanjari
- Department of Biomedical Sciences, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu 632014, India.
| | - Sandra Kannampuzha
- Department of Biomedical Sciences, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu 632014, India.
| | - Reshma Murali
- Department of Biomedical Sciences, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu 632014, India.
| | - Vishnu Priya Veeraraghavan
- Centre of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Dental College & Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, 600077, Tamil Nadu, India.
| | - Sathishkumar Vinayagam
- Department of Biotechnology, Periyar University, Centre for Postgraduate and Research Studies, Dharmapuri 635205, Tamil Nadu, India.
| | - Soraya Paz-Montelongo
- Area de Toxicologia, Universidad de La Laguna, 38071 La Laguna, Tenerife, Islas Canarias, Spain; Grupo interuniversitario de Toxicología Alimentaria y Ambiental, Universidad de La Laguna, 38071 La Laguna, Tenerife, Islas Canarias, Spain.
| | - Alex George
- Jubilee Centre for Medical Research, Jubilee Mission Medical College and Research Institute, Thrissur, Kerala, India.
| | - Balachandar Vellingiri
- Stem cell and Regenerative Medicine/Translational Research, Department of Zoology, School of Basic Sciences, Central University of Punjab (CUPB), Bathinda 151401, Punjab, India.
| | - Harishkumar Madhyastha
- Department of Cardiovascular Physiology, Faculty of Medicine, University of Miyazaki, Miyazaki 889 1692, Japan.
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Singh RD, Koshta K, Tiwari R, Khan H, Sharma V, Srivastava V. Developmental Exposure to Endocrine Disrupting Chemicals and Its Impact on Cardio-Metabolic-Renal Health. FRONTIERS IN TOXICOLOGY 2022; 3:663372. [PMID: 35295127 PMCID: PMC8915840 DOI: 10.3389/ftox.2021.663372] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 05/10/2021] [Indexed: 01/12/2023] Open
Abstract
Developmental origin of health and disease postulates that the footprints of early life exposure are followed as an endowment of risk for adult diseases. Epidemiological and experimental evidence suggest that an adverse fetal environment can affect the health of offspring throughout their lifetime. Exposure to endocrine disrupting chemicals (EDCs) during fetal development can affect the hormone system homeostasis, resulting in a broad spectrum of adverse health outcomes. In the present review, we have described the effect of prenatal EDCs exposure on cardio-metabolic-renal health, using the available epidemiological and experimental evidence. We also discuss the potential mechanisms of their action, which include epigenetic changes, hormonal imprinting, loss of energy homeostasis, and metabolic perturbations. The effect of prenatal EDCs exposure on cardio-metabolic-renal health, which is a complex condition of an altered biological landscape, can be further examined in the case of other environmental stressors with a similar mode of action.
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Affiliation(s)
- Radha Dutt Singh
- Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada
| | - Kavita Koshta
- Systems Toxicology and Health Risk Assessment Group, Council of Scientific and Industrial Research-Indian Institute of Toxicology Research, Lucknow, India.,Academy of Scientific and Innovative Research, New Delhi, India
| | - Ratnakar Tiwari
- Feinberg Cardiovascular and Renal Research Institute, Feinberg School of Medicine, Northwestern University Chicago, Chicago, IL, United States
| | - Hafizurrahman Khan
- Systems Toxicology and Health Risk Assessment Group, Council of Scientific and Industrial Research-Indian Institute of Toxicology Research, Lucknow, India
| | - Vineeta Sharma
- Systems Toxicology and Health Risk Assessment Group, Council of Scientific and Industrial Research-Indian Institute of Toxicology Research, Lucknow, India
| | - Vikas Srivastava
- Systems Toxicology and Health Risk Assessment Group, Council of Scientific and Industrial Research-Indian Institute of Toxicology Research, Lucknow, India.,Academy of Scientific and Innovative Research, New Delhi, India
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Lu H, Zhao H, Wang Y, Guo M, Mu M, Liu Y, Nie X, Huang P, Xing M. Arsenic (III) induces oxidative stress and inflammation in the gills of common carp, which is ameliorated by zinc (II). J Inorg Biochem 2021; 225:111617. [PMID: 34571403 DOI: 10.1016/j.jinorgbio.2021.111617] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 09/09/2021] [Accepted: 09/16/2021] [Indexed: 12/13/2022]
Abstract
Arsenic (As) is widely present in the environment in form of arsenite (AsIII) and arsenate (AsV). Oxidative stress and inflammation are believed to be the dominant mechanisms of AsIII toxicity in vivo and in vitro. The aim of this study was to investigate whether zinc (Zn2+) alleviates exogenous gill toxicity in carp induced by AsIII and to gain insight into the underlying mechanisms. Exposure of carp to 2.83 mg As2O3/L for 30 days reduced superoxide dismutase activity by 4.0%, catalase by 41.0% and glutathione by 19.8%, while the concentration of malondialdehyde was increased by 16.4% compared to the control group, indicating oxidative stress. After the exposure of carp to AsIII the expression of inflammatory markers, such as interleukin-6, interleukin-8, tumor necrosis factor α and inducible nitric oxide synthase in gill tissue were significantly increased. In addition, the phosphorylation of nuclear factor kappa-B (NF-κB) was increased by 225%. 1 mg ZnCl2/L can relieve the toxicity of AsIII based on histopathology, antioxidase activity, qRT-PCR and western results. Zn2+ attenuated AsIII-induced gill toxicity that suppressed intracellular oxidative stress and NF-κB pathway by an upregulation of metallothionein. Therefore, the toxic effect of AsIII on the gill cells of carp was reduced. This study provides a theoretical basis for exploring the alleviation of the toxic effects of metalloids on organisms by heavy metals and the biological assessment of the effects.
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Affiliation(s)
- Hongmin Lu
- College of wildlife and protected area, Northeast Forestry University, Harbin 150040, Heilongjiang, PR China
| | - Hongjing Zhao
- College of wildlife and protected area, Northeast Forestry University, Harbin 150040, Heilongjiang, PR China
| | - Yu Wang
- College of wildlife and protected area, Northeast Forestry University, Harbin 150040, Heilongjiang, PR China
| | - Menghao Guo
- College of wildlife and protected area, Northeast Forestry University, Harbin 150040, Heilongjiang, PR China
| | - Mengyao Mu
- College of wildlife and protected area, Northeast Forestry University, Harbin 150040, Heilongjiang, PR China
| | - Yachen Liu
- College of wildlife and protected area, Northeast Forestry University, Harbin 150040, Heilongjiang, PR China
| | - Xiaopan Nie
- College of wildlife and protected area, Northeast Forestry University, Harbin 150040, Heilongjiang, PR China
| | - Puyi Huang
- College of wildlife and protected area, Northeast Forestry University, Harbin 150040, Heilongjiang, PR China.
| | - Mingwei Xing
- College of wildlife and protected area, Northeast Forestry University, Harbin 150040, Heilongjiang, PR China.
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Kerdsomboon K, Chumsawat W, Auesukaree C. Effects of Moringa oleifera leaf extracts and its bioactive compound gallic acid on reducing toxicities of heavy metals and metalloid in Saccharomyces cerevisiae. CHEMOSPHERE 2021; 270:128659. [PMID: 33757277 DOI: 10.1016/j.chemosphere.2020.128659] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/25/2020] [Revised: 09/26/2020] [Accepted: 10/15/2020] [Indexed: 05/07/2023]
Abstract
Moringa oleifera leaf extract is rich in antioxidants and has high potential for use to alleviate metal toxicity. Previously, we have reported the roles of aqueous M. oleifera leaf extract in mitigating intracellular cadmium (Cd) accumulation and Cd-induced oxidative stress. In this study, we investigated the protective role of aqueous and/or ethanolic M. oleifera leaf extracts (AMOLE and/or EMOLE) against other metal(loid)s in the eukaryotic model Saccharomyces cerevisiae. Our results show that only the AMOLE remarkably promoted the growth of yeast cells grown in the presence of arsenite (As(III)), Cd, nickel (Ni), and lead (Pb). Although the AMOLE contained lower amount of total phenolic and flavonoid contents and displayed lower DPPH scavenging capacity than the EMOLE, both AMOLE and EMOLE had the same capacity for reducing intracellular ROS levels in yeast cells exposed to As(III), Cd, Ni, and Pb. Moreover, the AMOLE was more effective than the EMOLE in inhibiting intracellular accumulation of these toxic metal(loid)s. In addition, we found that gallic acid, one of important phenolic constituents present in both extracts, could protect yeast cells against As(III) toxicity, likely through its role in decreasing As(III) accumulation and As(III)-induced ROS production. Furthermore, the hydroxyl and carboxyl groups of gallic acid appear to play a critical role in chelating As(III). The present study suggests the promising applications of the AMOLE (and also gallic acid) as protective agents against hazardous metal(loid)s.
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Affiliation(s)
- Kittikhun Kerdsomboon
- Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, Thailand
| | - Wisuta Chumsawat
- Department of Biotechnology, Faculty of Science, Mahidol University, Bangkok, Thailand; Mahidol University-Osaka University Collaborative Research Center for Bioscience and Biotechnology, Faculty of Science, Mahidol University, Bangkok, Thailand
| | - Choowong Auesukaree
- Department of Biotechnology, Faculty of Science, Mahidol University, Bangkok, Thailand; Mahidol University-Osaka University Collaborative Research Center for Bioscience and Biotechnology, Faculty of Science, Mahidol University, Bangkok, Thailand; Center of Excellence on Biodiversity, Bangkok, Thailand; Center of Excellence on Environmental Health and Toxicology, Bangkok, Thailand.
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Ugbaja RN, Akinhanmi TF, James AS, Ugwor EI, Babalola AA, Ezenandu EO, Ugbaja VC, Emmanuel EA. Flavonoid-rich fractions from Clerodendrum volubile and Vernonia amygdalina extenuates arsenic-invoked hepato-renal toxicity via augmentation of the antioxidant system in rats. CLINICAL NUTRITION OPEN SCIENCE 2021. [DOI: 10.1016/j.nutos.2020.12.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
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Kumar V, Akhouri V, Singh SK, Kumar A. Phytoremedial effect of Tinospora cordifolia against arsenic induced toxicity in Charles Foster rats. Biometals 2020; 33:379-396. [PMID: 33026605 DOI: 10.1007/s10534-020-00256-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Accepted: 09/30/2020] [Indexed: 10/23/2022]
Abstract
Arsenic poisoning is one of the most serious health hazards of recent times. It has been estimated that more than 200 million people of about 105 countries in the world are affected due to arsenic poisoning. Except mitigation, there is no such mode by which the population can be prevented from being exposed to arsenic. Tinospora cordifolia (T. cordifolia) is widely used in the folk medicine system for the treatment of various diseases. Hence, the aim of the present study was to investigate the antidote effects of ethanolic extract of T. cordifolia stem against arsenic induced hepato-renal toxicity in rat model. Twenty-four male Charles Foster rats (weighing 160-180 g) were randomly divided into two groups, where six rats were used as control group. Eighteen rats were orally treated with arsenic at the dose of 8 mg/kg body weight for 90 days daily and then further divided into three sub groups (n = 6 each). Sub group I-arsenic treated rats, were sacrificed after treatment; sub group II rats were used as arsenic control and the sub group III rats were administrated with T. cordifolia at the dose of 400 mg/kg body weight/day for 90 days. After the completion of dose duration, all the control and treatment group rats were sacrificed to evaluate the various parameters. Arsenic induced rats had significantly (p < 0.0001) altered biochemical serum levels of SGPT, SGOT, ALP, total bilirubin, urea, uric acid, creatinine and albumin; But, after the administration of T. cordifolia there was significant (p < 0.0001) restoration observed in these liver and kidney function parameters. The T. cordifolia administration also significantly (p < 0.0001) restored the serum MDA levels and arsenic concentration in blood, liver and kidney tissues, as well as significant (p < 0.0001) improvement in haematological variables. In histopathological study, the arsenic treated rats showed degenerative changes in the liver and kidney tissues such as lesions and vacuolizations in hepatocytes and nephrocytes respectively. However, after the administration with T. cordifolia rats, there was considerably significant restoration in liver and kidney tissues. The entire study suggests that arsenic caused severe damage to the liver and kidney at haematological, biochemical and histopathological levels in rats. However, T. cordifolia played the vital role to combat the arsenic induced toxicity in rats. Hence, T. cordifolia might be used as a nutritional supplement to combat the arsenic led toxicity among the exposed population.
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Affiliation(s)
- Vikas Kumar
- Anugrah Narayan College, Patna, Bihar, India
| | | | | | - Arun Kumar
- Mahavir Cancer Sansthan and Research Centre, Patna, Bihar, 801505, India.
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Zhao H, Wang Y, Guo M, Fei D, Mu M, Yu H, Xing M. Hepatoprotective effects of zinc (II) via cytochrome P-450/reactive oxygen species and canonical apoptosis pathways after arsenite waterborne exposure in common carp. CHEMOSPHERE 2019; 236:124869. [PMID: 31549675 DOI: 10.1016/j.chemosphere.2019.124869] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/05/2019] [Revised: 08/26/2019] [Accepted: 09/13/2019] [Indexed: 06/10/2023]
Abstract
Chronic arsenicosis has threatened the survival of aquatic animals with molecular mechanisms yet clear. In the present study, liver damage was evident by fluctuated activities of transaminases and declined ATPases in common carp under arsenic (As) exposure for 30 days. Mechanically, As significantly decreased cytochrome P-1A (CYP1A) activity and increased reactive oxygen species (ROS) content, which corroborated mitochondrial dysfunction in the hepatocytes. This hypothesis was further suggested by Caspase-3-executed apoptosis by death receptor pathway (Fas, TNF-α and Caspase-8) and mitochondrial pathway (Bax, Bcl-2 and Caspase-9). The above results indicated that As-elicited oxidative damage lead to apoptotic hepatic injury in carp. On the contrary, zinc (Zn) exerted an ROS scavenger and an antidote to As in the present model evidenced by alleviated liver injury and restored liver function index. Moreover, Zn and As co-administration displayed partially recovered CYPs enzyme system and quenched apoptotic positive cells compared As treated alone. These outcomes could be applied to develop counter practices based on Zn preparations to decrease the biotoxicity of As.
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Affiliation(s)
- Hongjing Zhao
- College of Wildlife and Protected Area, Northeast Forestry University, Harbin, 150040, Heilongjiang, PR China.
| | - Yu Wang
- College of Wildlife and Protected Area, Northeast Forestry University, Harbin, 150040, Heilongjiang, PR China.
| | - Menghao Guo
- College of Wildlife and Protected Area, Northeast Forestry University, Harbin, 150040, Heilongjiang, PR China
| | - Dongxue Fei
- College of Wildlife and Protected Area, Northeast Forestry University, Harbin, 150040, Heilongjiang, PR China
| | - Mengyao Mu
- College of Wildlife and Protected Area, Northeast Forestry University, Harbin, 150040, Heilongjiang, PR China
| | - Hongxian Yu
- College of Wildlife and Protected Area, Northeast Forestry University, Harbin, 150040, Heilongjiang, PR China.
| | - Mingwei Xing
- College of Wildlife and Protected Area, Northeast Forestry University, Harbin, 150040, Heilongjiang, PR China.
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Zhao H, Wang Y, Yang X, Fei D, Mu M, Guo M, Yu H, Xing M. Zinc alleviates arsenism in common carp: Varied change profiles of cytokines and tight junction proteins among two intestinal segments. FISH & SHELLFISH IMMUNOLOGY 2019; 94:761-768. [PMID: 31585240 DOI: 10.1016/j.fsi.2019.09.069] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Revised: 09/10/2019] [Accepted: 09/29/2019] [Indexed: 06/10/2023]
Abstract
This study was designed to evaluate the effects of zinc on inflammation and tight junction (TJ) in different intestinal regions of common carp under sub-chronic arsenic insult. Fish were exposed to zinc (0, 1 mg/L) and arsenic trioxide (0, 2.83 mg/L) in individual or combination for a month. Inflammatory infiltration and TJ structure changes were displayed by H&E staining and transmission electron microscope. To further explore these changes, biochemical indicator (SOD), gene or protein expressions of inflammatory responses (NF-κB, IL-1β, IL-6 and IL-8) and TJ proteins (Occludin, Claudins and ZOs) were determined. In the anterior intestine, arsenic decreased activity of SOD, mRNA levels of Occludin, Claudins and ZOs, increased mRNA levels of ILs. However, unlike the anterior intestine, arsenic has an upregulation effects of Occludin and Claudin-4 in the mid intestine. These anomalies induced by arsenic, except IL-8, were completely or partially recovered by zinc co-administration. Furthermore, transcription factor (NF-κB) nuclear translocation paralleled with its downstream genes in both intestinal regions. In conclusion, our results unambiguously suggested that under arsenic stress, zinc can partly relieve intestinal inflammation and disruption of tight junction segment-dependently.
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Affiliation(s)
- Hongjing Zhao
- College of Wildlife and Protected Area, Northeast Forestry University, Harbin, 150040, Heilongjiang, PR China.
| | - Yu Wang
- College of Wildlife and Protected Area, Northeast Forestry University, Harbin, 150040, Heilongjiang, PR China.
| | - Xin Yang
- College of Wildlife and Protected Area, Northeast Forestry University, Harbin, 150040, Heilongjiang, PR China
| | - Dongxue Fei
- College of Wildlife and Protected Area, Northeast Forestry University, Harbin, 150040, Heilongjiang, PR China
| | - Mengyao Mu
- College of Wildlife and Protected Area, Northeast Forestry University, Harbin, 150040, Heilongjiang, PR China
| | - Menghao Guo
- College of Wildlife and Protected Area, Northeast Forestry University, Harbin, 150040, Heilongjiang, PR China
| | - Hongxian Yu
- College of Wildlife and Protected Area, Northeast Forestry University, Harbin, 150040, Heilongjiang, PR China.
| | - Mingwei Xing
- College of Wildlife and Protected Area, Northeast Forestry University, Harbin, 150040, Heilongjiang, PR China.
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Mittal M, Chatterjee S, Flora SJS. Combination therapy with vitamin C and DMSA for arsenic-fluoride co-exposure in rats. Metallomics 2019; 10:1291-1306. [PMID: 30140832 DOI: 10.1039/c8mt00192h] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
INTRODUCTION Arsenic and fluoride are recognized globally as the most serious inorganic contaminants in drinking water. As there is no safe and effective treatment for the cases of fluoride poisoning and combined arsenic-fluoride toxicity, the present study was planned to assess (i) the mechanism of combined exposure to arsenic and fluoride via biochemical and spectroscopic data; (ii) the effect of a thiol chelating agent, meso-2,3-dimercaptosuccinic acid (DMSA), either individually or in combination with the antioxidant vitamin C in reversing arsenic-fluoride toxicity; and (iii) whether combination therapy enhances arsenic and fluoride removal from blood and soft tissues. METHODS Rats were exposed to arsenic (50 mg l-1) and fluoride (50 mg l-1) individually and in combination for 9 months and later administered DMSA (50 mg kg-1) via an i.p. route and vitamin C (25 mg kg-1) orally for 5 days. Biochemical parameters suggestive of alterations in the heme synthesis pathway, oxidative stress in blood, the liver and the kidneys, and concentrations of arsenic and fluoride in blood and soft tissues were studied. We also studied the infrared (IR) spectra of DNA extracted from the livers and kidneys of the normal and exposed animals. RESULTS It was found that chronic arsenic and fluoride exposure led to an increased oxidative stress condition and impaired heme synthesis (67% inhibition in δ-aminolevulinic acid dehydratase activity and 38% increase in δ-aminolevulinic acid synthetase activity). The decreased antioxidant defense mechanism was marked by a 2.25 fold increased concentration of Reactive Oxygen Species (ROS) and a 28% decrease in the Glutathione (GSH) level. Interestingly, concomitant exposure to arsenic and fluoride did not lead to antagonistic effects as the toxic effects were the same as those seen during the individual exposure to both the toxicants. It suggests that toxicity depends on the dose and duration of exposure. Combination therapy with DMSA and vitamin C showed a better efficacy than monotherapy in terms of reducing the arsenic and fluoride burden (more than 70% in blood and soft tissues) as well as reversal in the altered biochemical variables indicative of oxidative stress and tissue damage (80-85%). The infrared (IR) spectra of DNA isolated from the liver and kidneys suggested that the treatment with vitamin C and DMSA had no beneficial effects in terms of reversing DNA damage. CONCLUSION 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.
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Affiliation(s)
- Megha Mittal
- Defence Research and Development Establishment, Jhansi Road, Gwalior-474002, India
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Amadi CN, Offor SJ, Frazzoli C, Orisakwe OE. Natural antidotes and management of metal toxicity. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2019; 26:18032-18052. [PMID: 31079302 DOI: 10.1007/s11356-019-05104-2] [Citation(s) in RCA: 59] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/21/2019] [Accepted: 04/04/2019] [Indexed: 06/09/2023]
Abstract
The global burden of heavy metal especially mercury, arsenic, lead, and cadmium toxicities remains a significant public health challenge. Developing nations are particularly at high risk and carry the highest burden of this hazard. Chelation therapy has been the mainstay for treatment of heavy metal poisoning where the chelating agent binds metal ions to form complex ring-like structures called "chelates" to enhance their elimination from the body. Metal chelators have some drawbacks such as redistribution of some heavy metals from other tissues to the brain thereby increasing its neurotoxicity, causing loss of essential metals such as copper and zinc as well as some serious adverse effects, e.g., hepatotoxicity. The use of natural antidotes, which are easily available, affordable, and with little or no side effects compared to the classic metal chelators, is the focus of this review and suggested as cheaper options for developing nations in the treatment of heavy metal poisoning.
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Affiliation(s)
- Cecilia Nwadiuto Amadi
- Department of Experimental Pharmacology & Toxicology, Faculty of Pharmacy, University of Port-Harcourt, Port-Harcourt, Rivers State, Nigeria
| | - Samuel James Offor
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Uyo, Uyo, Akwa Ibom State, Nigeria
| | - Chiara Frazzoli
- Department of Cardiovascular and Endocrine-Metabolic Diseases, and Ageing, Istituto Superiore di Sanità (Italian National Institute of Health), Rome, Italy
| | - Orish Ebere Orisakwe
- Department of Experimental Pharmacology & Toxicology, Faculty of Pharmacy, University of Port-Harcourt, Port-Harcourt, Rivers State, Nigeria.
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Mónaco NM, Bartos M, Dominguez S, Gallegos C, Bras C, Esandi MDC, Bouzat C, Giannuzzi L, Minetti A, Gumilar F. Low arsenic concentrations impair memory in rat offpring exposed during pregnancy and lactation: Role of α7 nicotinic receptor, glutamate and oxidative stress. Neurotoxicology 2018; 67:37-45. [DOI: 10.1016/j.neuro.2018.04.011] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2018] [Revised: 04/09/2018] [Accepted: 04/15/2018] [Indexed: 10/17/2022]
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13
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Kushwaha P, Yadav A, Samim M, Flora SJS. Combinatorial drug delivery strategy employing nano-curcumin and nano-MiADMSA for the treatment of arsenic intoxication in mouse. Chem Biol Interact 2018; 286:78-87. [PMID: 29548727 DOI: 10.1016/j.cbi.2018.03.006] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Revised: 02/23/2018] [Accepted: 03/13/2018] [Indexed: 12/27/2022]
Abstract
Chelation therapy is the mainstream treatment for heavy metal poisoning. Apart from this, therapy using antioxidant/herbal extracts are the other strategies now commonly being tried for the treatment. We have previously reported individual beneficial efficacy of nanoparticle mediated administration of an antioxidant like 'curcumin' and an arsenic chelator 'monoisoamyl 2,3-dimercaptosuccinic acid (MiADMSA)' for the treatment of arsenic toxicity compared to bulk drugs. The present paper investigates our hypothesis that a combination drug delivery therapy employing two nanosystems, a chelator and a strong antioxidant, may produce more pronounced therapeutic effects compared to individual effects in the treatment of arsenic toxicity. An in-vivo study was conducted wherein arsenic as sodium arsenite (100 ppm) was administered in drinking water for 5 months to Swiss albino mice. This was followed by a treatment protocol comprising of curcumin encapsulated chitosan nanoparticles (nano-curcumin, 15 mg/kg, orally for 1 month) either alone or in combination with MiADMSA encapsulated polymeric nanoparticles (nano-MiADMSA, 50 mg/kg for last 5 days) to evaluate the therapeutic potential of the combination treatment. Our results demonstrated that co-treatment with nano-curcumin and nano-MiADMSA provided beneficial effects in a synergistic way on the adverse changes in oxidative stress parameters and metal status induced by arsenic.
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Affiliation(s)
- Pramod Kushwaha
- Division of Regulatory Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior 474002, M.P., India
| | - Abhishek Yadav
- Division of Regulatory Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior 474002, M.P., India
| | - M Samim
- Jamia Hamdard, New Delhi, India
| | - S J S Flora
- National Institute of Pharmaceutical Education and Research, Raebareli 209010, U.P., India.
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Rezaei M, Khodayar MJ, Seydi E, Soheila A, Parsi IK. Acute, but not Chronic, Exposure to Arsenic Provokes Glucose Intolerance in Rats: Possible Roles for Oxidative Stress and the Adrenergic Pathway. Can J Diabetes 2017; 41:273-280. [DOI: 10.1016/j.jcjd.2016.10.008] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2015] [Revised: 09/06/2016] [Accepted: 10/17/2016] [Indexed: 12/12/2022]
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Effect of curcumin on kidney histopathological changes, lipid peroxidation and total antioxidant capacity of serum in sodium arsenite-treated mice. ACTA ACUST UNITED AC 2017; 69:93-97. [DOI: 10.1016/j.etp.2016.08.006] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2016] [Accepted: 08/22/2016] [Indexed: 11/23/2022]
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16
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Ola-Davies OE, Akinrinde AS. Acute Sodium Arsenite-Induced Hematological and Biochemical Changes in Wistar Rats: Protective Effects of Ethanol Extract of Ageratum conyzoides. Pharmacognosy Res 2016; 8:S26-30. [PMID: 27114688 PMCID: PMC4821103 DOI: 10.4103/0974-8490.178645] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Background: Ageratum conyzoides L. (Asteraceae) is an annual herbaceous plant used in folklore medicine for the treatment of a wide range of diseases. Objective: To investigate the protective effect of the ethanol leaf extract of A. conyzoides (EEAC) against hematological, serum biochemical and histological alterations induced by Sodium arsenite administration to Wistar rats. Materials and Methods: Twenty male Wistar rats were randomly assigned into four groups of five rats each. Group I received propylene glycol and Group II rats were given the (EEAC, 100 mg/kg b.w.) orally for 7 days. Group III were given a single oral dose of sodium arsenite (NaAsO2, 2.5 mg/kg b.w.). Animals in Group IV were pretreated with 100 mg/kg EEAC for 7 days followed by a single oral dose of sodium arsenite. Results: Arsenic exposure resulted in significant reductions (P < 0.05) in values of packed cell volume (PCV), hemoglobin concentration (Hb) and red blood cell (RBC) count, and elevation in total white blood cell (WBC) count with insignificant reductions in serum total protein, albumin, and globulin levels. Alterations in aspartate aminotransferase, alanine transferase, alkaline phosphatase, and gamma glutamyl transferase activities, as well as in serum levels of urea, creatinine, glucose, cholesterol, and triglyceride levels, were not statistically significant. EEAC significantly restored (P < 0.05) the PCV, Hb, RBC, and WBC as well as serum albumin, globulin, and total protein to normal values. Conclusion: The results of this study indicate that EEAC possess strong potentials to protect against toxicities induced by sodium arsenite. SUMMARY
Ageratum conyzoides produced significant reversal of the reduction in the erythrocytic indices (packed cell volume, red blood cell, and Hb) caused by sodium arsenite Sodium arsenite-induced slight elevations in serum aspartate aminotransferase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP), correlating with the histopathological lesions observed Ageratum conyzoides produced only slight reductions in AST, ALT, and ALP compared to the sodium arsenite group, but significantly reduced the severity of histopathological lesions.
Abbreviations Used: EEAC: Ethanol extract of Ageratum conyzoides; RBC: Red blood cell; WBC: White blood cell; Hb: Hemoglobin; ALT: Alanine transaminase; AST: Aspartate transaminase or Aspartate aminotransferase; ALP: Alkaline phosphatase; GGT: Gamma glutamyl transferase.
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Affiliation(s)
- Olufunke Eunice Ola-Davies
- Department of Veterinary Physiology, Biochemistry and Pharmacology, Faculty of Veterinary Medicine, University of Ibadan, Ibadan, Oyo State, Nigeria
| | - Akinleye Stephen Akinrinde
- Department of Veterinary Physiology, Biochemistry and Pharmacology, Faculty of Veterinary Medicine, University of Ibadan, Ibadan, Oyo State, Nigeria
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Kumar M, Lalit M, Thakur R. Natural Antioxidants Against Arsenic-Induced Genotoxicity. Biol Trace Elem Res 2016; 170:84-93. [PMID: 26242483 DOI: 10.1007/s12011-015-0448-7] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2015] [Accepted: 07/15/2015] [Indexed: 01/30/2023]
Abstract
Arsenic is present in water, soil, and air in organic as well as in inorganic forms. However, inorganic arsenic is more toxic than organic and can cause many diseases including cancers in humans. Its genotoxic effect is considered as one of its carcinogenic actions. Arsenic can cause DNA strand breaks, deletion mutations, micronuclei formation, DNA-protein cross-linking, sister chromatid exchange, and DNA repair inhibition. Evidences indicate that arsenic causes DNA damage by generation of reactive free radicals. Nutritional supplementation of antioxidants has been proven highly beneficial against arsenic genotoxicity in experimental animals. Recent studies suggest that antioxidants protect mainly by reducing excess free radicals via restoring the activities of cellular enzymatic as well as non-enzymatic antioxidants and decreasing the oxidation processes such as lipid peroxidation and protein oxidation. The purpose of this review is to summarize the recent literature on arsenic-induced genotoxicity and its mitigation by naturally derived antioxidants in various biological systems.
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Affiliation(s)
- Munesh Kumar
- Guru Jambhehswar University of Science and Technology, Hisar, Haryana, India
| | - Minakshi Lalit
- Guru Jambhehswar University of Science and Technology, Hisar, Haryana, India
| | - Rajesh Thakur
- Guru Jambhehswar University of Science and Technology, Hisar, Haryana, India.
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Eskandari F, Momeni HR. Silymarin protects plasma membrane and acrosome integrity in sperm treated with sodium arsenite. Int J Reprod Biomed 2016. [DOI: 10.29252/ijrm.14.1.47] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
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Singh MK, Yadav SS, Yadav RS, Chauhan A, Katiyar D, Khattri S. Protective effect of Emblica-officinalis in arsenic induced biochemical alteration and inflammation in mice. SPRINGERPLUS 2015; 4:438. [PMID: 26312203 PMCID: PMC4545902 DOI: 10.1186/s40064-015-1227-9] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/31/2015] [Accepted: 08/10/2015] [Indexed: 12/21/2022]
Abstract
Exposure to arsenic in individuals has been found to be associated with immune related problems. In earlier studies, we have demonstrated that amla protects against arsenic induced oxidative stress and apoptosis in thymus and spleen of mice. In continuation to that the present study has therefore been focused to investigate the
protective efficacy of amla in arsenic induced inflammation and immunotoxicity in mice. The results showed that arsenic treatment significantly increased serum urea levels (69 %), glucose levels (48 %) and triglyceride levels (66 %) as compared to controls. Mice exposed to arsenic exhibited significant increased in TNF-α (4.3-fold), serum Interleukin-1 beta (threefold), Interleukin-6 (3.8-fold) as compared to controls. Arsenic exposure increased the relative frequency of CD8+ (Tc) cells sub-population (18.9 %) and decreased CD4+ (Th) cells (2.6 %). Arsenic exposure also significantly decreased T (CD3) and B (CD19) cells (21.1 %) as compared to controls. Simultaneously treatment with arsenic and amla significantly inhibited serum urea levels (47 %), glucose levels (50 %) and triglyceride levels (14 %). It also significantly decreased the TNF-α (1.1-fold), levels of IL-1β (1.6-fold), levels of Interleukin-6 (1.3-fold) in serum as compared to those treated with arsenic alone. Simultaneously treatment with arsenic and amla restored the alterations in CD8+ and CD4+ cells and also recovered the damages in B and T sub cells population. Results of the present study clearly indicate that arsenic induced immunotoxicity linked with inflammation has been significantly protected through simultaneous treatment with arsenic and amla that was due to anti-inflammatory and antioxidant activity of amla.
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Affiliation(s)
- Manish K Singh
- Department of Pharmacology, King George Medical University, Lucknow, 226 003 UP India
| | - Suraj Singh Yadav
- Department of Pharmacology, King George Medical University, Lucknow, 226 003 UP India
| | - Rajesh Singh Yadav
- Department of Criminology and Forensic Science, School of Applied Sciences, Dr. Harisingh Gour Central University, Sagar, 470 003 MP India
| | - Abhishek Chauhan
- Department of Pharmacology, King George Medical University, Lucknow, 226 003 UP India
| | - Devendra Katiyar
- Department of Pharmacology, King George Medical University, Lucknow, 226 003 UP India
| | - Sanjay Khattri
- Department of Pharmacology, King George Medical University, Lucknow, 226 003 UP India
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20
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Sankar P, Gopal Telang A, Kalaivanan R, Karunakaran V, Manikam K, Sarkar SN. Effects of nanoparticle-encapsulated curcumin on arsenic-induced liver toxicity in rats. ENVIRONMENTAL TOXICOLOGY 2015; 30:628-637. [PMID: 24347089 DOI: 10.1002/tox.21940] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/18/2013] [Revised: 12/02/2013] [Accepted: 12/05/2013] [Indexed: 06/03/2023]
Abstract
We investigated the therapeutic effectiveness of the nanoparticle-encapsulated curcumin (CUR-NP) against sodium arsenite-induced hepatic oxidative damage in rats. The CUR-NP prepared by emulsion technique was spherical in shape with an encapsulation efficiency of 86.5%. The particle size ranged between 120 and 140 nm with the mean particle size being 130.8 nm. Rats were divided into five groups of six each. Group 1 served as control. Group 2 rats were exposed to sodium arsenite (25 ppm) daily through drinking water for 42 days. Groups 3, 4, and 5 were treated with arsenic as in group 2, however, they were administered, empty nanoparticles, curcumin (100 mg/kg bw) and CUR-NP (100 mg/kg bw), respectively, by oral gavage during the last 14 days of arsenic exposure. Arsenic increased the activities of serum alanine aminotransferase and aspartate aminotransferase and caused histological alterations in liver indicating hepatotoxicity. Arsenic increased lipid peroxidation, depleted reduced glutathione and decreased the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase in liver. All these effects of arsenic were attenuated with both curcumin and CUR-NP. However, the magnitude of amelioration was more pronounced with CUR-NP. The results indicate that curcumin given in nano-encapsulated form caused better amelioration than free curcumin. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 628-637, 2015.
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Affiliation(s)
- Palanisamy Sankar
- Department of Veterinary Pharmacology and Toxicology, Veterinary College and Research Institute, Orathanadu, 614 625, Tamil Nadu, India
| | - Avinash Gopal Telang
- Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243 122, Bareilly, Uttar Pradesh, India
| | - Ramya Kalaivanan
- Department of Veterinary Epidemiology and Preventive Medicine, Veterinary College and Research Institute, Namakkal, 637002, Tamil Nadu, India
| | - Vijayakaran Karunakaran
- Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243 122, Bareilly, Uttar Pradesh, India
| | - Kesavan Manikam
- Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243 122, Bareilly, Uttar Pradesh, India
| | - Souvendra Nath Sarkar
- Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243 122, Bareilly, Uttar Pradesh, India
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Yadav A, Mathur R, Samim M, Lomash V, Kushwaha P, Pathak U, Babbar AK, Flora SJS, Mishra AK, Kaushik MP. Nanoencapsulation of DMSA monoester for better therapeutic efficacy of the chelating agent against arsenic toxicity. Nanomedicine (Lond) 2014; 9:465-81. [PMID: 24910877 DOI: 10.2217/nnm.13.17] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
AIMS Exposure to toxic metals remains a widespread occupational and environmental problem in world. Chelation therapy is a mainstream treatment used to treat heavy metal poisoning. This paper describes the synthesis, characterization and therapeutic evaluation of monoisoamyl 2,3-dimercaptosuccinic acid (MiADMSA)-encapsulated polymeric nanoparticles as a detoxifying agent for arsenic poisoning. MATERIALS & METHODS Polymeric nanoparticles entrapping the DMSA monoester, which can evade the reticulo-endothelial system and have a long circulation time in the blood, were prepared. Particle characterization was carried out by transmission electron microscopy and dynamic light scattering. An in vivo study was conducted to investigate the therapeutic efficacy of MiADMSA-encapsulated polymeric nanoparticles (nano- MiADMSA; 50 mg/kg orally for 5 days) and comparison drawn with bulk MiADMSA. Swiss albino mice exposed to sodium arsenite for 4 weeks were treated for 5 days to evaluate alterations in blood, brain, kidney and liver oxidative stress variables. The study also evaluated the histopathological changes in tissues and the chelating potential of the nanoformulation. RESULTS Our results show that nano-MiADMSA have a narrow size distribution in the 50-nm range. We observed an enhanced chelating potential of nano-MiADMSA compared with bulk MiADMSA as evident in the reversal of biochemical changes indicative of oxidative stress and efficient removal of arsenic from the blood and tissues. Histopathological changes and urinary 8-OHdG levels also prove better therapeutic efficacy of the novel formulation for arsenic toxicity. CONCLUSION The results from our study show better therapeutic efficacy of nano-MiADMSA in removing arsenic burden from the brain and liver.
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Sárközi K, Papp A, Horváth E, Máté Z, Ferencz Á, Hermesz E, Krisch J, Paulik E, Szabó A. Green tea and vitamin C ameliorate some neuro-functional and biochemical signs of arsenic toxicity in rats. Nutr Neurosci 2014; 19:102-9. [PMID: 25211010 DOI: 10.1179/1476830514y.0000000151] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND/OBJECTIVES Nervous system damage is one of the consequences of oral exposure to waterborne inorganic arsenic. In this work, the role of oxidative status in the neurotoxicity of arsenic and the possible role of two foodborne antioxidants in ameliorating arsenic-related oxidative stress were investigated. METHODS Male Wistar rats were given 10 mg/kg b.w. of trivalent inorganic arsenic (in the form of NaAsO2), 5 day/week for 6 weeks by gavage, combined with vitamin C solution (1 g/l) or green tea infusion (2.5 g in 500 ml boiled water) as antioxidants given in the drinking fluid. RESULTS Body weight gain was reduced by arsenic from the second week and the antioxidants had no effect on that. Cortical evoked potentials had increased latency, tail nerve conduction velocity was reduced, and this latter effect was counteracted by the antioxidants. The effect of green tea was stronger than that of vitamin C, and green tea also diminished lipid peroxidation induced by As. There was fair correlation between brain As levels, electrophysiological changes, and lipid peroxidation, suggesting a causal relationship. DISCUSSION Natural antioxidants might be useful in the protection of the central nervous system against the toxicity of oral As.
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Affiliation(s)
- Kitti Sárközi
- a Department of Public Health , University of Szeged Faculty of Medicine , Szeged , Hungary
| | - András Papp
- a Department of Public Health , University of Szeged Faculty of Medicine , Szeged , Hungary
| | - Edina Horváth
- a Department of Public Health , University of Szeged Faculty of Medicine , Szeged , Hungary
| | - Zsuzsanna Máté
- a Department of Public Health , University of Szeged Faculty of Medicine , Szeged , Hungary
| | - Ágnes Ferencz
- b Department of Biochemistry and Molecular Biology , University of Szeged Faculty of Science and Informatics , Szeged , Hungary
| | - Edit Hermesz
- b Department of Biochemistry and Molecular Biology , University of Szeged Faculty of Science and Informatics , Szeged , Hungary
| | - Judit Krisch
- c Institute of Food Engineering, University of Szeged Faculty of Engineering , Szeged , Hungary
| | - Edit Paulik
- a Department of Public Health , University of Szeged Faculty of Medicine , Szeged , Hungary
| | - Andrea Szabó
- a Department of Public Health , University of Szeged Faculty of Medicine , Szeged , Hungary
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Kulshrestha A, Jarouliya U, Prasad GBKS, Flora SJS, Bisen PS. Arsenic-induced abnormalities in glucose metabolism: Biochemical basis and potential therapeutic and nutritional interventions. World J Transl Med 2014; 3:96-111. [DOI: 10.5528/wjtm.v3.i2.96] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2014] [Revised: 06/21/2014] [Accepted: 07/17/2014] [Indexed: 02/05/2023] Open
Abstract
Health hazards due to the consumption of heavy metals such as arsenic have become a worldwide problem. Metabolism of arsenic produces various intermediates which are more toxic and cause toxicity. Arsenic exposure results in impairment of glucose metabolism, insulin secretion in pancreatic β-cells, altered gene expressions and signal transduction, and affects insulin-stimulated glucose uptake in adipocytes or skeletal muscle cells. Arsenic toxicity causes abnormalities in glucose metabolism through an increase in oxidative stress. Arsenic interferes with the sulfhydryl groups and phosphate groups present in various enzymes involved in glucose metabolism including pyruvate dehydrogenase and α-ketoglutarate dehydrogenase, and contributes to their impairment. Arsenic inhibits glucose transporters present in the cell membrane, alters expression of genes involved in glucose metabolism, transcription factors and inflammatory cytokines which stimulate oxidative stress. Some theories suggest that arsenic exposure under diabetic conditions inhibits hyperglycemia. However, the exact mechanism behind the behavior of arsenic as an antagonist or synergist on glucose homeostasis and insulin secretion is not yet fully understood. The present review delineates the relationship between arsenic and the biochemical basis of its relationship to glucose metabolism. This review also addresses potential therapeutic and nutritional interventions for attenuating arsenic toxicity. Several other potential nutritional supplements are highlighted in the review that could be used to combat arsenic toxicity.
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24
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Singh MK, Dwivedi S, Yadav SS, Sharma P, Khattri S. Arsenic-Induced Hepatic Toxicity and Its Attenuation by Fruit Extract of Emblica officinalis (Amla) in Mice. Indian J Clin Biochem 2014; 29:29-37. [PMID: 24478546 PMCID: PMC3903921 DOI: 10.1007/s12291-013-0353-9] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2013] [Accepted: 05/30/2013] [Indexed: 10/26/2022]
Abstract
Arsenic a metalloid and environmental contaminated has been found to be associated with public health problems in the affected areas. It is naturally occurred in groundwater and its accumulation in plant and animals leads to toxicity in several tissues most notably hepatic organ. Arsenic exposures (3 mg/kg body weight/day for 30 days) in mice exhibited increased arsenic and Zn levels in hepatocytes associated with enhanced oxidative stress in hepatocytes while there were no significantly changes were observed in Cu level. An increase in the lipid peroxidation and decrease in the levels of reduced glutathione and activity of superoxide dismutase, catalase, and glutathione peroxidase were observed in arsenic treated mice as compared to controls. Arsenic exposure in mice also caused a significant change in serum biomarkers in the SGOT, SGPT and creatinine as compared to the controls. There were no significant changes in the serum levels of total protein in these mice. Co-administration of arsenic and fruit extract of amla (500 mg/kg body weight/day for 30 days) caused a significant reduction of arsenic transference associated with significantly decreases hepatic arsenic levels and balanced the antioxidant enzyme and levels of serum hepatic enzymes like SGOT and SGPT. The results of the present study clearly demonstrate the antioxidant property of amla that could be responsible for its protective efficacy in arsenic induced hepatic toxicity.
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Affiliation(s)
- Manish K. Singh
- />Department of Pharmacology, King George’s Medical University, Lucknow, 226 003 India
| | - Shailendra Dwivedi
- />Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, 342005 India
| | - Suraj S. Yadav
- />Department of Pharmacology, King George’s Medical University, Lucknow, 226 003 India
| | - Praveen Sharma
- />Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, 342005 India
| | - Sanjay Khattri
- />Department of Pharmacology, King George’s Medical University, Lucknow, 226 003 India
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25
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Jiang Y, Wang L, Yao L, Liu Z, Gao H. Protective effect of edible marine algae, Laminaria japonica and Porphyra haitanensis, on subchronic toxicity in rats induced by inorganic arsenic. Biol Trace Elem Res 2013; 154:379-86. [PMID: 23842700 DOI: 10.1007/s12011-013-9739-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2013] [Accepted: 06/19/2013] [Indexed: 10/26/2022]
Abstract
Arsenic, a potent environmental toxic agent, causes various hazardous effects on human health. This study was performed to evaluate the protective effects of edible marine algae, Laminaria japonica and Porphyra haitanensis, on subchronic stress of rats induced by arsenic trioxide (As2O3). The co-treatment of marine algae could slightly increase the growth rates of body weights compared to the As2O3-treated group. The marine algae application restored liver and renal function by preventing the increment in the activities of alanine transaminase and alkaline phosphatase, and the levels of total protein, blood urea nitrogen, and creatinine. The increase in the contents of total cholesterol, triglyceride, and low density lipoprotein cholesterol, and decrease in the contents of high density lipoprotein cholesterol were observed in algae co-treated groups which indicated that marine algae could reverse the abnormal lipid metabolisms induced by arsenic. Moreover, these algae could protect the rats from lipid peroxidation by restoring the depletion of superoxide dismutase and glutathione peroxidase activities and sulfhydryl group contents, and lowering the enhanced malondialdehyde contents. Therefore, evidences indicate that L. japonica and P. haitanensis can serve as an effective regimen for treating arsenic poisoning.
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Affiliation(s)
- Yanhua Jiang
- Key Laboratory of Testing and Evaluation for Aquatic Product Safety and Quality, Ministry of Agriculture, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao, People's Republic of China
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Ram Kumar M, Flora SJS, Reddy GR. Monoisoamyl 2,3-dimercaptosuccinic acid attenuates arsenic induced toxicity: behavioral and neurochemical approach. ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY 2013; 36:231-242. [PMID: 23644418 DOI: 10.1016/j.etap.2013.03.019] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/06/2012] [Revised: 03/25/2013] [Accepted: 03/27/2013] [Indexed: 06/02/2023]
Abstract
Chronic exposure to arsenic in drinking water is associated with skin lesions, neurological effects, hypertension and high risk of cancer. The treatment in use at present employs administration of thiol chelators, such as meso-2,3-dimercaptosuccinic acid (DMSA) which are compromised with number of limitations due to their lipophobic nature. To address this problem, therapeutic efficacy of monoisoamyl meso-2,3-dimercaptosuccinic acid (MiADMSA), an analog of DMSA having lipophilic character, was examined against chronic arsenic poisoning in rats. Adult male Wistar rats were orally exposed to arsenic (2mg sodium arsenite/kg body weight) for 10 weeks followed by treatment with MiADMSA (50mg/kg, orally, once daily for 5 consecutive days). As-exposed rats showed significant differences in behavioral functions (open field behavior, total locomotor activity, grip strength and exploratory behavior) and water maze learning. Further, the biochemical studies performed on three brain regions (cerebellum, cortex and hippocampus) also showed significant elevation in malondialdehyde (MDA) levels with a concomitant decrease in the oxidative stress marker enzymes Mn-superoxide dismutase (Mn-SOD), Cu/Zn-superoxide dismutase (Cu/Zn-SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST). The alterations were more pronounced in cortex compared to cerebellum and hippocampus. The results showed that MiADMSA significantly reversed the As-induced alterations in behavior and biochemical variables suggestive of oxidative injury.
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Affiliation(s)
- M Ram Kumar
- Department of Biotechnology, Sri Venkateswara University, Tirupati, Andhra Pradesh, India
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Pineda J, Herrera A, Antonio MT. Comparison between hepatic and renal effects in rats treated with arsenic and/or antioxidants during gestation and lactation. J Trace Elem Med Biol 2013; 27:236-41. [PMID: 23339766 DOI: 10.1016/j.jtemb.2012.12.006] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2012] [Revised: 09/27/2012] [Accepted: 12/21/2012] [Indexed: 11/22/2022]
Abstract
The aim of this study was to determine whether biochemical changes occurred in the liver and kidney of arsenic (As) exposed pups during gestation and lactation, and investigate the potential beneficial role of antioxidants against arsenic exposure damage. Pregnant wistar rats received the following treatments as drinking water: (1) distilled water; (2) arsenic (50 mg/L); (3) antioxidants: zinc (20 mg/L)+vitamin C (2 g/L)+vitamin E (500 mg/L); (4) arsenic (50 mg/L)+antioxidants. As- intoxicated pups showed significant decreases in liver cholesterol and triglyceride concentration, whereas Aspartate aminotransferase (AST) and alkaline phosphatase (ALP) activities were increased. Treatment with antioxidants returns these values to control ones. TBARS production in both organs and liver glutathione peroxidase (GPx) activity also increased whereas catalase (CAT) activity in both organs decreased in arsenic-exposed pups; the antioxidant administration only recover TBARS concentration to control values. Our findings suggest that administration of antioxidants during gestation and lactation could prevent some of the negative effects of arsenic.
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Affiliation(s)
- Javier Pineda
- Department of Physiology (Animal Physiology II), Faculty of Biology, Complutense University, Madrid 28040, Spain
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Prasanna N, Krishnan DN, Rasool M. Sodium arsenite-induced cardiotoxicity in rats: protective role of p-coumaric acid, a common dietary polyphenol. Toxicol Mech Methods 2013. [PMID: 23194016 DOI: 10.3109/15376516.2012.748116] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
This study was performed to investigate the ameliorative role of p-coumaric acid against sodium arsenite-induced cardiotoxicity in rats. Sodium arsenite (5 mg/kg/b.wt) was orally administered once a day for 30 days to the animals to induce cardiotoxicity. After the experimental period, cardiotoxicity was assessed by estimating the levels of lipid peroxidation, anti-oxidant status (superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase, glutathione reductase, total reduced glutathione, protein sulfyhydryl and non-protein sulfhydryl groups) and DNA fragmentation in the cardiac tissue of control and experimental rats. In addition, cardiac tissue specific serum markers (triacylglycerides, total cholesterol, low-density lipoprotein cholesterol and high density lipoprotein cholesterol) in serum and histopathological changes in the cardiac tissue were also evaluated. From the results obtained in our study, sodium arsenite administration to the rats increased lipid peroxidation, DNA fragmentation, triacylglycerides, total cholesterol and low-density lipoprotein cholesterol, whereas antioxidant status and high-density lipoprotein cholesterol were found to be reduced. However, p-coumaric acid (75 and100 mg/kg/b.wt) treatment orally once per day for 30 days, immediately before a daily administration of sodium arsenite protected the abnormal biochemical abnormalities observed in the cardiac tissue of sodium arsenite treated rats as evidenced by the cardiac histopathology. For comparison purpose, a standard antioxidant vitamin C (100 mg/kg/b.wt) was used. In conclusion, this study concluded that p-coumaric acid could be a promising candidate for protecting the sodium arsenite-induced cardiotoxicity in rats through its antioxidant character.
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Affiliation(s)
- Nagalakshmi Prasanna
- Immunopathology Laboratory, School of Bio Sciences and Technology, VIT University, Vellore 632 014, Tamil Nadu, India
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Rajpoot DS, Prakash A, Mandil R, Rahal A, Garg SK. Differential modulation of xenobiotic-metabolizing enzymes in rats following single and concurrent exposure to chlorpyrifos, arsenic, and ascorbic acid. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH. PART A 2013; 76:1354-1365. [PMID: 24283477 DOI: 10.1080/15287394.2013.853005] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/02/2023]
Abstract
The present study was undertaken to evaluate the subacute toxicity of arsenic (As) and chlorpyrifos (CPF) alone or in combination. In addition, the ameliorative effect of ascorbic acid on As and/or CPF-induced hepatic microsomal xenobiotic metabolizing enzymes in rats was examined. Rats were divided into 9 groups of 6 animals each: control (deionized water), vehicle control (groundnut oil), ascorbic acid (100 mg/kg body weight), As (40 ppm in water), CPF (5 mg/kg body weight), As (40 ppm) + CPF (5 mg/kg body weight), As + ascorbic acid, CPF + ascorbic acid, and As + CPF + ascorbic acid. After 28 d of exposure, rats were sacrificed and liver was extracted for isolation of hepatic microsomes. Exposure to As or CPF alone as well as both of these in combination significantly altered microsomal proteins and activity of phase I and phase II xenobiotic-metabolizing enzymes. Cytochrome P-450 and cytochrome b 5 levels and activities of aniline p-hydroxylase (APH) and uridine diphosphate glucuronosyltransferase (UGT) were significantly decreased in groups treated with As, CPF, and As plus CPF, while glutathione S-transferase (GST) was not markedly altered. Enzymatic activity of aminopyrine N-demethylase (ANDM) was also significantly reduced in As- and CPF-only groups. Co-administration of ascorbic acid effectively countered the As- and CPF-induced alterations in xenobiotic-metabolizing enzymes.
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Affiliation(s)
- Dinesh Singh Rajpoot
- a Department of Pharmacology and Toxicology , College of Veterinary Science and Animal Husbandry, U. P. Pt. Deen Dayal Upadhyaya Veterinary and Animal Sciences University (DUVASU) , Mathura , India
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Dwivedi VK, Bhatanagar A, Chaudhary M. Protective role of ceftriaxone plus sulbactam with VRP1034 on oxidative stress, hematological and enzymatic parameters in cadmium toxicity induced rat model. Interdiscip Toxicol 2012; 5:192-200. [PMID: 23554563 PMCID: PMC3600523 DOI: 10.2478/v10102-012-0032-3] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2012] [Revised: 12/02/2012] [Accepted: 12/12/2012] [Indexed: 11/20/2022] Open
Abstract
We investigated the protective role of ceftriaxone plus sulbactam with VRP1034 (Elores) on hematological, lipid peroxidation, antioxidant enzymatic activities and Cd levels in the blood and tissues of cadmium exposed rats. Twenty-four male rats were divided into three groups of eight rats each. The control group received distilled water whereas group II received CdCl2 (1.5 mg/4 ml/body weight) through gastric gavage for 21 days. Group III received CdCl2 and was treated with ceftriaxone plus sulbactam with VRP1034 for 21 days. The hematological, biochemical, lipid peroxidation levels and enzymatic parameters were measured in plasma and tissues (brain, liver and kidney) of all groups. The Cd, Zn and Fe levels were measured in blood and tissues of all groups. Our findings showed significantly decreased cadmium (p<0.001), malonaldialdehyde (p<0.001) and myloperoxidase (MPO) levels along with significantly increased hemoglobin (p<0.01), RBC (p<0.05), hematocrit (p<0.05) levels and all antioxidant enzymatic activities (SOD, CAT, GR, GPx) in plasma and tissues of ceftriaxone plus sulbactam with VRP1034 treated group as compared to cadmium exposed group. Delta aminolevulinate dehydratase (δ-ALAD) activity was significantly (p<0.001) increased in the blood of ceftriaxone plus sulbactam with VRP1034 treated group as compared with cadmium exposed group. The levels of hepatic and renal parameters were significantly (p<0.001) decreased in ceftriaxone plus sulbactam with VRP1034 treated group as compared to cadmium exposed group. These findings indicate that ceftriaxone plus sulbactam with VRP1034 acts as a potent free radical scavenger and exhibits metal chelating properties that reduce free radical mediated tissue injury and prevent dysfunction of hepatic and renal organs during metal intoxication.
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Affiliation(s)
- Vivek Kumar Dwivedi
- Preclinical Divison, Venus Medicine Research Centre, Baddi, H.P. 173205 India
| | - Anuj Bhatanagar
- Analytical Division, Venus Medicine Research Centre, Baddi, H.P. 173205 India
| | - Manu Chaudhary
- Preclinical Divison, Venus Medicine Research Centre, Baddi, H.P. 173205 India
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Chaudhuri S, Acharya S, Chatterjee S, Kumar P, Singh MK, Bhattacharya D, Basu AK, Dasgupta S, Flora S, Chaudhuri S. Therapeutic Profile of T11TS vs. T11TS+MiADMSA: A Hunt for a More Effective Therapeutic Regimen for Arsenic Exposure. Asian Pac J Cancer Prev 2012; 13:2943-8. [DOI: 10.7314/apjcp.2012.13.6.2943] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
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Antonio Garcia MT, Herrera Dueñas A, Pineda Pampliega J. Hematological effects of arsenic in rats after subchronical exposure during pregnancy and lactation: the protective role of antioxidants. ACTA ACUST UNITED AC 2012; 65:609-14. [PMID: 22727912 DOI: 10.1016/j.etp.2012.06.004] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2011] [Revised: 03/26/2012] [Accepted: 06/04/2012] [Indexed: 12/14/2022]
Abstract
Free radicals production is involved in the toxicity of arsenic. The aim of this study was to determine whether biochemical changes occurred in the blood of arsenic-exposed pups during gestation and lactation, and additionally to investigate the potential beneficial role of the administration of certain antioxidants against arsenic exposure damage. Pregnant wistar rats received the following treatments as drinking water: (1) distilled water; (2) arsenic (50 mg/L); (3) antioxidants: zinc (20 mg/L)+vitamin C (2 g/L)+vitamin E (500 mg/L); (4) arsenic (50 mg/L)+antioxidants: zinc (20 mg/L)+vitamin C (2 g/L)+vitamin E (500 mg/L). We found a normocytic and normochromic anemia as well as a significant increase in hemolysis, TBARS production and catalase activity in the blood of arsenic intoxicated pups. Moreover, this metalloid produced a significant increase of serum cholesterol, triglicerids and urea levels whereas the proteins diminished. These effects were palliated in some extent by the coadministration of vitamins and zinc. Our findings suggest that administration of antioxidants during gestation and lactation could prevent some of the negative effects of arsenic.
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Staník R, Světlík J, Benkovský I. DMSA and its complexes with radioisotopes: review. J Radioanal Nucl Chem 2012. [DOI: 10.1007/s10967-012-1743-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
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Khan K, Wasserman GA, Liu X, Ahmed E, Parvez F, Slavkovich V, Levy D, Mey J, van Geen A, Graziano JH, Factor-Litvak P. Manganese exposure from drinking water and children's academic achievement. Neurotoxicology 2011; 33:91-7. [PMID: 22182530 DOI: 10.1016/j.neuro.2011.12.002] [Citation(s) in RCA: 158] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2011] [Revised: 11/21/2011] [Accepted: 12/02/2011] [Indexed: 02/02/2023]
Abstract
Drinking water manganese (WMn) is a potential threat to children's health due to its associations with a wide range of outcomes including cognitive, behavioral and neuropsychological effects. Although adverse effects of Mn on cognitive function of the children indicate possible impact on their academic achievement little evidence on this issue is available. Moreover, little is known regarding potential interactions between exposure to Mn and other metals, especially water arsenic (WAs). In Araihazar, a rural area of Bangladesh, we conducted a cross-sectional study of 840 children to investigate associations between WMn and WAs and academic achievement in mathematics and languages among elementary school-children, aged 8-11 years. Data on As and Mn exposure were collected from the participants at the baseline of an ongoing longitudinal study of school-based educational intervention. Annual scores of the study children in languages (Bangla and English) and mathematics were obtained from the academic achievement records of the elementary schools. WMn above the WHO standard of 400μg/L was associated with 6.4% score loss (95% CI=-12.3 to -0.5) in mathematics achievement test scores, adjusted for WAs and other sociodemographic variables. We did not find any statistically significant associations between WMn and academic achievement in either language. Neither WAs nor urinary As was significantly related to any of the three academic achievement scores. Our finding suggests that a large number of children in rural Bangladesh may experience deficits in mathematics due to high concentrations of Mn exposure in drinking water.
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Affiliation(s)
- Khalid Khan
- Columbia University Mailman School of Public Health, Department of Environmental Health Sciences, United States
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Kumar A, Nair P, Malhotra A, Majumdar S, Garg ML, Dhawan DK. Altered uptake and biological half-lives of 65Zn on arsenic exposure--modulation by zinc treatment. Biol Trace Elem Res 2011; 144:1059-1068. [PMID: 21647753 DOI: 10.1007/s12011-011-9101-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2011] [Accepted: 05/25/2011] [Indexed: 10/18/2022]
Abstract
The present study revealed the effects of zinc on the biokinetics of (65)Zn in rats following arsenic intoxication. The animals were segregated into four groups: group I--untreated controls, group II--arsenic treated (100 ppm as NaAsO(2) in drinking water), group III--zinc treated (227 mg ZnSO(4) per liter drinking water), and group IV--arsenic + zinc treated. Each rat was injected intraperitoneally with 1.85 MBq radioactivity of (65)Zn following 3 months of different treatments, and the radioactivity was determined using a suitably shielded scintillation counter. Arsenic treatment showed a significant increase in the fast component (Tb(1)) of the biological half-life of (65)Zn in liver, which remained unaltered in the whole body. Furthermore, arsenic treatment decreased significantly the slow component (Tb(2)) in the whole body, which remained unchanged in the liver. However, zinc supplementation to arsenic-treated rats normalized Tb(1) in the liver, but caused no change in Tb(2) in the whole body. Furthermore, the uptake values of (65)Zn were significantly increased in the liver, brain, kidney, and intestine following arsenic treatment, and the values in the liver and brain were decreased by zinc. Hence, zinc plays a significant role in regulating the biokinetics of (65)Zn in the liver and the whole body of arsenic-intoxicated rats.
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Affiliation(s)
- Ashok Kumar
- Department of Biophysics, Panjab University, Chandigarh, 160014, India
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Flora SJS. Arsenic-induced oxidative stress and its reversibility. Free Radic Biol Med 2011; 51:257-281. [PMID: 21554949 DOI: 10.1016/j.freeradbiomed.2011.04.008] [Citation(s) in RCA: 575] [Impact Index Per Article: 41.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2010] [Revised: 03/18/2011] [Accepted: 04/04/2011] [Indexed: 12/12/2022]
Abstract
This review summarizes the literature describing the molecular mechanisms of arsenic-induced oxidative stress, its relevant biomarkers, and its relation to various diseases, including preventive and therapeutic strategies. Arsenic alters multiple cellular pathways including expression of growth factors, suppression of cell cycle checkpoint proteins, promotion of and resistance to apoptosis, inhibition of DNA repair, alterations in DNA methylation, decreased immunosurveillance, and increased oxidative stress, by disturbing the pro/antioxidant balance. These alterations play prominent roles in disease manifestation, such as carcinogenicity, genotoxicity, diabetes, cardiovascular and nervous systems disorders. The exact molecular and cellular mechanisms involved in arsenic toxicity are rather unrevealed. Arsenic alters cellular glutathione levels either by utilizing this electron donor for the conversion of pentavalent to trivalent arsenicals or directly binding with it or by oxidizing glutathione via arsenic-induced free radical generation. Arsenic forms oxygen-based radicals (OH(•), O(2)(•-)) under physiological conditions by directly binding with critical thiols. As a carcinogen, it acts through epigenetic mechanisms rather than as a classical mutagen. The carcinogenic potential of arsenic may be attributed to activation of redox-sensitive transcription factors and other signaling pathways involving nuclear factor κB, activator protein-1, and p53. Modulation of cellular thiols for protection against reactive oxygen species has been used as a therapeutic strategy against arsenic. N-acetylcysteine, α-lipoic acid, vitamin E, quercetin, and a few herbal extracts show prophylactic activity against the majority of arsenic-mediated injuries in both in vitro and in vivo models. This review also updates the reader on recent advances in chelation therapy and newer therapeutic strategies suggested to treat arsenic-induced oxidative damage.
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Affiliation(s)
- Swaran J S Flora
- Division of Pharmacology & Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior 474002, India.
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Jain A, Yadav A, Bozhkov AI, Padalko VI, Flora SJS. Therapeutic efficacy of silymarin and naringenin in reducing arsenic-induced hepatic damage in young rats. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2011; 74:607-614. [PMID: 20719385 DOI: 10.1016/j.ecoenv.2010.08.002] [Citation(s) in RCA: 89] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/09/2010] [Revised: 07/27/2010] [Accepted: 08/01/2010] [Indexed: 05/29/2023]
Abstract
We investigated the effects of silymarin and naringenin in counteracting arsenic-induced hepatic oxidative stress post exposure. Male wistar rats were chronically exposed to sodium arsenite for eight months followed by oral treatment with silymarin and naringenin (50 mg/kg each) for 15 consecutive days to evaluate hepatic damage and antioxidant potential. Our results demonstrate a significant decrease in hepatic GSH levels, SOD and catalase activities and an increase in GST and TBARS levels after arsenic administration. Silymarin or naringenin administration increased GSH levels and was beneficial in the recovery of altered SOD and catalase activity besides significantly reducing blood and tissue arsenic concentration. Our results point to the antioxidant potential of these flavonoids, which might be of benefit in the clinical recovery of subject exposed to arsenic. These flavonoids can be incorporated into the diet or co-supplemented during chelation treatment, and thus may afford a protective effect against arsenite-induced cytotoxicity.
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Affiliation(s)
- Anshu Jain
- Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior 474 002, India
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Xi S, Guo L, Qi R, Sun W, Jin Y, Sun G. Prenatal and early life arsenic exposure induced oxidative damage and altered activities and mRNA expressions of neurotransmitter metabolic enzymes in offspring rat brain. J Biochem Mol Toxicol 2010; 24:368-78. [DOI: 10.1002/jbt.20349] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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Messarah M, Klibet F, Boumendjel A, Abdennour C, Bouzerna N, Boulakoud MS, El Feki A. Hepatoprotective role and antioxidant capacity of selenium on arsenic-induced liver injury in rats. ACTA ACUST UNITED AC 2010; 64:167-74. [PMID: 20851583 DOI: 10.1016/j.etp.2010.08.002] [Citation(s) in RCA: 118] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2010] [Revised: 06/30/2010] [Accepted: 08/10/2010] [Indexed: 11/30/2022]
Abstract
The present study was undertaken to evaluate the protective effect of selenium against arsenic-induced oxidative damage in experimental rats. Males were randomly divided into four groups where the first was served as a control, whereas the remaining groups were respectively treated with sodium selenite (3 mg/kg b.w.), sodium arsenite (5.55 mg/kg b.w.) and a combination of sodium arsenite and sodium selenite. Changes in liver enzyme activities, thiobarbituric acid reactive substances (TBARS) level, antioxidants and reduced glutathione (GSH) contents were determined after 3 weeks experimental period. Exposure of rats to As caused a significant increase in liver TBARS compared to control, but the co-administration of Se was effective in reducing its level. The activities of glutathione peroxidase (GPx) and glutathione-S-transferase (GST) of As-treated group were found lower compared to the control and the Se-treated group. The co-administration of Se had an additive protective effect on liver enzyme activities compared to As-treated animals. On the other hand, a significant increase in plasmatic activities of AST, ALT and ALP was observed in As-treated group. The latter was also exhibited a decrease in body weight and an increase in liver weight compared to the control. The co-administration of Se has decreased the activities of AST, AST and ALP and improved the antioxidant status as well. Liver histological studies have confirmed the changes observed in biochemical parameters and proved the beneficial role of Se. To conclude, results suggest that As exposure enhanced an oxidative stress by disturbing the tissue antioxidant defense system, but the Se co-administration protected liver tissues against As intoxication probably owing to its antioxidant properties.
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Affiliation(s)
- Mahfoud Messarah
- Animal Ecophysiology Laboratory, Faculty of Sciences, Badji Mokhtar University, BP 12 Sidi Amar, Annaba, Algeria.
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Rana T, Asit Kumar Bera, Das S, Pan D, Bandyopadhyay S, Bhattacharya D, De S, Subrata Kumar Das. Supplementation of ascorbic acid prevents oxidative damages in arsenic-loaded hepatic tissue of rat: An ex vivo study. Hum Exp Toxicol 2010; 29:965-72. [DOI: 10.1177/0960327110364641] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Oxidative stress due to arsenic toxicity and ameliorative potentiality of L-ascorbic acid was evaluated in an ex vivo system of rat hepatic tissue. The study revealed that arsenic increased the activity of superoxide dismutase (SOD) and catalase (CAT) and the level of lipid peroxidation (LPO), protein carbonyl (PC) and nitric oxide (NO) at 1 hour, 1.5 hours and 2 hours of incubation. Co-treatment with L-ascorbic acid was found effective to normalize the activity of SOD and CAT and the production of LPO, PC and NO in hepatic tissue. This ex vivo study suggested that ascorbic acid is helpful to ameliorate arsenic-induced oxidative stress. This may be one of the alternative screening systems to study the efficacy of antioxidant and hepatoprotective agent.
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Affiliation(s)
- Tanmoy Rana
- Indian Veterinary Research Institute, Kolkata, India
| | | | | | - Diganta Pan
- Indian Veterinary Research Institute, Kolkata, India
| | | | | | - Sumanta De
- Indian Veterinary Research Institute, Kolkata, India
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Bera AK, Rana T, Das S, Bandyopadhyay S, Bhattacharya D, Pan D, De S, Das SK. L-Ascorbate protects rat hepatocytes against sodium arsenite--induced cytotoxicity and oxidative damage. Hum Exp Toxicol 2009; 29:103-11. [PMID: 20028703 DOI: 10.1177/0960327109357215] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Sodium arsenite-exposed hepatocytes of rat showed higher production of nitric oxide (NO) and increased lipid peroxidation (LPO) level vis-a-vis activity of superoxide dismutase (SOD) and catalase (CAT) were significantly lowered. Subsequently, the cell proliferation index (CPI) and cell viability were also reduced. Treatment with L-ascorbate was found effective in normalizing the arsenic-induced alteration of SOD and CAT activity and LPO level in rat hepatocytes. These observations indicated that L-ascorbate also has potent cytoprotective role as it could reduce the NO production and normalize the cell proliferation and viability of hepatocytes. Therefore, the in vitro study suggested that ascorbic acid is helpful to ameliorate the arsenic-induced cytotoxicity and oxidative stress of rat hepatocytes.
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Affiliation(s)
- Asit Kumar Bera
- Indian Veterinary Research Institute, Eastern Regional Station, Kolkata, India.
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Kumar P, Prasad Y, Patra AK, Ranjan R, Swarup D, Patra RC, Pal S. Ascorbic acid, garlic extract and taurine alleviate cadmium-induced oxidative stress in freshwater catfish (Clarias batrachus). THE SCIENCE OF THE TOTAL ENVIRONMENT 2009; 407:5024-5030. [PMID: 19552941 DOI: 10.1016/j.scitotenv.2009.05.030] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/08/2009] [Revised: 05/04/2009] [Accepted: 05/20/2009] [Indexed: 05/28/2023]
Abstract
An experiment was conducted to investigate bioaccumulation potential of cadmium (Cd) and changes in oxidative stress indices in liver and kidney tissues from Cd-exposed catfish (Clarias batrachus) with or without simultaneous treatment of water with ascorbic acid, garlic extract or taurine. C. batrachus (n=324) with average length of 20+/-4 cm and weight of 86+/-5 g were used for the present investigation. Fishes were divided into nine groups (I to IX) each comprising 36 fishes. The fishes of groups II, III, IV and V were challenged with 5 ppm of cadmium chloride monohydrate (CdCl2.H2O), whereas groups VI, VII, VIII and IX were exposed to 10 ppm CdCl2.H2O solution for a period of 45 days. Group I was kept as negative control and the fishes of this group were maintained in water containing no added Cadmium. Group II and VI were maintained as Cd exposed non treated control to serve as positive controls. Fishes of III and VII, IV and VIII, V and IX received ascorbic acid (5 ppm), extract of dried garlic (5 ppm) or taurine (5 ppm), respectively during the entire experiment period. The concentrations of Cd in liver and kidney increased significantly following exposure to Cd and the level continued to rise with the increase in exposure duration. Treatment of tank water with ascorbic acid, garlic or taurine significantly reduced the Cd concentrations in tissues compared to the positive control group, but the level in Cd exposed groups was greater than the negative control group. Fishes exposed to Cd and treated with ascorbic acid, garlic or taurine had reduced oxidative stress as evidenced from lower concentration of lipid peroxides and higher activities of superoxide dismutase and catalase in liver, kidney and erythrocytes compared to fishes exposed to Cd. The reduction in Cd induced oxidative stress was highest in ascorbic acid treated group followed by garlic and taurine treatment. The results suggest that ascorbic acid, garlic and taurine have potential to reduce tissue accumulation of Cd and associated oxidative stress in freshwater catfish.
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Affiliation(s)
- Puneet Kumar
- Aquatic Biotechnology and Fish Pathology Laboratory, Department of Animal Science, M.J.P. Rohilkhand University, Bareilly-243 006, India.
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Co-administration of α-Lipoic Acid and Vitamin C Protects Liver and Brain Oxidative Stress in Mice Exposed to Arsenic Contaminated Water. ACTA ACUST UNITED AC 2009. [DOI: 10.1007/s12403-009-0013-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Flora SJS, Mehta A, Gupta R. Prevention of arsenic-induced hepatic apoptosis by concomitant administration of garlic extracts in mice. Chem Biol Interact 2009; 177:227-233. [PMID: 18834867 DOI: 10.1016/j.cbi.2008.08.017] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2008] [Revised: 08/28/2008] [Accepted: 08/28/2008] [Indexed: 10/21/2022]
Abstract
Garlic is well known as a folk remedy for a variety of ailments since ancient times, however, very few studies are available suggesting its beneficial role against arsenic toxicity pertaining to its ability to eliminate arsenic from the blood and soft tissues and in reversal of arsenic-induced oxidative stress in affected tissues. The present study was planned to investigate the protective efficacy of aqueous garlic extract using two different doses on parameters suggestive of hepatic injury, tissue oxidative stress and mobilization of arsenic. Further, an attempt to understand the mechanism of arsenic in inducing hepatic apoptosis was also studied. Results of the present study suggested that arsenic administration in mice caused generation of reactive oxygen species (ROS) causing apoptosis through mitochondria-mediated pathway. The ROS generation in hepatic tissue reverted to normal values after co-administration of garlic extracts. The study provides significant evidence that garlic extracts contain strong anti-oxidant property which could be beneficial in preventing arsenic-induced toxicity in cells. However, further research is required to determine whether the results from animal studies are applicable to humans before garlic can be recommended as a putative agent against arsenic toxicity.
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Affiliation(s)
- Swaran J S Flora
- Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior 474002, India.
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46
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Xi S, Sun W, Wang F, Jin Y, Sun G. Transplacental and early life exposure to inorganic arsenic affected development and behavior in offspring rats. Arch Toxicol 2009; 83:549-56. [DOI: 10.1007/s00204-009-0403-5] [Citation(s) in RCA: 65] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2008] [Accepted: 01/15/2009] [Indexed: 11/29/2022]
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47
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Bardullas U, Limón-Pacheco JH, Giordano M, Carrizales L, Mendoza-Trejo MS, Rodríguez VM. Chronic low-level arsenic exposure causes gender-specific alterations in locomotor activity, dopaminergic systems, and thioredoxin expression in mice. Toxicol Appl Pharmacol 2008; 239:169-77. [PMID: 19121333 DOI: 10.1016/j.taap.2008.12.004] [Citation(s) in RCA: 81] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2008] [Revised: 11/26/2008] [Accepted: 12/04/2008] [Indexed: 11/25/2022]
Abstract
Arsenic (As) is a toxic metalloid widely present in the environment. Human exposure to As has been associated with the development of skin and internal organ cancers and cardiovascular disorders, among other diseases. A few studies report decreases in intelligence quotient (IQ), and sensory and motor alterations after chronic As exposure in humans. On the other hand, studies of rodents exposed to high doses of As have found alterations in locomotor activity, brain neurochemistry, behavioral tasks, and oxidative stress. In the present study both male and female C57Bl/6J mice were exposed to environmentally relevant doses of As such as 0.05, 0.5, 5.0, or 50 mg As/L of drinking water for 4 months, and locomotor activity was assessed every month. Male mice presented hyperactivity in the group exposed to 0.5 mg As/L and hypoactivity in the group exposed to 50 mg As/L after 4 months of As exposure, whereas female mice exposed to 0.05, 0.5, and 5.0 mg As/L exhibited hyperactivity in every monthly test during As exposure. Furthermore, striatal and hypothalamic dopamine content was decreased only in female mice. Also decreases in tyrosine hydroxylase (TH) and cytosolic thioredoxin (Trx-1) mRNA expression in striatum and nucleus accumbens were observed in male and female mice, respectively. These results indicate that chronic As exposure leads to gender-dependent alterations in dopaminergic markers and spontaneous locomotor activity, and down-regulation of the antioxidant capacity of the brain.
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Affiliation(s)
- U Bardullas
- Departamento de Neurobiología Conductual y Cognitiva, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Boulevard Juriquilla 3001, Querétaro, Querétaro 76230, México
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48
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Mishra D, Flora SJS. Quercetin administration during chelation therapy protects arsenic-induced oxidative stress in mice. Biol Trace Elem Res 2008; 122:137-47. [PMID: 18183357 DOI: 10.1007/s12011-007-8064-9] [Citation(s) in RCA: 48] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2007] [Revised: 10/25/2007] [Accepted: 11/27/2007] [Indexed: 01/12/2023]
Abstract
We studied the efficacy of quercetin and a thiol chelating agent, monoisoamyl 2, 3-dimercaptosuccinic acid (MiADMSA) either individually or in combination against arsenic-induced oxidative stress and mobilization of metal in mouse. Animals were chronically exposed to 25 ppm arsenite as sodium arsenite in drinking water for 12 months followed by treatment with MiADMSA (0.2 mmol/kg, orally), quercetin (0.2 mmol, orally) either alone or in combination, once daily for 5 consecutive days. Arsenic exposure led to a significant depletion of blood delta-aminolevulinic acid dehydratase (ALAD) activity, glutathione, white (WBC) and red blood cell (RBC) counts, and an increase in platelet levels while significantly increasing the level of reactive oxygen species (in RBCs). Hepatic reduced catalase (CAT) and glutathione peroxidase activities showed a depletion, whereas thiobarbituric acid reactive substances (TBARS) levels increased on arsenic exposure indicating arsenite-induced oxidative stress in blood and liver. Kidney CAT activity showed a depletion, whereas TBARS levels increased on arsenic exposure. These biochemical changes were accompanied by an increase in blood, liver, and kidney arsenic concentration. Treatment with MiADMSA was effective in increasing ALAD activity, whereas quercetin was ineffective when given alone. Quercetin when co-administered with MiADMSA also provided no additional beneficial effect on blood ALAD activity but significantly brought altered platelet counts nearer to the normal value. In contrast, administration of quercetin alone provided significant beneficial effects on hepatic oxidative stress and kidney TBARS levels. Renal biochemical variables remained insensitive to arsenic and any of the treatments. Interestingly, combined administration of quercetin with MiADMSA had a remarkable effect in depleting total arsenic concentration from blood and soft tissues. These results lead us to conclude that quercetin administration during chelation treatment had some beneficial effects particularly on the protection of inhibited blood ALAD activity and depletion of arsenic level from target organs. The study supports our earlier conclusion that a co-administration of an antioxidant particularly flavonoids more beneficial than monotherapy with the chelating agents to achieve optimal effects of chelation in arsenite toxicity.
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Affiliation(s)
- Deepshikha Mishra
- Division of Pharmacology and Toxicology, Defense Research and Development Establishment, Jhansi Road, Gwalior, 474 002, India
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Mishra D, Flora SJS. Differential oxidative stress and DNA damage in rat brain regions and blood following chronic arsenic exposure. Toxicol Ind Health 2008; 24:247-56. [DOI: 10.1177/0748233708093355] [Citation(s) in RCA: 49] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Chronic arsenic poisoning caused by contaminated drinking water is a wide spread and worldwide problem particularly in India and Bangladesh. One of the possible mechanisms suggested for arsenic toxicity is the generation of reactive oxygen species (ROS). The present study was planned 1) to evaluate if chronic exposure to arsenic leads to oxidative stress in blood and brain – parts of male Wistar rats and 2) to evaluate which brain region of the exposed animals was more sensitive to oxidative injury. Male Wistar rats were exposed to arsenic (50 ppm sodium arsenite in drinking water) for 10 months. The brain was dissected into five major parts, pons medulla, corpus striatum, cortex, hippocampus, and cerebellum. A number of biochemical variables indicative of oxidative stress were studied in blood and different brain regions. Single-strand DNA damage using comet assay was also assessed in lymphocytes. We observed a significant increase in blood and brain ROS levels accompanied by the depletion of GSH/GSSG ratio and glucose-6-phosphate dehydrogenase (G6PD) activity in different brain regions of arsenic-exposed rats. Chronic arsenic exposure also caused significant single-strand DNA damage in lymphocytes as depicted by comet with a tail in arsenic-exposed cells compared with the control cells. On the basis of results, we concluded that the cortex region of the brain was more sensitive to oxidative injury compared with the other regions studied. The present study, thus, leads us to suggest that arsenic induces differential oxidative stress in brain regions with cortex followed by hippocampus and causes single-strand DNA damage in lymphocytes.
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Affiliation(s)
- D Mishra
- Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior, India
| | - SJS Flora
- Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior, India
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Flora SJS, Gupta R. Beneficial effects of Centella asiatica aqueous extract against arsenic-induced oxidative stress and essential metal status in rats. Phytother Res 2007; 21:980-988. [PMID: 17600859 DOI: 10.1002/ptr.2208] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
The efficacy of an aqueous extract of Centella asiatica (100, 200 and 500 mg/kg for 5 consecutive days) was studied in the depletion of arsenic and in the recovery of a few altered biochemical variables in arsenic pre-exposed rats (20 ppm in drinking water for 5 weeks). Exposure to arsenic significantly depleted delta-aminolevulinic acid dehydratase (ALAD) activity, reduced glutathione (GSH) level, superoxide dismutase (SOD) and increased thiobarbituric acid reactive substance (TBARS) activity in red blood cells. Significant depletion of ALAD activity, GSH level, glutathione peroxidase (GPx), SOD and catalase (CAT) activities and an increase in TBARS levels in liver tissues was also noted. There was a significant depletion of SOD, CAT and GPx activities in kidneys and an increased TBARS levels in kidney and brain accompanied by increased arsenic concentration in blood and soft tissues. Treatment with aqueous extract of Centella asiatica provided significant protection against ALAD, GSH and TBARS levels, particularly at doses of 200 and 500 mg. Centella asiatica also provided significant recovery in the inhibited liver ALAD and G6PD activities. Arsenic concentration in blood and soft tissues remained uninfluenced after Centella asiatica administration. The present study thus suggests a beneficial effect of Centella asiatica against arsenic-induced oxidative stress but possesses no chelating property.
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Affiliation(s)
- S J S Flora
- Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior 474002, India.
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