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Levosimendan (LEVO) is a calcium sensitizer with established inotropic and vasodilator impacts associated with ATP-sensitive potassium channels (KATP). Although LEVO's role in modulating oxidative stress of cardiac cells has been studied, in the current study, LEVO was used, for the first time, to investigate its preventive and therapeutic roles in pancreatic islets through viability, functionality, and inflammation pathways as well as oxidative stress against the toxicity induced by sodium arsenite (NaAsO2). Following the optimization studies to select the proper concentrations of LEVO and NaAsO2, isolated pancreatic islets were exposed to different combinations of NaAsO2 and LEVO. MTT assay, glucose-dependent insulin secretion test, investigation of oxidative stress and inflammation biomarkers in addition to qualification of the expressions of P16, P38, and NF-κB genes were performed to assess different underlying mechanisms to investigate the protective role of LEVO against NaAsO2-induced toxicity. This study demonstrated that NaAsO2-treated pancreatic islets' exposure to LEVO improved their viability and functionality while modulating the generation of oxidative stress and inflammatory biomarkers. Therefore LEVO caused significant recoveries in the characteristics of the islets. The main conclusion is that LEVO showed protective impacts in pancreatic islets against exposure to NaAsO2. However, therapeutic uses of LEVO in the field of diabetes need further investigations. Sodium arsenite is responsible for activating the oxidative stress and inflammation pathways in pancreatic islet cells and consequently decreasing their viability and function. Treatment of pancreatic islets with sodium arsenite results in the loss of glucose-dependent insulin secretion (GDIS) which can be alleviated by levosimendan. Levosimendan modulates the decreased level of secreted insulin by preventing formation of reactive oxygen species (ROS) and inactivating the inflammatory biomarkers. Levosimendan improves the viability and function of sodium arsenite-treated pancreatic islets by modulating insulin secretion and glucose control. Levosimendan acts as a protective agent against the toxicity induced by sodium arsenite in pancreatic islets through modulating the viability, oxidative stress, inflammation, and function pathways. [ABSTRACT FROM AUTHOR]

This study was designed to investigate the potential protective effect of lycopene (Lyc) against arsenic-induced nephrotoxicity. Sodium arsenite orally administered to mice for 14 days, inducing severe nephrotoxicity, in the form of hyponatremia, hyperkalemia, and elevation in the markers of kidney damage. Induction of severe inflammation, apoptosis, and oxidants/antioxidants imbalance was observed in kidney tissues. DNA damage in the form of 8-hydroxy-2′deoxyguanosine was found. However, pretreatment with Lyc prevented these consequences of arsenic poisoning in the kidneys. We suggest that Lyc exerts its nephroprotective effect via the Nrf2/HO-1 pathway, making it a promising prophylactic agent against arsenic toxicity. [ABSTRACT FROM AUTHOR]

Sodium arsenite is a dangerous bio-accumulative poison affecting a large number of people as well as animals throughout the world. It is used clinically in the treatment of certain medical conditions, but due to its harmful damage to different tissues and mainly the cardiotoxicity, its medical application is limited. This study was conducted to investigate the protective effects of spirulina on cardiotoxicity induced by sodium arsenite biochemically and histologically. 30 young adult male albino rats were randomly equally divided into three groups 10 animals each. Group I (control), Group II Arsenic intoxicated (10 mg/kg/day/ 4 weeks), Group III spirulina protected animals (concomitant sodium arsenite 10 mg/kg/day/ 4 weeks and spirulina 200 mg/kg/day/ 4 weeks). It was evident from the study that arsenic exposure exerted a significant increase in cardiac enzyme levels, serum creatine kinase MB (CKMB) and troponin. Concomitant treatment with spirulina is considerably recovered their serum levels. Histological alterations associated with arsenite treated animals are significantly decreased after using spirulina. The results of the present study showed that use of spirulina could alleviate the toxic effects on the heart following exposure to arsenic toxicity. [ABSTRACT FROM AUTHOR]

Chronic exposure to toxic inorganic arsenic results in the adverse health effects including skin lesions, cardiovascular diseases, diabetes, neurological disorders, and liver and kidney diseases. Gallic acid (GA) is an important phenolic compound, which could protect different tissues from oxidative stress induced damage. The present study investigated effects of GA against sodium arsenite (SA)-induced renal and hepatic toxicity. Thirty-five rats were randomly divided in to five groups; group 1 was treated with normal saline (2 ml/kg/day, p.o.; for 21 days); group 2 was exposed to SA (10 mg/kg/day, p.o.; for 14 days); groups 3 and 4 were treated with GA (10 and 30 mg/kg/day, respectively; for 7 days) prior to exposure to SA, and treatment was continued up to 21 days in parallel with SA administration; group 5 was treated with GA (30 mg/kg/day, p.o.; for 21 days). The level of MDA, IL-1β, NO and glutathione (GSH) and the activity of glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) were evaluated in kidney and liver tissues. Histopathological parameters and serum levels of ALT, AST, ALP, Cr and BUN were also assessed. Treatment with GA remarkably improved SA-induced alteration of hematological and histopathological parameters; these protective effects were associated with the reduction of SA-induced elevation of MDA, IL-1β and NO levels as well as reduction of GSH level and GPx, SOD and CAT activity. Our results suggest that GA may inhibit SA-induced kidney and liver toxicity through scavenging reactive free radicals and increasing intracellular antioxidant capacity. [ABSTRACT FROM AUTHOR]

Arsenic is commonly found in the natural environment and is toxic agent for living organism in many countries in the world. Studies on animal models suggest that exposure to arsenic may cause reproductive toxicity; however, effect of arsenic on reproductive toxicity has still not been clearly described. This study was focused on cytotoxicity, oxidative stress, and the antioxidant defense system induced with exposure to sodium arsenite in Mus musculus Leydig and Sertoli cells. The cells were exposed to two different concentrations of sodium arsenite of 50 ppb (0.4 μM) and 1000 ppb (7.7 μM) for 24, 48, and 72 h. Following the exposure time, cell viability, cell proliferation, and lactate dehydrogenase (LDH) activity were determining using colorimetric method. Also, we evaluated oxidative stress markers such as glutathione (GSH), lipid peroxidation, hydroxyl radical, hydrogen peroxide levels, and cellular enzymatic antioxidants such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione-s-transferase, and γ-glutamyl transpeptidase (γ-GT). As a result, sodium arsenite exposure in Leydig and Sertoli cells caused cellular cytotoxicity and downregulated the antioxidant defense system by inducing oxidative stress depending on concentration and time. Furthermore, this study demonstrated that when compared with Sertoli cells, Leydig cells were more affected by arsenite toxicity. [ABSTRACT FROM AUTHOR]

Long-term exposure to sodium arsenite was found to induce malignant transformation in human bronchial epithelial (HBE) cell line as evidenced by elevated ROS levels. Although chronic sodium arsenite-induced HBE cell line transformation was associated with elevated ROS generation, it was of interest to determine whether acute sodium arsenite exposure also initiated pulmonary damage. Thus, the aim of this study was to investigate oxidative-stress-related pulmonary damage using a human bronchial epithelial (HBE) cell line. Incubation of ρ+-HBE (in the presence of mitochondrial DNA) cells with various concentrations of sodium arsenite, significantly increased ROS and MDA levels accompanied by decreased SOD activity in a concentration-dependent manner. In contrast, treatment of ρ–HBE (without mitochondrial DNA) cells various concentrations of sodium arsenite a reduction in ROS and MDA levels were noted. However, the SOD activity remained decreased in ρ–HBE cells. This was accompanied by a significant rise in HO-1 protein expressions levels in both cell types with greater changes ρ–HBE cells at the lower sodium arsenite concentrations. Data indicate that acute sodium arsenite exposure exerted a greater effect ρ–HBE cells suggesting that absence of mitochondrial DNA appears to enhance sensitivity to the oxidant actions of inorganic As. [ABSTRACT FROM AUTHOR]

Arsenic-contaminated drinking water and its association to different diseases has been considered a severe problem worldwide. The goal of the present study was to evaluate the histopathological changes in oviduct of female rat following 4-week exposure to different doses (50, 100, and 200 ppm) of sodium arsenite. Treatment was initiated when rat reaches the age of 4 weeks. Body weight of animals was recorded weekly. Weight, diameter, and arsenic deposition in oviduct were estimated. Based on anatomical division of oviduct, histology of isthmus and ampulla was examined for any histopathological changes. A dose-dependent decrease was observed in body weight and oviduct weight of treated rats as compared to untreated control rat and low-dose group. Higher arsenic deposition was found in oviduct with the increased doses of arsenite. Cellular arrangement was found disorganized and loosely packed in the epithelium and muscle layers of all treated groups, but was more conspicuous at 200 ppm dosage. Fewer cilia were seen in isthmus and ampulla of treated groups, and almost no cilia were observed in isthmus of 200 ppm group. Muscle layer thickness and epithelium height of arsenic treated rats was reduced in a dose-dependent manner from low (50 ppm) to high group (200 ppm) as compared to control rats. This study found that arsenite treatment adversely affected the body weight of female rats and induced histopathological changes in the cellular structure, configuration, and organization of oviduct in female rats. [ABSTRACT FROM AUTHOR]

This study showed the relevance of using chromosomal aberration (CA) as potential indicators of sodium arsenite (SA; NaAsO2) cytotoxicity. The study investigated cytotoxic potential of SA in Oreochromis niloticus using CA assessment. The fish were exposed to four different concentrations of SA (5, 10, 20 and 40 mg/L) for 24 hours in comparison to a control group. The As concentrations in the samples were analysed by inductively coupled plasma atomic emission spectrometry. The differences in As concentrations in the water and O. niloticus samples between the control and experimental groups were significant (p<0.05), whereas the within experimental group differences were not significant. The cytotoxic assessment of SA in O. niloticus revealed five types of CAs, including single chromatid gaps (SCG), single chromatid break (SCB), centric gap (CG), fragmentation (F) and deletion (D). The most common CA in the O. niloticus samples was SCG. A total of 2.33, 10.67, 18.67, 18.00 and 23.67% of the cells in the control and experimental groups exhibited CAs. The numbers of CAs and cells with CAs from the control and experimental groups of fish were significantly different (p<0.05); additionally, the fish exposed to 5 and 40 mg/L showed significant within experimental group differences (p<0.05). [ABSTRACT FROM AUTHOR]

Sodium arsenite (NaAsO2) is one of the major environmental toxicants with severe toxicological consequences in some developing and developed countries. Rats in Group A received normal saline. Genotoxicity and apoptosis were induced by single intraperitoneal injection of 10 mg/kg sodium arsenite to rats in Groups B–F. Rats in Groups C and D had earlier been pretreated with Azadirachta indica (100 and 200 mg/kg) or E and F with vitamin E (50 and 100 mg/kg), respectively. Markers of oxidative stress, inflammation, hepatic damage, genotoxicity, and apoptosis were assessed. Pretreatment of rats with either Azadirachta indica or vitamin E led to a significant (p <.05) increase in the activities of glutathione-S-transferase (GST), catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH) in the liver compared to the group that received NaAsO2 alone. Markers of oxidative stress and inflammation, malondialdehyde (MDA), hydrogen peroxide (H2O2) generation, nitric oxide (NO), and myeloperoxidase (MPO), were significantly (p <.05) lowered in rats pretreated with Azadirachta indica or vitamin E. The frequency of micronucleated polychromatic erythrocytes (MNPCEs) and expression of caspase-3 were significantly (p <.05) reduced in rats pretreated with either Azadirachta indica or vitamin E compared to rats intoxicated with arsenite. Histopathology of the liver showed areas of infiltration of inflammatory cells with deaths of numerous hepatocytes in NaAsO2-intoxicated rats, and these were reversed by Azadirachta indica. Together, we report for the first time the genoprotective and antiapoptotic effect of Azadirachta indica by a significant reduction in the frequency of micronuclei-induced apoptosis and oxidative stress by arsenic intoxication. [ABSTRACT FROM AUTHOR]

Objectives:Arsenic is a ubiquitous element that is widely distributed in the environment to which man and animals are exposed. Cardiovascular disease is one of the aftermaths of chronic arsenic exposure-related morbidity and mortality. This study sought to investigate the possibility of reversal from arsenic-induced cardio-renal toxicity following exposure and subsequent withdrawal. The study also seeks to understand the mechanism of action of this reversal. Methods:Rats were orally exposed to sodium arsenite at 10, 20 and 40 mg/kg daily for 4 weeks followed by 4 weeks of withdrawal. Results:Exposure to arsenic caused a significant increase in malondialdehyde, H2O2generation but decrease total thiol and reduced glutathione levels in both cardiac and renal tissues. Furthermore, increases in superoxide dismutase, glutathione-S-transferase and catalase with significant increases in glutathione peroxidase activities were observed in the cardiac tissues. On the contrary, a significant reduction in the renal antioxidant enzyme activity was recorded following exposure. Also, antioxidant defense system did not return to apparent values after arsenic withdrawal. Immunohistochemistry revealed a reduction in the expression of the pro-survival protein–protein kinase B (Akt/PKB) following exposure to arsenic and this was not reversed by withdrawal Discussion:Exposure to arsenic caused cardio-renal toxicity via induction of oxidative stress and down-regulation of Akt/PKB expressions. [ABSTRACT FROM AUTHOR]

The present study assessed the cytotoxicity of sodium meta-arsenite (SMA) on telomere shortening and cellular apoptosis in human A-549, MDA-MB-231 and U87-MG cancer cell lines. Following 2 weeks of 1 μM SMA treatment, population doubling time (PDT) was significantly (P < .05) increased by the inhibition of cell proliferation in all the cancer cell lines compared to that in untreated controls. Level of telomerase activity by relative-quantitative telomerase repeat amplification protocol was significantly (P < .05) downregulated by SMA treatment with significant (P < .05) decrease of both telomerase reverse transcriptase and telomerase RNA component transcripts, responsible for telomerase activity. A significant (P < .05) shortening of telomeric repeats by telomere restriction fragment analysis was consequently observed in SMA-treated cells. Moreover, high incidence of cells with senescence-associated β-glucosidase activity was observed in SMA-treated cells and some cells were also differentiated into adipocytes probably due to the loss of tumorous characterizations. Cellular apoptosis proven by DNA fragmentation was observed, and intrinsic apoptotic transcripts (BAX, caspase 3 and caspase 9) and stress-related transcripts (p21, HSP70 and HSP90) were significantly (P < .05) increased in three cancer cell lines treated with SMA. Based on the present study, SMA treatment apparently induced a shortening of telomere length and cytotoxicity, such as induction of cell senescence, apoptosis and cell differentiation. Therefore, we conclude that SMA treatment at specific concentration can lead to gradual loss of tumorous characterizations and can be considered as a potential anti-cancer drug for chemotherapy treatment. [ABSTRACT FROM AUTHOR]

Garcinia kolaHeckel (Clusiaceae) has been widely used in ethnomedicine practice as a therapy against numerous disorders. Therefore, this study was designed to evaluate the protective effects of orally administeredG. kolastem bark ethanolic extract (EEGK) and triterpenoid fraction (TFGK) against sodium arsenite-induced hepatotoxicity and nephrotoxicity using rat models for 14 days. Assays for plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin, urea, and creatinine, liver, kidney, and plasma superoxide dismutase (SOD), glutathione peroxidase (GPx) and reduced glutathione (GSH) activities were carried out using spectrophotometric methods. Gas chromatography-mass spectrometry analytical method was used to identify the bioactive compounds present in TFGK and EEGK. Hematological parameters were assayed using autoanalyzer. Data showed that TFGK reduced liver function markers viz. ALT, AST, ALP, and total bilirubin, while EEGK reduced kidney function markers viz. plasma creatinine and urea. Furthermore, EEGK elevated plasma, liver and kidney SOD, GPx, and GSH while TFGK modulated hematological markers. Findings from this study showed that TFGK substantially protected against sodium arsenite-induced hepatotoxicity while EEGK protected against sodium arsenite-induced nephrotoxicity. [ABSTRACT FROM PUBLISHER]

Oxidative stress-mediated mitochondrial dysfunction is considered the major mechanism of arsenic-induced neurotoxicity. With the present study, the regulation of the 13 subunits of cytochrome c oxidase in rat brain following arsenic exposure was evaluated. Rats were exposed to sodium arsenite (2.5 mg/kg b.wt., by gavage) for 12 weeks. The mRNA expression of the subunits was analysed using reverse transcription polymerase chain reaction. The mRNA expression of all the mitochondria-encoded subunits and selective nuclear-encoded subunits was downregulated. Analysis of mRNA expression of nuclear respiratory factor-1 and nuclear respiratory factor-2 also showed downregulation. [ABSTRACT FROM PUBLISHER]

Arsenic (As), in the form of trivalent arsenite or pentavalent arsenate, is a ubiquitous toxic compound naturally occurring in the environment. This study aimed to evaluate the impact of two different forms of inorganic As on reproductive parameters following oral exposure. Adult Wistar male rats were exposed to sodium arsenite or arsenate at concentrations of 0.01 mg/L or 10 mg/L for 56 d in drinking water. Sodium arsenite at both concentrations and sodium arsenate at 10 mg/L produced reduction in daily sperm production, in number of spermatids in the testis, and in sperm in the epididymal caput/corpus regions. Changes in epididymal morphometry were variable and region specific. Total and progressive sperm motility and sperm morphology did not differ markedly between controls and animals exposed to As. The body and reproductive organs weights, as well as testosterone concentration, remained unchanged among all groups. In conclusion, As exposure in drinking water over 56 d produced damage in male reproductive functions in adult rats, suggesting that fertility problems might occur. Therefore, additional studies need to be undertaken to investigate potential mechanisms underlying sodium arsenite- and arsenate-induced disturbances in fertility and reproductive performance. [ABSTRACT FROM PUBLISHER]

Context:Pistacia lentiscusL. (Anacardiaceae) is an evergreen shrub widely distributed throughout the Mediterranean region.Pistacia lentiscusoil (PLo) was particularly known in North African traditional medicine. Thus, people of these regions have used it externally to treat sore throats, burns and wounds, as well as they employed it internally for respiratory allergies. PLo is rich in essential fatty acids, vitamin E and polyphenols. As a very active site of metabolism, liver is reported to be susceptible to arsenic (As) intoxication. Objective: The present study evaluates the protective effect of PLo against sodium arsenite-induced hepatic dysfunction and oxidative stress in experimental Wistar rats. Materials and methods: Twenty-eight rats were equally divided into four groups; the first served as a control, the remaining groups were respectively treated with PLo (3.3 mL/kg body weight), sodium arsenite (5.55 mg/kg body weight) and a combination of sodium arsenite and PLo. After 21 consecutive days, cellular functions were evaluated by hematological, biochemical and oxidative stress markers. Results: A significant decrease in the levels of red blood cells, haemoglobin (p ≤ 0.001), hematocrit (p ≤ 0.001), reduced glutathione and metallothionein (p ≤ 0.05) associated with a significant increase of malondialdehyde (p ≤ 0.001) were noticed in the arsenic-exposed group when compared to the control. The As-treated group also exhibited an increase in hepatic antioxidant enzymes namely superoxide dismutase, glutathione peroxidase (p ≤ 0.01) and catalase (p ≤ 0.05). However, the co-administration of PLo has relatively reduced arsenic effect. Conclusion: The results showed that arsenic intoxication disturbed the liver pro-oxidant/antioxidant status. PLo co-administration mitigates arsenic-induced oxidative damage in rat. [ABSTRACT FROM PUBLISHER]

The present study was performed to investigate the subchronic effect of sodium arsenite on female Wistar rats. Mature female rats were divided into 4 groups of 12 animals each. Group I received distilled water, whereas the other 3 groups received sodium arsenite at 10, 30, and 50 µg/L doses for 60 days through drinking water. Half of the animals from each group were dissected after 30 days and the remaining after 60 days. A disruption in estrous cycle was observed with prolonged diestrous and metestrous phases. A significant increase in ovarian surface epithelium and follicular atresia was observed in treated rats (p≤ .05). A significant decrease (p≤ .05) in the uterine myometrium was observed. A significant increase (p≤ .05) in the levels of lipid peroxidation along with decrease in the activities of antioxidant enzymes was observed. The results revealed that subchronic exposure of sodium arsenite causes degenerative changes in reproductive organs and induces oxidative stress in female rats. [ABSTRACT FROM AUTHOR]

Chronic exposure of a naturally occurring metal arsenic leads to renal and hepatic diseases. Naringin, a flavanone glycoside, possesses anti-inflammatory and anti-oxidant potential. The aim of this investigation was to evaluate the protective effect of naringin against arsenic-induced renal and hepatic toxicity in rats. Renal and hepatic toxicity was induced in rats by sodium arsenite (5 mg/kg, p.o.). Rats were treated orally with either vehicle or naringin (20, 40, and 80 mg/kg) or Coenzyme Q10 (10 mg/kg) for 28 days. Various biochemical, histological, and molecular biomarkers were assessed in kidney and liver. Treatment with naringin (40 and 80 mg/kg) significantly and dose-dependently restored (p < 0.01 andp < 0.001) altered levels of kidney (serum creatinine, urine creatinine, BUN, uric acid, and creatinine clearance) and liver function test (AST and ALT) induced by sodium arsenite. Elevated levels of oxido-nitrosative stress in renal and hepatic tissue was significantly and dose-dependently decreased (p < 0.01 andp < 0.001) by naringin (40 and 80 mg/kg) treatment. It significantly and dose-dependently down-regulated (p < 0.01 andp < 0.001) renal KIM-1, Caspase-3, TGF-β, and TNF-α mRNA expression. Histopathological alteration induced in kidney and liver by sodium arsenite was reduced by naringin (40 and 80 mg/kg) treatment. In conclusion, naringin treatment ameliorates arsenic-induced renal and hepatic damage in rats due its antioxidant and anti-inflammatory properties via down-regulation of elevated oxido-nitrosative stress, KIM-1, Caspase-3, TGF-β, and TNF-α levels. [ABSTRACT FROM AUTHOR]

Effect ofAcaciahoney from north-west Nigeria on sodium arsenite-induced oxidative damage and clastogenicity in male Wistar rats was investigated. Animals were divided into four groups and were treated daily via oral gavage for one week before they were sacrificed. Brain, liver and blood serum were collected for antioxidant and protein assays. Clastogenicity,in vitroantioxidant activity, vitamins and minerals were also evaluated. From the results, co-administration ofAcaciahoney with sodium arsenite on the animals increased (P < 0.05) glutathione peroxidase, superoxide dismutase and catalase activities with concomitant decrease in malondialdehyde levels and anti-clastogenic effects relative to the group treated with sodium arsenite only. The honey possesses reducing power, high hydrogen peroxide scavenging activity, good amount of vitamins (A, C and E), flavonoids (5.08 ± 0.92 mg QE/100 g) and phenolics (5.40 ± 0.69 mg GAE/100 g). The minerals present include zinc, iron, sodium, magnesium, potassium and calcium. In conclusion,Acaciahoney from Nigeria may mitigate oxidative stress and clastogenicity. [ABSTRACT FROM PUBLISHER]

Arsenic is an environmental contaminant and potential carcinogen. Toxicological assessment of As, which causes hematological alterations and chromosomal aberrations, was studied in freshwater fishOreochromis mossambicus. Fish were exposed to 3 ppm, 28 ppm, and 56 ppm concentrations of sodium arsenite (NaAsO2) and blood samples were collected after 48 h, 96 h, and 192 h of exposure. Hematological assay of exposed fish revealed abnormal mature and immature erythrocytes, deformed erythrocytes (spindle-shaped and triangular erythrocytes) and erythrocytes with segmented nuclei in all treatments. Arsenic exposure induced chromosomal aberration in a concentration-dependent manner, whereas, a decreasing trend was found after 192 h exposure. Observations on blood cells of exposed fish revealed chromosome breaks, chromatid breaks, and chromatid gaps. The alterations and aberrations of these parameters can be effectively used to assess toxicological effects of As on fish in the aquatic environment and at the same time this study elucidates the potential risks to humans who live in arsenic-contaminated areas. [ABSTRACT FROM AUTHOR]

The present study investigated the alleviative effect of aqueous extract of Trichosanthes dioica fruit (AQTD) against arsenic induced cardiotoxicity in Wistar albino rats. AQTD (50 and 100 mg/kg) was administered orally to rats for 20 consecutive days before oral administration of sodium arsenite (10 mg/kg) for 8 days. Then the body weights, heart weights, hematological profile, serum biochemical profile; myocardial antioxidative parameters viz. lipid peroxidation, reduced and oxidized glutathione, glutathione- S-transferase, glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), and DNA fragmentation were evaluated. Pretreatment with AQTD markedly and significantly normalized body weights, heart weights, hematological profile, serum biochemical profile and significantly modulated all the myocardial antioxidative parameters and reduced DNA fragmentation in arsenic intoxicated rats. Therefore, T. dioica fruit possessed remarkable alleviative effects against arsenic induced myocardial toxicity in Wistar albino rats mediated by amelioration of arsenic induced myocardial oxidative stress by several mechanisms. [ABSTRACT FROM AUTHOR]

Hu antigen R (HuR) regulates stress responses through stabilizing and/or facilitating the translation of target mRNAs. The human TRA2β gene encodes splicing factor transformer 2β (Tra2β) and generates 5 mRNA isoforms (TRA2β1 to -5) through alternative splicing. Exposure of HCT116 colon cancer cells to sodium arsenite stimulated checkpoint kinase 2 (Chk2)- and mitogen-activated protein kinase p38 (p38MAPK)-mediated phosphorylation of HuR at positions S88 and T118. This induced an association between HuR and the 39-nucleotide (nt) proximal region of TRA2β exon 2, generating a TRA2β4 mRNA that includes exon 2, which has multiple premature stop codons. HuR knockdown or Chk2/p38MAPK double knockdown inhibited the arsenite-stimulated production of TRA2β4 and increased Tra2β protein, facilitating Tra2β-dependent inclusion of exons in target pre-mRNAs. The effects of HuR knockdown or Chk2/p38MAPK double knockdown were also confirmed using a TRA2β minigene spanning exons 1 to 4, and the effects disappeared when the 39-nt region was deleted from the minigene. In endogenous HuR knockdown cells, the overexpression of a HuR mutant that could not be phosphorylated (with changes of serine to alanine at position 88 [S88A], S100A, and T118A) blocked the associated TRA2β4 interaction and TRA2β4 generation, while the overexpression of a phosphomimetic HuR (with mutations S88D, S100D, and T118D) restored the TRA2β4-related activities. Our findings revealed the potential role of nuclear HuR in the regulation of alternative splicing programs under oxidative stress. [ABSTRACT FROM AUTHOR]

A mouse assay for measuring the relative bioavailability (RBA) of arsenic (As) in soil was developed. In this study, results are presented of RBA assays of 16 soils, including multiple assays of the same soils, which provide a quantitative assessment of reproducibility of mouse assay results, as well as a comparison of results from the mouse assay with results from a swine and monkey assay applied to the same test soils. The mouse assay is highly reproducible; three repeated assays on the same soils yielded RBA estimates that ranged from 1 to 3% of the group mean. The mouse, monkey, and swine models yielded similar results for some, but not all, test materials. RBA estimates for identical soils (nine test soils and three standard reference materials [SRM]) assayed in mice and swine were significantly correlated (r = 0.70). Swine RBA estimates for 6 of the 12 test materials were higher than those from the mouse assay. RBA estimates for three standard reference materials (SRM) were not statistically different (mouse/swine ratio ranged from 0.86–1). When four test soils from the same orchard were assessed in the mouse, monkey, and swine assays, the mean soil As RBA were not statistically different. Mouse and swine models predicted similar steady state urinary excretion fractions (UEF) for As of 62 and 74%, respectively, during repeated ingestion doses of sodium arsenate, the water-soluble As form used as the reference in the calculation of RBA. In the mouse assay, the UEF for water soluble AsV(sodium arsenate) and AsIII(sodium [meta] arsenite) were 62% and 66%, respectively, suggesting similar absolute bioavailabilities for the two As species. The mouse assay can serve as a highly cost-effective alternative or supplement to monkey and swine assays for improving As risk assessments by providing site-specific assessments of RBA of As in soils. [ABSTRACT FROM PUBLISHER]

Arsenic is a significant environmental concern worldwide, primarily due to geo physiochemical contamination of drinking water, and a major public health hazard in both developing and developed countries. The present study was aimed to investigate ameliorative effects of curcumin (Cur) against sodium arsenite (SA)-induced toxicity in cultured murine Sertoli cells. The cells were treated with SA (5 μM) and Cur (5 μg/ml and 10 μg/ml) alone or in combination for 12 hr. The SA treatment decreased cell viability, produced oxidative stress, and induced apoptosis as reflected by reactive oxygen species (ROS) generation, loss of mitochondrial transmembrane potential, DNA fragmentation, and apoptotic cells. Moreover, the SA-induced cell cycle arrest in the cells is characterized by a rise in the number of cells in the sub G1 phase of the cell cycle. The Cur was found to be effective in reversing all these arsenic (As)-induced cellular events. Data suggest that Cur modulates As-mediated oxidative stress, apoptosis, DNA fragmentation, and cell cycle arrest through suppression of excessive ROS generation. Evidence indicates that Cur may emerge as a useful protective agent against As-induced Sertoli cells toxicity by inhibiting As-induced damage in testes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Context: Arsenic, a toxic metalloid with major health concerns, elicits upregulation of heat shock protein 70 (HSP70) in rat hepatoma FGC4 cells, together with evidence of detachment of viable cells from the growth substratum. Objective: To determine if this cell detachment was linked to anoikis, and the impact of this on measurement of HSP70 expression. Materials and methods: FGC4 cells were exposed to sodium arsenite, and detached and attached cells were taken for assessment of cell viability, activation of procaspase-3, and expression of HSP70. Results: Exposure to sodium arsenite led to loss of viable cells from the substratum, associated with apoptosis in detached, but not attached, cells. Upregulation of HSP70 of a similar magnitude was demonstrated in both cell populations. Exposure of cells to cadmium chloride, a toxic metal, also of major environmental concern and believed to act by an oxidative stress mechanism, produced very little release of viable cells from the culture substratum, was not associated with apoptosis, but did elicit a modest upregulation of HSP70 in both cell populations. Discussion: Exposure of FGC4 cells to sodium arsenite elicits anoikis, a form of anchorage-dependent apoptosis, and assessment of the level of HSP70 upregulation in such cells should take account of the detached cell population. Further, the data suggest that this phenomenon is selective to sodium arsenite, rather than to another toxic element that shares a similar mechanism of toxicity. [ABSTRACT FROM AUTHOR]

Arsenic is a potent environmental pollutant and immunotoxic agent. Curcumin is a natural anti-oxidant used to treat a broad variety of diseases. Here, the effects were investigated of curcumin on sodium arsenite-induced apoptosis in murine splenocytes in vitro. Cells were exposed to sodium arsenite (NaAsO2, 5 µM) with and without curcumin (5 and 10 µg/ml) and incubated at 37°C for 12 h. NaAsO2 caused a decrease in cell viability and induction of apoptosis. These outcomes were concurrent with increases in the numbers of cells with reactive oxygen species generation, loss of mitochondrial transmembrane potential, an increase in the frequency of cells with sub-G1 DNA content, and DNA fragmentation. Co-administration of curcumin with the NaAsO2 caused significant recoveries in cell viability values and mitigation of the induced apoptosis-related molecular changes. A significant protection against apoptosis parameters in murine splenocytes simultaneously treated with NaAsO2 and curcumin suggested a protective efficacy of curcumin. From the results it is concluded that the immuno-modulation exerted by curcumin might be attributed to its multifaceted effects including its anti-oxidative and anti-apoptotic properties. These findings have implications not only for the under-standing of the toxicity of arsenic to murine splenocytes in vitro but are also potentially important for developing preventive and/or corrective strategies against/during chronic arsenicosis. [ABSTRACT FROM AUTHOR]

This study evaluated the ameliorative potential of hydroalcoholic extract of Trichosanthes dioica root (TDA) against arsenic (As)-induced toxicity in rat brain. TDA (5 and 10 mg kg−1) was administered orally to Wistar albino rats for 20 consecutive days before oral administration of sodium arsenite (10 mg kg−1) for 8 days. Brain biochemical parameters including lipid peroxidation, reduced and oxidized glutathione, glutathione-S-transferase, glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase, and DNA fragmentation were determined. Pretreatment with TDA significantly and dose-dependently modulated all the antioxidative parameters and reduced DNA fragmentation in As-exposed rat brain. Data indicate that T. dioica root produced remarkable ameliorative effects against As-induced brain toxicity in rats mediated by modulation of oxidative stress. [ABSTRACT FROM PUBLISHER]

The toxicity of sublethal concentration (1 mg/L; 5% of 96hLC50 value) of sodium arsenite (NaAsO2) for 60 days on certain biomolecules (proteins, lipids, and water) of five vital organ systems (muscles, liver, brain, skin, and gills) of Clarias batrachus were analyzed to evaluate the damage rendered to the food value of the fish. Arsenic disturbs the equilibrium existing between these nutritionally important macromolecules in all the organ systems. These tissues showed marked fluctuations in their protein (1.56 ± 0.79% in gills to 4.46 ± 1.54% in muscles), lipid (1.79 ± 0.89% in skins to 4.81 ± 1.15% in brain tissue) and water contents (65.84 ± 1.01% in brain to 78.66 ± 0.37% in gills). [ABSTRACT FROM PUBLISHER]

The present work focussed on the effect of exogenous αα-lipoic acid (ALA) administration on retention memory and oxidative stress markers in the hippocampus subsequent to early post-natal exposure of rat pups to sodium arsenite (NaAsO2). Wistar rat pups were divided into the control groups receiving either no treatment (Ia) or distilled water by intraperitoneal route (i.p.) (Ib) and the experimental groups receiving either NaAsO2 alone (1.5 and 2.0 mg/kg body wt.) (IIa, IIb) or NaAsO2 (1.5 and 2.0 mg/kg body wt.) followed by ALA (70 mg/kg body wt.) (IIIa, IIIb) (i.p.) from post-natal day (PND) 4--15. The initial and retention transfer latency (ITL and RTL) was determined on PND 14 and 15 using elevated plus maze. The animals were sacrificed by cervical decapitation (PND 16) and the brains were obtained. The dissected out hippocampus was processed for estimation of oxidative stress markers, glutathione (GSH), and superoxide dismutase (SOD). NaAsO2 exposure resulted in longer RTL in animal groups IIa and IIb, thereby suggestive of arsenic-induced impairment in retention memory. RTL was significantly shorter in animal groups (IIIa, IIIb) receiving ALA following NaAsO2, thereby suggestive of improvement in retention memory. GSH and SOD levels were significantly decreased in animals receiving NaAsO2 alone as against group Ib and administration of ALA following NaAsO2 increased the levels of hippocampal GSH and SOD. These observations are suggestive of the role of exogenous ALA in ameliorating the adverse effects induced by NaAsO2 exposure of rat pups on retention memory and oxidative stress markers. [ABSTRACT FROM AUTHOR]

The effects of sodium arsenite exposure from postnatal day (PND) 1 to PND 14 on Leydig cells of Wistar rat testes were investigated at PND 15 and 21. Gross morphometric observations of testes did not reveal a significant change in the numerical density and volume of the testes in exposed animals compared to controls either at PND 15 or 21. However, there was significant decrease in testicular weight at PND 21 in treated animals. Measurement of nuclear area of Leydig cells revealed a decrease in nuclear area of these cells in exposed groups at PND 15 and 21. A significant decrease in the total number of Leydig cells was apparent at PND 21 in the treated group. The observations of the present study are indicative of adverse effects on rat testes Leydig cells following exposure to low doses of sodium arsenite during critical window periods. The persistence of these observations at PND 21 is suggestive of irreversible damage to testicular tissue. [ABSTRACT FROM AUTHOR]

The natural habitats of the freshwater bivalve Lamellidens marginalis face the risk of contamination by the toxic metalloid arsenic. Haemocyte-mediated non-self phagocytosis and generation of nitric oxide (NO) as reactive nitrogen intermediate were examined to establish the reliability of the parameters as biomarkers of sodium arsenite-induced stress on the animal at sublethal concentrations. The studies suggest imposition of a remarkable immune compromise/immune suppression on the animal by the natural contaminant. The animal expressed partial recovery in its phagocytic potential and NO generation over a period of 30 days. Quantitation of phagocytic efficiency and intrahaemocyte NO generation indicates the possibility of the parameters be accepted as cellular biomarkers to estimate and characterize the vulnerability of the freshwater organisms to sodium arsenite-induced stress. [ABSTRACT FROM AUTHOR]

o-Phenylenediamine has been used as a reagent to quantify nitrites/nitrates in a variety of sample matrices. The method is based on the cyclization reaction between o-phenylenediamine and nitrite in acid medium. The amine undergoes diazotization with nitrite in the presence of acid to form the diazonium ion, which subsequently cyclizes to yield yellowish orange benzotriazole at room temperature with an absorption maximum at 450 nm. The formed dye has been separated, purified, and characterized by IR, NMR, and spectroscopy techniques. The parameters of the reaction between amine and nitrite have been optimized. The effect of interfering ions on the determination of nitrites/nitrates has been described. The developed method has been applied for the determination of residual NO2 gas present in the ambient air after fixing it as a nitrite ion using sodium arsenite as a trapping medium. The dye formed has been extracted into organic solvent to improve the detection limit during the measurement of low levels of ambient NO2 in air. The method obeyed Beer's law in the concentration range 0-250 µg in aqueous medium and 0-50 µg in organic medium with molar absorptivity of 4.09 × 104 L mol-1 cm-1 and 4.3 × 104 L mol-1 cm-1 respectively. Nitrate is determined by reducing it to nitrite after passing through the copperized cadmium reductor column. The developed method has been applied to determine nitrite/nitrate levels in water, soil, and biological samples. [ABSTRACT FROM AUTHOR]

A simple and sensitive spectrophotometric method for the determination of nitrogen dioxide in ambient air and nitrite/nitrate in water and soil samples has been developed. Nitrogen dioxide in air has been fixed as nitrite ion using alkaline sodium arsenite as absorbing medium. The method is based on the reaction of nitrite with aminophenyl benzimidazole in acid medium to form diazonium ion, which is coupled with N-(1-naphthyl)ethylenediamine dihydrochloride to form an azo dye with an absorption maximum at 555 nm in aqueous phase. The method obeys Beer's law in the concentration range 0-10 µg of nitrite in 25 ml solution. The molar absorptivity has been found to be 6.3×104 l mol-1 cm-1. The dye can be extracted quantitatively into isoamyl alcohol under alkaline condition and the addition of methanolic hydrochloric acid restores the original dye colour. Beer's law is obeyed in the concentration range 0-2 µg of nitrite with a detection limit of 0.009 µg. The effect of interfering species has been studied and the developed method has been applied to determine trace levels of nitrogen dioxide in ambient air and the results have been compared with the standard method. It is also applied to measure the nitrite/nitrate levels of surface and ground water samples collected from lakes, tube wells as well as soil samples. [ABSTRACT FROM AUTHOR]

Arsenic trioxide (As 2 O 3 ) induces remission in patients with acute promyelocytic leukemia (APL). To better understand molecular mechanisms of arsenic actions, this study investigated the effect of two different arsenic compounds on gene expression of apoptosis and cellular proliferation related genes. The Wilms' tumor gene (wt1) is up-regulated in acute myeloid leukemia (AML) and a variety of leukemia cell lines. The expression of wt1 in these cells is proposed to have an anti-apoptotic effect. HL-60 and K562 were treated with arsenic trioxide (As 2 O 3 ) and sodium arsenite (NaAsO 2 ) at concentrations between 0 – 10 μm for up to 48 h. The induction of apoptosis was accompanied by down-regulation of hTERT and wt1 mRNA and protein expression but up-regulation of par-4. Low concentrations of 0.1 μm arsenic induced expression of the anti-apoptotic bcl-2 gene in both cell lines HL-60 and K562. There were no major differences encountered between compounds. After arsenic treatment of the leukemia cell lines HL-60 and K562 the up-regulation of par-4 may contribute to the induction of apoptosis rather than down-regulation of bcl-2. The therapeutic effect of arsenic is the induction of apoptosis by modulating the gene expression profile of pro- and anti-apoptotic genes including the wt1 gene. [ABSTRACT FROM AUTHOR]