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From the in vitro level, this paper explores the synergistic inhibitory effects and mechanisms of sodium arsenite (NaAsO2) and astragaloside IV(AS-IV) on HepG2 cells. By screening the optimal concentration of each drug, the authors tested the combined and separate effects of the two drugs on HepG2 cell proliferation, migration and invasion, cell cycle and apoptosis, as well as key genes and proteins of the PI3K/AKT/mTOR pathway (PI3K, p-PI3K, AKT, p-AKT, mTOR, and p-mTOR). The CCK-8 test and Transwell tests show that: the separate and joint uses of NaAsO2 and AS-IV reduced the viability and migration of cells to different degrees (p all NaAsO2 group > AS-IV group; GNGT1 siRNA group had an opposite trend with each treatment group. From in vitro level, the above results confirm that NaAsO2 and AS-IV can inhibit HepG2, and the two drugs has a synergistic effect. In addition, the two drugs could inhibit HepG2 cells through the PI3K/AKT/mTOR signaling pathway; GNGT1 participates in the regulation of that signaling pathway.

There is solid epidemiological evidence that arsenic exposure leads to cognitive impairment, while experimental work supports the hypothesis that it also contributes to neurodegeneration. Energy deficit, oxidative stress, demyelination, and defective neurotransmission are demonstrated arsenic effects, but it remains unclear whether synaptic structure is also affected. Employing both a triple-transgenic Alzheimer’s disease model and Wistar rats, the cortical microstructure and synapses were analyzed under chronic arsenic exposure. Male animals were studied at 2 and 4 months of age, after exposure to 3 ppm sodium arsenite in drinking water during gestation, lactation, and postnatal development. Through nuclear magnetic resonance, diffusion-weighted images were acquired and anisotropy (integrity; FA) and apparent diffusion coefficient (dispersion degree; ADC) metrics were derived. Postsynaptic density protein and synaptophysin were analyzed by means of immunoblot and immunohistochemistry, while dendritic spine density and morphology of cortical pyramidal neurons were quantified after Golgi staining. A structural reorganization of the cortex was evidenced through high-ADC and low-FA values in the exposed group. Similar changes in synaptic protein levels in the 2 models suggest a decreased synaptic connectivity at 4 months of age. An abnormal dendritic arborization was observed at 4 months of age, after increased spine density at 2 months. These findings demonstrate alterations of cortical synaptic connectivity and microstructure associated to arsenic exposure appearing in young rodents and adults, and these subtle and non-adaptive plastic changes in dendritic spines and in synaptic markers may further progress to the degeneration observed at older ages.

The prime objective of the present study was to establish fenugreek (Trigonella foenum-graecum L.) seeds extract as an antidote against arsenic induced hepato-renal toxicity in rats. The male Charles Foster rats (weighing 160-180 g) were selected to make arsenic intoxicated model. The arsenic treated group of rats were orally treated with sodium arsenite at the dose of 8 mg/kg body weight/day for 90 days. Thereafter, the arsenic pretreated rats were further administered with fenugreek ethanolic seeds extract at the dose of 250 mg/kg body weight/day for 90 days. After the completion of the treatment, animals of all the groups were sacrificed for the biochemical and histopathological estimation. The arsenic treated rats showed significant (p < 0.0001) alterations at the various hepatic and renal biomarker parameters and at serum MDA levels in comparison to the control rats. Significant (p < 0.0001) arsenic accumulation was also observed in the blood, liver and kidney tissues of the arsenic treated rats. However, after the administration with fenugreek seeds extract, significant (p < 0.0001) restoration was observed in the liver and kidney biomarker parameters and at haematological variables. Fenugreek seeds extract administration also significantly (p < 0.0001) reduced the serum MDA levels and arsenic concentration levels in blood, liver and kidney tissues, along with considerable restorations at the cellular architecture of liver and kidney tissues. The study concluded that fenugreek seeds possessed potential hepato-renal ameliorative effect against sodium arsenite induced toxicity in rats, and can be used for its therapeutic value against arsenic poisoning.

Arsenic and the compounds thereof can be carcinogens or therapeutic agents for different cancer types. However, for breast cancer (BC), studies have yielded conflicted results on the role of arsenic. A previous study by the present authors indicated a potential relationship between circDHX34 and sodium arsenite-treated BC cells. As such, the expression, function, and potential mechanism of circDHX34 in sodium arsenite-treated MDA-MB-231 cells were further detected. In the present study, findings were made that sodium arsenite upregulated circDHX34 expression in MDA-MB-231 cells in a dose-dependent manner, and knockdown of circDHX34 could promote cell proliferation and inhibit apoptosis. Further investigations revealed that knockdown of circDHX34 upregulated the expression levels of antiapoptotic genes BCL2 and BCL2L1 and downregulated the expression levels of proapoptotic genes CASP8 and CASP9. To conclude, by regulating apoptotic genes, sodium arsenite-mediated upregulation of circDHX34 promotes apoptosis in hormone-independent breast cancer cells.

Moringa oleifera (MO) is a plant of significant medicinal importance. The dried leaves of MO were pulverized, extracted with ethanol and fractionated using column chromatography to provide seven fractions (MOF1-7) with MOF6 having the best preliminary antioxidant potential. Therefore, this study evaluated the hepatoprotective potentials of MOF6 in sodium arsenite (SA)-induced hepatotoxicity in rats. Thirty-five adult male Wistar rats were randomly divided into seven groups of five rats each. Control Group I received normal saline. Groups II and III received 20 mg/kg body weight (bw) of SA for 3 and 6 weeks, respectively. Groups IV and V received 20 mg/kg bw of SA for 3 weeks followed by treatment with 5.0 and 7.5 mg/kg bw of fraction MOF6, respectively, for 6 weeks. Groups VI and VII received only 5.0 and 7.5 mg/kg bw of fraction MOF6, respectively, for 6 weeks. Antioxidant (lipid peroxidation) and biochemical analyses of liver enzymes of all rats were carried out after the completion of experimental procedures. Results showed statistically significant lower mean values (p ≤ 0.05) of malondialdehyde (MDA), acid phosphatase (ACP) and γ-glutamyl transferase (GGT) in rats of Groups IV and V compared with Group III. However, there were statistically significant higher mean values (p ≤ 0.05) of alkaline phosphatase (ALP) in Groups IV and V compared with Groups I and III. In conclusion, these results implied that fraction MOF6 has antioxidant and hepatoprotective potentials. However, results of ALP analyses implied that MOF6 possibly augmented SA-induced hepatotoxicity in rats.

Arsenic exposure to the population leads to serious health problems like neurotoxicity, nephrotoxicity, and cardiovascular abnormality. In the present study, the work has been commenced to discover the prospect of rolipram a phosphodiestrase-4 (PDE-4) inhibitor against sodium arsenite (SA)-induced vascular endothelial dysfunction (EnDF) leading to dementia in rats. Wistar rats were treated with SA (5 mg/kg body weight/day orally) for 44 days for induction of vascular EnDF and dementia. Learning and memory were evaluated using Morris water maze (MWM) test. Vascular EnDF was evaluated using aortic ring preparation. Various biochemical parameters were also evaluated like brain oxidative stress (viz. reduced glutathione and thiobarbituric acid reactive substances level), serum nitrite/nitrate activity, acetylcholinesterase activity, and inflammatory markers (viz. neutrophil infiltration in brain and myeloperoxidase). SA-treated rats showed poor performance in water maze trials indicating attenuated memory and ability to learn with significant rise (p < 0.05) in brain acetylcholinesterase activity, brain oxidative stress, neutrophil count, and significant decrease (p < 0.05) in serum nitrite/nitrate levels and vascular endothelial functions. Rolipram (PDE-4 inhibitor) treatment (0.03 mg/kg and 0.06 mg/kg body weight, intraperitoneally daily for 14 days) significantly improved memory and learning abilities, and restored various biochemical parameters and EnDF. It is concluded that PDE-4 modulator may be considered the prospective target for the treatment of SA-induced vascular EnDF and related dementia.

Objective: Natural substances found in dietary sources and medicinal plants have attracted con¬siderable attention in recent years as chemopreventive agents. Spirulina is a blue-green alga that possesses chemopreventive properties. The purpose of this study was to determine the effect of spirulina on rats with inorganic arsenic (As) [sodium arsenite (NaAsO2)]-induced lipid peroxidation. Materials and Methods: 120 rats were randomly assigned to 10 groups and designated T0, T1, T2, T3, T4, T5, T6, T7, T8, and T9. One group was kept as a control (T0) that received no treatment. The seven groups received 3.0 mg of NaAsO2/kg body weight in drinking water and were given spirulina ad libitum. T1 was treated with NaAsO2 but not with spirulina. Two groups of rats (T2 and T3), on the other hand, were treated with spirulina without receiving any As (NaAsO2). T2 received agro-based spirulina (Ab-Sp; grown in 1.5% soybean meal media and harvested on day 12 of seed inoculation) at 2.0 gm/kg feed, whereas T3 received commercially available spirulina (Com-Sp) at 2.0 gm/kg feed. T4, T5, and T6 were concurrently treated with Ab-Sp at 1.0, 1.5, and 2.0 gm/ kg of feed. On the other hand, T7, T8, and T9 induced by NaAsO2 were concurrently treated with Com-Sp at 1.0, 1.5, and 2.0 gm/kg feed. All groups received treatment for 90 days. Results: The efficacy of both spirulina in preventing lipid peroxidation caused by As was deter¬mined quantitatively by measuring the rats serum malondialdehyde (MDA). The results indicated that As supplementation increased serum MDA levels, whereas both types of spirulina signifi¬cantly decreased them. The highest dose of Ab-Sp (2.0 gm/kg feed) was found to be the most effective in preventing lipid peroxidation in rats treated with inorganic As. Conclusion: Ab-Sp could be a natural, cost-effective, and safe measure to mitigate As toxicity. [J Adv Vet Anim Res 2021; 8(2.000): 330-338]

Arsenic contamination among heavy metals in ground water is a health hazard due to its toxicological concern, affecting millions of humans globally. Purpose: To observe and analyze the histomorphological effects of sodium arsenite on cervix of rat. Study Design: Laboratory based experimental study. Methodology: Present study held at department of anatomy, College of Physician and Surgeon Pakistan, Regional Centre Islamabad, in two principal groups, group A (control) and group B (experimental). The animals of B were administered sodium arsenite by oral gavage daily for 14 days while group A were administered only distilled water daily for 14 days. The animals of both groups were sacrificed after day 14th of drug administration. The cervix was processed for paraffin embedding and stained with Haematoxylin and Eosin (H&E). Statistical analysis: Data analyzed by SPSS 22.0v. Student’s t-test was applied to determine the significance. P-value ≤ 0.05 was considered significant. Results: The histological evaluation of experimental group animals showed decrease in cervical canal’s luminal area, hyperplasia of cervical epithelium and decrease thickness of cervical muscles. Conclusion: The nature of histomorphological effects observed in cervix showed that these changes may be due to oxidative stress produced by the formation of free radicals, decrease levels of serum estradiol, progesterone and by the denaturation of proteins. Key Words: Arsenic, Cervix, Free Radicals, Hyperplasia and Oxidative stress.

Ingestion of arsenic, a known contaminant in drinking water causes cancer at multiple tissues and there is no cure. Consumption of arsenic contaminated water has been implicated metalloid-induced carcinogenesis. Research is therefore directed at chemoprevention using medicinal herbs for the management of arsenicosis. In this study hepatoprotective activity of ethanolic extract of Annona muricata (AM) leaves was assessed against sodium arsenite (SA) induced hepatic injury in albino rats. The animals were pre-treated with either 250 or 500mg/kg body weight of rat before exposure to SA. SA was dissolved in distilled water and administered at a dose of 5 mg/kg body weight on the 7th, 14th and 21st day of the experiment. SA was observed to induce a significant increase (p < 0.05) in serum aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase activities (ALP). However, pretreatments of rats with various doses of AM significantly (P

Arsenic exposure causes immense health distress by increasing risk of cardiovascular abnormalities, diabetes mellitus, neurotoxicity, and nephrotoxicity. The present study explored the role of inducible nitric oxide synthase (iNOS) inhibitors against sodium arsenite-induced renal and hepatic dysfunction in rats. Female Sprague Dawley rats were subjected to arsenic toxicity by administering sodium arsenite (5 mg/kg/day, oral) for 4 weeks. The iNOS inhibitors, S-methylisothiourea (10 mg/kg, i.p.) and aminoguanidine (100 mg/kg, i.p.) were given one hour before sodium arsenite administration in rats for 4 weeks. Sodium arsenite led rise in serum creatinine, urea, uric acid, electrolytes (potassium, fractional excretion of sodium), microproteinuria, and decreased creatinine clearance (

The present study aimed primarily to evaluate the effect of sodium arsenite exposure on glucose metabolism includes glycogen accumulation on rat cortical astrocytes. Furthermore, cell death analysis was concurrently done to determine the toxic effect of sodium arsenite on astrocytes. Rat cortical astrocytes derived from the cerebral cortices of neonatal Wistar rats were treated with sodium arsenite for 24 h. Glucose metabolism was evaluated by determining glucose uptake and glycogen accumulation using glucose uptake kit, and periodic acid–Schiff staining and transmission electron microscopy, respectively. Glycogen synthase (GS) and glycogen synthase kinase-3 (GSK3) were detected by Western blotting. The cell death analysis was assessed by propidium iodide staining. Sodium arsenite exposure at 25 μM for 24 h significantly increased glucose uptake and glycogen content in rat cortical astrocytes. Sodium arsenite exposure significantly increased GS expression but decreased a ratio of GS phosphorylation at serine 641 (inactive) to GS, suggesting that there may be an increase in activity of GS. Moreover, sodium arsenite caused an increase in inactive serine phosphorylation of GSK3, a kinase that phosphorylates and inhibits GS. These results suggested that sodium arsenite increased glycogen synthesis through GS activation mediated by inhibition of GSK3. On the other hand, sodium arsenite exposure at 25 μM caused some degree of cellular damage and a slight increase in cell death in rat astrocytes. Sodium arsenite increased glycogen accumulation through GS activation and caused cell death in rat cortical astrocytes. These observations implicate that the enhancement of glycogen in rat astrocytes by sodium arsenite may be related to its toxicity. Hence, alteration of astrocyte glycogen metabolism may play a role in arsenic toxicity in the brain.

Objectives: Water contaminated with arsenic affected millions of people worldwide and arsenic exposure is related to various neurological disorders. Hence, the current study was planned to investigate the neuroprotective activity of diosmin (DSN) against arsenic induced neurotoxicity as an attempt to identify therapeutic intervention to combat arsenicism. Materials and Methods: Sodium arsenite an inducer of neurotoxicity was administered orally (13 mg/kg) and DSN treatment at two selected doses (50 and 100 mg/kg) was done for 21 days. Behavioral and biochemical variations were examined by various parameters. Furthermore, histopathological and immunohistochemistry studies were done with the brain sections. Results: The behavioral studies evidenced that arsenic has suppressed the exploratory behavior and motor coordination in rats and DSN treatment has recovered the behavioral changes to normal. Arsenic administration has also found to induce oxidative stress and DSN co-treatment has ameliorated the oxidative stress markers. Interestingly, depleted levels of neurotransmitters were observed with the arsenic and it was restored back by the DSN treatment. Histopathological alterations like pyknosis of the neuronal cells were identified with arsenic exposure and subsided upon DSN co administration. Immunohistochemical studies have revealed the expression of NOX4 and its gp91phox and P47phox subunits and its suppression by DSN treatment may be the key therapeutic factor of it. Conclusions: Treatment with DSN showed a beneficial effect in protecting against arsenic-induced neurotoxicity by suppressing the toxicity changes and the antioxidant effect of DSN might be attributed to its ability of suppressing NOX4 and its subunits.

This study investigated the effect of ethanol stem bark extract ofIrvingia gabonensis(ESEIG) on sodium arsenite (SA)-induced pro-inflammatory cytokines and hematological perturbations in Wistar rats. Fifty-five Wistar rats weighing 100 g - 179 g were distributed into eleven groups (n=5). Group 1 had feed and water only. Group 2 received 4.1 mg/kg body weight (kgbw) of SA. Groups 3-11 received SA and/or ESEIG. Treatment was done orally for 14 days. Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), interleukin-4 (IL-4) concentrations, hemoglobin (HB) concentration, red blood cell (RBC) count, packed cell volume (PCV), mean cell hemoglobin concentration (MCHC), mean cell hemoglobin (MCH), mean corpuscular volume (MCV), white blood cell (WBC) count and its differentials and platelet (PLT) count were used to investigate the immunological and hematological effects of ESEIG. Exposure to SA produced significant (p ˂ 0.05) increases in hepatic IL-1β, TNF-α, IL-10 and IL-4 concentrations relative to control. Administration of SA also caused significant (p ˂ 0.05) decreases in HB, RBC, PCV, MCHC, MCH, MCV and PLT and significant (p ˂ 0.05) increases in WBC, lymphocytes, monocytes, eosinophils and neutrophils compared with control. Treatment with ESEIG concomitantly and 2 weeks after SA exposure, mitigated the deleterious effect of SA. However, ESEIG alone at various doses caused significant (p ˂ 0.05) increases in some of the assayed parameters, compared with control. These results imply that ESEIG may be protective against SA-induced inflammation and hematological derangements in Wistar rats. Its exclusive administration on chronic basis may also be slightly toxic.&nbsp

The morphology and oxidation state of arsenic in its compounds affects the skin cell toxicity. Accordingly, the present study was conducted to explore the effects of two different arsenic compounds on the proliferation and survival of Liaoning cashmere goat skin fibroblasts. Based on MTT assay results, at 24 h, the proliferation concentration, critical concentration, and half inhibitory concentration (IC50) of sodium arsenite were 0.50, 5.00, and 45.66 μmol/L, respectively. The corresponding values for dimethyl arsenic acid were 0.85, 1.00, and 38.68 mmol/L. Immunofluorescence, transmission electron microscopy, and mitochondria membrane potential (MMP) assays showed that sodium arsenite promotes microtubule polymerization and increases MMP, while cells treated with dimethyl arsenic acid exhibited cytoskeletal collapse and decreased MMP. In the IC50 groups for both arsenic agents, the cytoskeletons collapsed, microtubules were gathered into bundles, and MMP was significantly decreased. Dimethyl arsenic acid had a stronger effect on MMP than sodium arsenite. Flow cytometry revealed a slightly lower occurrence of apoptosis in the sodium arsenite proliferation group, while it was slightly increased in the dimethyl arsenic acid proliferation group. Apoptosis was increased more significantly in the sodium arsenite IC50 group than in the dimethyl arsenic acid IC50 group. These results indicate that the differences in cell proliferation and cytotoxicity induced by inorganic and organic arsenic are related to their effects on cellular structures.

This study evaluated the neuroprotective effects of MOF6 (isolated from Moringa oleifera leaves) and Trimyristin (isolated from Myristica fragrans seeds) on Acetylcholinesterase concentrations in cerebral cortices of rats with Sodium arsenite-induced neurotoxicity. Sixty-five adult male rats (150 g-250 g) were randomly divided into thirteen groups comprising of five rats per group. Groups 1 and 3 received physiological saline and 1 ml/200 g bodyweight of Olive oil respectively for 9 weeks. Group 2 received 20 mg/kg bodyweight of Sodium arsenite (SA) for 6 weeks and left untreated for another 3 weeks. Groups 4-5 received 20 mg/kg bodyweight of SA for 3 weeks followed by treatments with 5.0 and 7.5 mg/kg bodyweight of MOF6 respectively for 6 weeks. Groups 6-7 received 20 mg/kg bodyweight of SA for 3 weeks followed by treatments with 15 and 30 mg/kg bodyweight of Trimyristin respectively for 6 weeks. Groups 8-11 received 5.0 and 7.5 mg/kg bodyweight of MOF6; 15 and 30 mg/kg bodyweight of Trimyristin respectively for 9 weeks. Groups 12-13 received 7.5 mg/kg bodyweight of MOF6 and 30 mg/kg bodyweight of Trimyristin respectively for 6 weeks followed by co-administration of each extract dose with 20 mg/kg bodyweight of SA for another 3 weeks. Histological examination of cerebral cortices and biochemical analyses of Acetylcholinesterase concentrations were carried out in all rats. Computed data were analyzed using Microsoft Excel 2016 with statistical significance at p≤0.05. Histo-pathological evaluations revealed normal histo-architecture of cerebral cortices of all rats. Results showed statistically significant (p≤0.05) increases in Acetylcholinesterase concentrations in rats of Groups 1-10 and 12 compared with Group 2 (2.78±1.76 𝜇mole/min/g). 7.5 mg/kg bodyweight of MOF6 showed the best therapeutic and neuro-regenerative potential against SA-induced neurotoxicity.Conclusions: Our findings implied that MOF6 and Trimyristin reversed downregulation of Acetylcholinesterase concentrations in SA-induced neurotoxicity in rats; and possess neuro-protective and neuro-regenerative potentials.

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 se...

It is of interest to document the effect of Emblica officinalis (E. officinalis) and Zingiber officinalae (Z. officinalae) leaf extract on reactive oxygen species, antioxidant potential changes in arsenic and lead-induced toxicity in male rats. We used 8 groups of adult male Wistar rats with 1 control group for this study. The animals were divided into Group I: Control and Group II: Lead and sodium arsenite induced rats (animals were induced for metal toxicity by the combined administration of arsenic (13.8 mg/kg body weight) and lead (116.4 mg/kg body weight). These doses were administered by gastric intubation during 14 consecutive days using known standard procedures. Arsenic and lead induced rats treated with ethanolic extract of Emblica officinalis (60 mg/kg body weight/day, orally for 45 days) are group III rats.Group IV animals are arsenic and lead induced rats treated orally with ethanolic extracts of E. officinalis (120 mg/kg body weight/day for 45 days). Group V animals are arsenic and lead induced rats treated orally with ethanolic extracts of Z. officinalae (60 mg/kg body weight/day for 45 days). Group VI animals are arsenic and lead induced rats orally treated with ethanolic extracts of Zingiber officinalis (120 mg/kg body weight/day for 45 days). Group VII animals are arsenic and lead induced rats treated orally with ethanolic extracts of E. officinalis and Z. officinalae (60 + 60 mg/kg body weight/day for 45 days). Group VIII animals are arsenic and lead induced rats treated orally with ethanolic extracts of E. officinalis and Z. officinalae (120 + 120 mg/kg body weight/day, orally for 45 days). Normal Control animals were treated orally with ethanolic extracts of E. officinalis (120mg/kg body weight) + Z. officinalae (120mg/kg body weight) for 45 days. The control and experimental animals were then subjected to analysis for oxidative stress markers such as H2O2, *OH, and lipid peroxidation (LPO), antioxidant enzymes in addition to liver and kidney function markers. Results: Arsenic and lead induced rats showed a significant increase in the levels of reactive oxygen species (H2O2, OH* and LPO) with concomitant alterations in the renal and liver tissues. However, enzymic and non-enzymic antioxidant levels were decreased. Nevertheless, an oral effective dose of E. officinalis and Z. officinalae (120 + 120 mg/kg body weight/day increased the antioxidant enzymes and retrieved the altered levels of ROS and LPO that were induced by arsenic and lead. Thus, we show that E. officinalis and Z. officinalae leaf extract exhibits nephroprotective and hepatoprotective role through the restoration of reactive oxygen species and antioxidant enzymes in the kidney and liver tissue of Arsenic and Lead-induced nephrotoxicity and hepatotoxicity in rats. Hence, E. officinalis and Z. officinalae leaf extract are potential therapeutic options for the treatment of metal toxicity-induced kidney and liver diseases.

Summary: Arsenicosis remains a global health concern due to devastating health effects. Clerodendrum volubile and vernonia amygdalina have tremendous bioactivities against oxidative stress-related diseases. The study, therefore, appraised the effects of flavonoids fractions from C. volubile and V. amygdalina (FCV and FVA respectively) against arsenic-induced oxidative stress in rats. Thirty male Wistar rats (120 ± 10 g) were divided into six groups of five each; Control (distilled water), arsenic alone (40 ppm sodium arsenite), arsenic + FCV (100 mg/kg), arsenic + FVA (100 mg/kg), arsenic + FCV and FVA (50 mg/kg each), and arsenic + vitamin C (100 mg/kg). The treatment commenced after four-week long arsenic exposure and lasted another four weeks. Blood, liver and kidneys of the rats were collected after sacrifice following an overnight fast. Arsenic caused significant (p

Rhodococcus erythropolis S43 is an arsenic-tolerant actinobacterium isolated from an arsenic contaminated soil. It has been shown to produce siderophores when exposed to iron-depleting conditions. In this work, strain S43 was shown to have the putative heterobactin production cluster htbABCDEFGHIJ(K). To induce siderophore production, the strain was cultured in iron-depleted medium in presence and absence of sodium arsenite. The metabolites produced by S43 in the colorimetric CAS and As-mCAS assays, respectively, showed iron- and arsenic-binding properties reaching a chelating activity equivalent to 1.6 mM of desferroxamine B in the supernatant of the culture without arsenite. By solid-phase extraction and two subsequent HPLC separations from both cultures, several fractions were obtained, which contained CAS and As-mCAS activity and which were submitted to LC-MS analyses including fragmentation of the major peaks. The mixed-type siderophore heterobactin B occurred in all analyzed fractions, and the mass of the "Carrano heterobactin A" was detected as well. In addition, generation of a molecular network based on fragment spectra revealed the occurrence of several other compounds with heterobactin-like structures, among them a heterobactin B variant with an additional CH2O moiety. 1H NMR analyses obtained for preparations from the first HPLC step showed signals of heterobactin B and of "Carrano heterobactin A" with different relative amounts in all three samples. In summary, our results reveal that in R. erythropolis S43, a pool of heterobactin variants is responsible for the iron- and arsenic-binding activities. KEY POINTS: • Several heterobactin variants are the arsenic-binding compounds in Rhodococcus erythropolis S43. • Heterobactin B and the compound designated heterobactin A by Carrano are of importance. • In addition, other heterobactins with ornithine in the backbone exist, e.g., the new heterobactin C.

Arsenic is a naturally occurring environmental toxicant, chronic exposure to arsenic can cause multiorgan damage, except for typical skin lesions, liver damage is the main problem for health concern in population with arsenic poisoning. Abnormal apoptosis is closely related to liver-related diseases, and p53 is one of the important hallmark proteins in apoptosis progression. This study was to investigate whether arsenic poisoning-induced hepatocyte apoptosis and the underlying role of p53 signaling pathway. A rat model of arsenic poisoning was established by feeding corn powder for 90 days, which was baked with high arsenic coal, then were treated with Ginkgo biloba extract (GBE) for 45 days by gavage. The results showed that arsenic induced liver damage, increased hepatocyte apoptosis and elevated the expression level of Chk1 and the ratios of p-p53/p53 and Bax/Bcl-2 in liver tissues, which were significantly attenuated by GBE. Additionally, to further demonstrate the potential apoptosis-associated mechanism, L-02 cells were pre-incubated with p53 inhibitor pifithrin-α (PFTα), ataxia telangiectasia-mutated (ATM)/ataxia telangiectasia-mutated and Rad3-related (ATR) inhibitor (CGK733) or GBE, then treated with sodium arsenite (NaAsO2) for 24 h. The results showed that GBE, PFTα or CGK733 significantly reduced arsenic-induced Chk1 expression and the ratios of p-p53/p53 and Bax/Bcl-2. In conclusion, Chk1-p53 pathway was involved in arsenic poisoning-induced hepatotoxicity, and inhibiting of Chk1-p53 pathway ameliorated hepatocyte apoptosis caused by coal-burning arsenic poisoning. The study provides a pivotal clue for understanding of the mechanism of arsenic poisoning-induced liver damage, and possible intervention strategies.

Arsenic (As) indelibly exists in the environment and may reach to a food chain. Flavors and herbs are recognized sources of natural antioxidants that play imperative against harmful chemical pollutants. Ginger is utilized around the world as a zesty condiment. This study assessed the ability of ginger extract (GE) as a protector to improve regenerative disabilities initiated by sodium arsenate in reproductive functions in male rats. Thirty-two Sprague-Dawley male rats weighted 240 ± 10 g were arbitrarily relegated into four experimental groups (n = 8): the control group; the GE-treated group received at 100 mg/kg BW; the As-treated group received sodium arsenite at 10 mg/kg BW; the fourth group received sodium arsenite additionally GE at mentioned doses for 4 weeks. Phytochemical results of GE revealed that GE had good antioxidative characteristics and high content of total flavonoid, tannins, alkaloids, and total phenolic components. Simultaneously, treatment of GE showed protection against oxidative stress induced by As and restoration of the serum cholesterol, testosterone, LH, and sperm parameter to normal levels. GE significantly improved the antioxidant activities (GSH, SOD, and CAT) as well as H2O2 and MDA in rats received concurrently the GE and As compared with control group. Moreover, the expression of genes controlling the cholesterol transportation and testosterone synthesis (SR-B1, StAR, CYP11A1, 3b-HSD, 17b-HSD, and CYP17a) as well as LHR showed a meaningful improvement in rats treated by GE plus As compared with their expression in the As-treated group. Besides, GE treatment exhibited significant recovered testis histopathological alterations, reduced the arsenic content in testes, and improved the sperm parameters.

Graphical abstract, Highlights • Uranium and arsenic co-occur as contaminants in water sources in the Southwestern US. • Exposure to metals may alter gene expression and cause immune dysregulation in CD4+ T-cells. • RNA-seq analysis on CD4+ T-cells treated with UA prior to activation led to no significant alterations in gene expression. • A mixture of UA and As demonstrated unique alterations in gene expression compared to As alone., Communities in the western region of the United States experience environmental exposure to metal mixtures from living in proximity to numerous unremediated abandoned uranium mines. Metals including arsenic and uranium co-occur in and around these sites at levels higher than the United States Environmental Protection Agency maximum contaminant levels. To address the potential effect of these metals on the activation of CD4+ T-cells, we used RNA sequencing methods to determine the effect of exposure to sodium arsenite (1 μM and 10 μM), uranyl acetate (3 μM and 30 μM) or a mixture of sodium arsenite and uranyl acetate (1 μM sodium arsenite + 3 μM uranyl acetate). Sodium arsenite induced a dose dependent effect on activation associated gene expression; targeting immune response genes at the lower dose. Increases in oxidative stress gene expression were observed with both sodium arsenite doses. While uranyl acetate alone did not significantly alter activation associated gene expression, the mixture of uranyl acetate with sodium arsenite demonstrated a combined effect relative to sodium arsenite alone. The results demonstrate the need to investigate metal and metalloid mixtures at environmentally relevant concentrations to better understand the toxicological impact of these mixtures on T-cell activation, function and immune dysregulation.

Arsenite is a toxic metallic pollutant known to cause hepatotoxic and nephrotoxic injuries. Costus afer Ker Gawl. is an indigenous medicinal plant used as therapy for numerous tissue disorders. Thus, this study investigated the protective potential of C. afer hexane leaf fraction (CALHF) on sodium arsenite-induced hepatic and renal injuries in albino rats. Twenty-five male albino rats were randomly distributed into five groups of five rats each. Group 1: rats administered orally with 0.5 ml of 0.9% saline; Group 2: untreated rats induced with 5 mg/kg body weight (b.w.) sodium arsenite (i.p.); Group 3: rats induced with sodium arsenite and treated with 10 mg/kg b.w. silymarin (hepatoprotective drug); Group 4 and 5: rats induced with sodium arsenite and treated with 100 and 200 mg/kg b.w. CALHF, respectively. CALHF was orally administered daily, while sodium arsenite was administered every 48 hours for 14 days. Thereafter, rats were sacrificed, blood was collected to estimate hepatic and nephrotic functions. Hepatic and renal function tests showed that 100 and 200 mg/kg CALHF and 10 mg/kg silymarin treated animals had significantly reduced (P < 0.05) plasma alanine aminotransferase, aspartate aminotransferase, creatinine and urea levels, when compared with those of untreated animals. C. afer hexane leaf fraction exhibited hepatoprotective and nephroprotective effects against sodium arsenite induced toxicity in rats.

This study assessed the probable effects of Ethanolic extract of Tanacetum parthenium (EETP) whole plant as hepatoprotective compound that acts on damaged liver due to administration of Sodium arsenite (NaAsO2 — 3mg/kg) in Wistar albino rats for a period of 28 days which results in alteration in Lipid peroxidation, antioxidant enzymes, biochemical factors, and liver enzyme. 30 animals were utilized for the study and are divided into five groups containing 6 rats each. Group –I treated as control received water, Group II-V were treated with sodium arsenite. Group-III received Vitamin-E (reference drug), Group IV treated with EETP 200 mg/kg dose and Group V treated with 400 mg/kg dose after hepatotoxicity induced by Sodium arsenite. Safeguarding effects of Ethanolic extract of Tanacetum parthenium whole plant were screened by analysis of the parameters like alanine transaminase, aspartate transaminase, alkaline phosphatase and total bilirubin, malondialdehyde, antioxidant enzymes. It was explored that administration of EETP at different doses could significantly decrease the enzymatic measures of AST, ALP, ALT, and TB concentration and increase catalase, GSH, GR and GPx levels in comparison with Sodium arsenite-induced control group. The data obtained from this experimental study prefigured the antioxidant potential of EETP and its potential hepatoprotective effects, and its beneficiary therapeutic effects on vandalization or disfigurement of liver due to Sodium arsenite induction in experimental animals.

Objectives Exposure to arsenic and hexavalent chromium is a major public health concern especially in the developing part of the world and there is paucity of information on reliable treatment modalilities. It is in this regard that this study evaluates the efficacy of methanol leaf extract of Rauvolfia vomitoria (MRV) when used as pretreatment agent against potassium dichromate (K2Cr2O7) and sodium arsenite (NaAsO2) exposure. Methods Swiss albino mice between 7 and 10 weeks old were divided into eight cohorts of five animals each. Treatment groups consisted of a distilled water control, MRV alone (275 mg/kg po daily), K2Cr2O7 (12.0 mg/kg, single ip injection) +/− MRV pretreatment, NaAsO2 (2.5 mg/kg, single ip injection) +/− MRV pretreatment, Na2AsO2 + K2Cr2O7 +/− MRV pretreatment. MRV was given for seven consecutive days, while K2Cr2O7 and NaAsO2 were injected on day seven of the experiment. The frequency of micronucleated polychromatic erythrocytes (mPCEs) was determined in bone marrow cells, while aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were assessed in the plasma. Hepatic glutathione (GSH), malondialdehyde (MDA), catalase (CAT) and glutathione-S-transferase (GST) levels were also determined. Results The NaAsO2 and K2Cr2O7 significantly (p2 and K2Cr2O7 further increased the levels of the markers. Furthermore, GSH and GST were significantly reduced by NaAsO2 or K2Cr2O7 or their combination. Pretreatment with MRV reversed the markers towards that of control. Conclusions Methanol extract of Rauvolfia vomitoria may therefore ameliorate NaAsO2 and K2Cr2O7-induced toxicities via reduction of oxidative stress and fortification of anti-oxidant system.

BackgroundHarsh environments surrounding fetuses and children can induce cellular damage in the developing brain, increasing the risk of intellectual disability and other neurodevelopmental disorders such as schizophrenia. However, the mechanisms by which early damage leads to disease manifestation in later life remain largely unknown. Previously, we demonstrated that the activation of heat shock (HS) signaling can be utilized as a unique reporter to label the cells that undergo specific molecular/cellular changes upon exposure to environmental insults throughout the body. Since the activation of HS signaling is an acute and transient event, this approach was not intended for long-term tracing of affected cells after the activation has diminished. In the present study, we generated new reporter transgenic mouse lines as a novel tool to achieve systemic and long-term tracking of affected cells and their progeny.MethodsThe reporter transgenic mouse system was designed so that the activation of HS signaling through HS response element (HSE) drives flippase (FLPo)-flippase recognition target (FRT) recombination-mediated permanent expression of the red fluorescent protein (RFP), tdTomato. With a priority on consistent and efficient assessment of the reporter system, we focused on intraperitoneal (i.p.) injection models of high-dose, short prenatal exposure to alcohol (ethanol) and sodium arsenite (ethanol at 4.0 g/kg/day and sodium arsenite at 5.0 mg/kg/day, at embryonic day (E) 12 and 13). Long-term reporter expression was examined in the brain of reporter mice that were prenatally exposed to these insults. Electrophysiological properties were compared between RFP+and RFP−cortical neurons in animals prenatally exposed to arsenite.ResultsWe detected RFP+neurons and glia in the brains of postnatal mice that had been prenatally exposed to alcohol or sodium arsenite. In animals prenatally exposed to sodium arsenite, we also detected reduced excitability in RFP+cortical neurons.ConclusionThe reporter transgenic mice allowed us to trace the cells that once responded to prenatal environmental stress and the progeny derived from these cells long after the exposure in postnatal animals. Tracing of these cells indicates that the impact of prenatal exposure on neural progenitor cells can lead to functional abnormalities in their progeny cells in the postnatal brain. Further studies using more clinically relevant exposure models are warranted to explore this mechanism.

The research was performed at Botany department, Nusrat Jahan College Rabwah Pakistan to screen stress tolerance level of soil microbes (pseudomonas and penicillium) taken from NARC (National Agricultural Research Centre) Pakistan against different levels of sodium arsenite stress (1 mg/L to 10 mg/L). The research was based on completely randomized design. Three drops were applied to microbes grown on CLED (cysteine-, lactose-, and electrolyte-deficient) media to determine zone of inhibition through disk, well and spread method, while control group was without sodium arsenite application. After application of various levels of arsenic stress organisms were incubated for 24 h at 37°C. After incubation, zones of inhibition were measured. Our study has shown that both micobes cannot overcome higher levels of arsenic stress because in higher stress petriplates, increased inhibitory zones were observed.

This paper presents results on the physicochemical properties of arsenic-containing substances—lewisite detoxification (destruction) products. Major attention is paid to the properties of hydrolytic sodium arsenite, a promising alternative industrial raw material for the production of high-purity arsenic and its compounds. Data are presented on the macro- and microcompositions of raw materials and temperature-dependent density and saturated vapor pressure of H3AsO4 solutions. The experimental data can be used in processing unconventional raw materials into extrapure arsenic-containing compounds.

In the scope of the study, the protective effect of hesperidin (HES), a flavanone glycoside, was investigated against sodium arsenite (NaAsO2, SA) induced heart and brain toxicity. For this purpose, 35 Sprague-Dawley male rats were divided into 5 different groups, 7 in each group. Physiological saline was given to the first group. Dose of 200 mg/kg of HES to the second group, 10 mg/kg dose of SA to the 3rd group, 100 mg/kg HES and 10 mg/kg SA to the 4th group, 200 mg/kg HES, and 10 mg/kg SA to the 5th group were given orally for 15 days. At the end of the study, biochemical, histopathological, and immunohistochemical examinations were performed on the heart and brain tissues of the rats. According to the results, SA increased malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels and decreased glutathione (reduced, GSH) level and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities in both tissues. Also, it increased cardiac lactate dehydrogenase (LDH) and creatine kinase isoenzyme-MB (CK-MB) activities and cardiac troponin-I level (cTn-I), cerebral acetylcholine esterase activity, nuclear factor kappa-B (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin-one beta (IL-1β), and cysteine aspartate-specific protease-3 (caspase-3) levels. In addition, as a result of histopathological examination, it was determined that SA damaged tissue architecture, and as a result of immunohistochemical examination, it increased cardiac Bcl-2-associated X protein (Bax) and cerebral glial fibrillary acidic protein (GFAP) expression. The results have also shown that HES co-treatment has an antioxidant, anti-inflammatory, antiapoptotic effect on SA-induced toxicity and aids to protect tissue architecture by showing a regulatory effect on all values. Consequently, it was determined that HES co-treatment had a protective effect on SA-induced heart and brain toxicity in rats.

Background Arsenic is an environmental contaminant of global concern. Consumption of ground water contaminated with inorganic arsenic (iAs) continues to be the major source of its exposure. The developing nervous system is especially vulnerable to environmental insults due to its higher rate of oxygen consumption and provision of weaker antioxidant (AOX) machinery. Objective Since oxidative stress has been reported as one of the major factors underlying iAs induced toxicity, the aim of the present study is to study the effect of two AOXs i.e., Alpha Lipoic Acid (ALA) and Curcumin (Cur) in developing cerebellum of rats exposed to arsenic during postnatal period. Materials and Methods The study was carried out on mother reared neonatal rat pups grouped as normal (Ia) and sham (vehicle) controls (Ib,c,d), while the experimental groups IIa/ IIb received sodium arsenite (NaAsO2) [(1.5/2.5 mg/kg body weight (bw)] alone or along with ALA (70 mg/kg bw)- IIIa/ IIIb or along with Cur (150 mg/kg bw)- IVa/ IVb. Behavioural, biochemical and immunohistochemical procedures were carried out to understand the underlying mechanisms. Results The observations indicated deficits in locomotor function, accumulation of iAs, increased levels of oxidative stress markers along with downregulation of the expression of proteins closely associated with synaptic functioning (Synaptophysin and Postsynaptic density protein95) in the cerebellum of iAs treated animals. Substantial recovery in all these parameters was observed in AOX co-treated groups. Conclusion Our results support the potential of ALA and Cur in amelioration of iAs induced developmental neurotoxicity. ALA and Cur can be proposed as dietary adjuvants amongst populations inhabiting areas with high iAs contamination as a safe and cost effective antidotes.

Chronic exposure to arsenic increases the risk of developing a variety of human cancers including lung carcinomas. However, the exact molecular mechanism underlying arsenic carcinogenicity remains largely unknown. Autophagy is a conserved catabolic process for maintaining cellular protein homeostasis whose defects might result in accumulation of dysfunctional organelles and damaged proteins thus promoting tumorigenesis. In the present study, we found that chronic exposure of human bronchial epithelial BEAS-2B cells to sub-lethal dose of sodium arsenite led to autophagy activation and induced an epithelial-to-mesenchymal transition (EMT) to enhance cell migratory and invasive capability. The malignant transformation was mediated via activation of MEK/ERK1/2 signaling. Importantly, inhibition of autophagy in these arsenic-exposed cells by pharmacological intervention or genetic deletion further promoted the EMT and increased the generation of inflammasomes. Both autophagy inhibitor and genetic deletion of autophagy core gene Beclin-1 produced similar effects. These results may suggest the important role of autophagy in sodium arsenite-induced lung tumorigenesis which may serve as a potential target in prevention and treatment of arsenic-imposed lung cancer.

Sodium arsenite is a toxicant with nephrotoxic potential. This study proves that combined extracts of Gongronema latifolium and Allium sativum can protect the kidney from this toxicity. Fifty male Wistar rats (115 - 280g) were obtained for this experiment. They were sustained with commercial rat’s feed pellets and water. The rats were grouped into ten groups of five rats each. Group1 rats were the normal control, Groups 2, 3 and 4 were administered with 10mg/kg bw of sodium arsenite intraperitoneally on day 1only, day 1 - 7 and day 7 only, respectively. Groups 5 and 6 rats were administered with 200mg/kg bw of Gongronema latifolium and Allium sativum respectively through oral gavaging from day 1 - 6, and 10mg/kg bw of sodium arsenite intraperitoneally on day 7, respectively. Group 7 rats were administered with 100mg/kgbw each of Gongronema latifolium and Allium sativum through oral gavaging from day 1 – 6, and 10mg/kgbw of sodium arsenite intraperitoneally on day 7. Groups 8 and 9 rats were administered with 200mg/kg bw of Gongronema latifolium only and Allium sativum only, respectively through oral gavaging. Group 10 rats were treated with 100mg/kg bw each of Gongronema latifolium and Allium sativum through oral gavaging from day 1 to 7. The rats were sacrificed 24 hours after the last administration and blood sample was collected for kidney function tests, and also the kidney for histological analysis. The results showed that the rats treated with sodium arsenite only, for different durations, had different degrees of nephrotic damage while those treated with single extracts and the toxicant showed moderate damage. The group treated with combined extracts and the toxicant was completely protected from all forms of nephrotic damage as evidently observed. KEYWORDS: Allium sativum; Gongronema latifolium; kidney; nephrotoxicity; rats; sodium arsenite..

Arsenic in the present times has caused lots of health hazards to humans. In developing countries like Bangladesh and India the high prevalence of contamination, the isolation and poverty of the rural population, and the high cost and complexity of arsenic removal systems have imposed a programmatic and policy challenge on an unprecedented scale. Although in India, arsenic poisoning in ground water in Gangetic belt especially the districts adjoining the river Ganges right from Eastern Uttar Pradesh, Bihar to West Bengal. These regions are the problem of concern as due to which major health related problems are arising. To combat the present problem, a pre-clinical study was carried out on Charles foster rats. They were treated with Sodium arsenite at the dose of 8 mg per kg body weight for 16 weeks to make arsenic model and upon these arsenic pre-treated rats seed extracts of Piper nigrum at the dose of 50 mg per kg body weight was administered for 4 weeks to study the antidote effects of this plant extract. The Piper nigrum extract not only eliminated the effects of arsenic but also reversed the normal physiological activity in the animal by normalising the activity of liver and kidney. The present study concludes that this novel plant extract possesses hepato-protective as well as nephro-protective activity against arsenic induced toxicity.

Background Arsenic exposure has become a matter of worldwide concern, which is associated with immune-related diseases. However, little is known about its effect on inflammatory immune-related homeostasis. The purpose of our study was to understand the potential tuning of above responses exerted by chronic arsenic exposure. Methods Kunming mice were treated with 25 and 50 mg/L sodium arsenite for 1, 3 and 12 months via drinking water. At different endpoints of arsenic exposure, all animals and the whole spleen of the mice were weighed. The total arsenic levels of spleen were determined by the HPLC-HG-AFS method. Splenic NF-κB, MAPK and NRF2 protein levels by treatment of 25 mg/L NaAsO2 for 1, 3 and 12 months and 25 mg/L and 50 mg/L NaAsO2 for 12 months were assessed by western blot. Total RNA of spleen was isolated and relative mRNA levels of Foxp3, Il-10, Tnf-α, Il-6, Ifn-γ, Il-1β and Il-12 were measured by real-time PCR. Results Our results shown that NF-κB were continuously activated with treatment of 25 mg/L arsenic from 1, 3 to 12 months and 50 mg/L arsenic for 12 months. The transcription factor Foxp3 increased at 1 month but decreased at 3 and 12 months no matter 25 or 50 mg/L arsenic exposure. However, cytokine Il-10 always showed increased trend in mice treated with 25 or 50 mg/L arsenic for 1, 3 and 12 months. The transcriptional profiles of Tnf-α, Il-1β, Il-6, Ifn-γ and Il-12 revealed transient elevation at 1 and 3 months but shown significant decrease at 12 months on the whole. In addition, the sustained activation of inflammatory MAPK and anti-oxidative Nrf2 signaling pathways were observed in mice exposed to arsenic for 1, 3 and 12 months. Conclusion In summary, our experiment in vivo suggested chronic arsenic exposure induces the time-dependent modulation of the inflammation and immunosuppression in spleen, which may be related to the activation of Tregs induced by MAPK/NF-κB as well as the increased transcription level of Foxp3 and Il-10.

Chronic arsenic poisoning is one of the serious health hazards in West Bengal, India, and Bangladesh. It occurs due to contaminated subsoil water. The aim of this study is conducted to find out the ameliorative effect of turmeric and P. foetida powder on experimentally induced arsenic toxicity in sheep. Twelve sheep were divided into four groups; groups I, II and III were orally administered with sodium arsenite at 6.6 mg/kg body weight for 133 days; groups I and II animals were treated by turmeric and P. foetida powders respectively at 500 mg/kg dose for the last 49 days; the fourth group was control. Arsenic content was estimated in faeces, urine and wool in every 15 days. Biochemical, haematological, antioxidant parameters and DNA fragmentation were also assessed. Turmeric and P. foetida powder treatment significantly (P < 0.05) increased arsenic elimination through faeces, urine and wool. Haemoglobin content and TEC were decreased in groups I, II and III; however, these were improved significantly (P < 0.05) by turmeric and P. foetida powder treatment. Increased activity of AST, ALT, blood urea nitrogen and plasma creatinine were significantly (P < 0.05) decreased in groups I and II. The reduced SOD and catalase activity were significantly (P < 0.05) restored at the end of the experiment in turmeric and P. foetida-treated groups. The test drugs are found significantly effective not only to eliminate arsenic from the body but also give protection from possible damage caused by arsenic exposure in sheep.

The testicular, sperm and endocrine protective properties of Chromolaena odorata (CA) in arsenic treated rats were investigated using forty male wistar rats (190-200g) grouped into 4 (A to D) of ten rats each. Oral administrations for 2 weeks of 0.2ml corn oil (A), 2.5mg/kg of sodium arsenite (B), 200mg/kg ethanol leaf extract (ELE) of CA (C), 200mg/kg ELE of CA and 2.5mg/kg sodium arsenite given at 1 hour interval (D) were done. Twenty-four hours after final administrations, semen, blood biochemical and hormonal analyses were carried out after sacrifice of the rats. Results revealed that Group C’s mean scrotal circumference, Left and Right testicular weights were highest across groups and significant compared to group B values (p

Endemic arsenism is widely distributed in the world, which can damage multiple organs, especially in skin and liver. The etiology is clear, but the mechanisms involved remain unknown. Ubiquitin-proteasome pathway (UPP) is the main pathway regulating protein degradation of which proteasome subunit beta type-5(PSMB5) plays a dominant role. This paper aims to study the role and mechanism of PSMB5 in sodium arsenite (NaAsO(2))–induced oxidative stress liver injury in L-02 cells. Firstly, L-02 cells were exposed to different concentrations of NaAsO(2) to establish a liver injury model of oxidative stress, and then mechanisms of oxidative stress were studied with carbobenzoxyl-leucyl-leucl-leucll-line (MG132) and knockdown PSMB5 (PSMB5-siRNA). The oxidative stress indicators, levels of 20S proteasome, the transcription and protein expression levels of PSMB5, Cu-Zn superoxide dismutase (SOD1), and glutathione peroxidase 1 (GPx1) were detected. The results demonstrated that NaAsO(2) could induce oxidative stress–induced liver injury and the activity of 20S proteasome and the protein expression of PSMB5, SOD1, and GPx1 decreased. After MG132 or PSMB5-siRNA pretreatment, the gene expression of PSMB decreased. After MG132 or PSMB5-siRNA pretreatment, and then L-02 cells were treated with NaAsO(2), the gene expression of PSMB remarkably decreased; however, the protein expression of SOD1 and GPx1 increased. Overall, NaAsO(2) exposure could induce oxidative stress liver injury and low expression of PSMB5 in L-02 cells, and PSMB5 might play an important role in the regulation of oxidative stress by regulating the expression of SOD1 and Gpx1.

Arsenic toxicity has gained at present an alarming global importance. Pulse crop is very sensitive to arsenic contaminated groundwater. In order to determine the phytotoxicity, effects of Sodium arsenite (NaAsO2) on seed germination and early development of Mung bean (Vigna radiata (L.) Wilczek cv. B-105) seedlings were investigated. Sodium arsenite had a toxic effect and posed a stress over germination parameters and early growth of mungbean seedlings. Considerable reduction in seed germination percentage and seedling vigour index was recorded due to arsenite. Sodium arsenite inhibited growth at very small concentrations such as 0.5µM. With the increase in concentration of sodium arsenite (0.5µM, 1µM, 2µM), significant decrease in seedling length i.e., shoot length and root length was observed. Arsenite was found to be more toxic for root growth than for shoot growth. Decrease in primary leaf area was also observed with increase in concentration of sodium arsenite. Number of stomata decreased and hence, reduction in stomatal density and stomatal index was also observed. Fresh weight and dry weight also reduced appreciably in the arsenite stressed seedlings. Treatment with 2µM concentration proved to be the most sensitive concentration for arsenite application by giving least values for seedling length and seedling vigour index.

Arsenic causes a wide range of neurological complications including cognitive impairment, short-term memory and concentration problems. The present study investigated effects of gallic acid (GA) against sodium arsenite (SA)-induced neurotoxicity in rats. Thirty-five adult male rats were randomly divided into five groups. Group 1 received normal saline (2 ml/kg, P.O.) for 21 days. Group 2 received SA (10 mg/kg, P.O., for 14 days). Groups 3 and 4 received GA (10 and 30 mg/kg, P.O., respectively) for 7 consecutive days prior to SA treatment and continued up to 21 days, parallel to SA administration. Group 5 received GA (30 mg/kg, P.O.) for 21 days. The long-term memory, motor performance, locomotor activity, and behavioral parameters were evaluated. The activity of glutathione peroxidase (GPx) and the level of MDA and glutathione (GSH) were measured in hippocampus, corpus striatum, and cortex of brains of rats. Histopathological parameters were also assessed. GA significantly reversed SA-induced reduction of step-through latency, latency to fall, and crossing, rearing, and grooming activity. GA significantly decreased SA-induced increased MDA level, and decreased GSH level and GPx activity in different parts of brain. Our results suggest that GA enhances endogenous antioxidant activity contributing to the improvement of SA-induced neural and behavioral dysfunction.

Background Nicotine is a major tobacco component and found at circulating concentrations in smokers’ bloodstreams. Although considered a non-carcinogenic substance, nicotine rapidly defuses to tissues after being inhaled, inviting effects on cellular physiology, particularly in the lung. Widespread increased use of nicotine-based e-cigarettes, especially in younger adults, creates an urgent need for improved understanding of nicotine’s potential to impact human health. Methods Biological and biochemistry methods were used to interrogate the potential for nicotine to weaken the genetic integrity of murine and human-lung epithelial cells. Results We demonstrate that nicotine potentiates the growth of the lung epithelial cells in a dose–response fashion. Nicotine elicits an acute increase in reactive oxygen species (ROS), which persists at moderately high levels throughout the duration of nicotine exposure. The aberrant increases in ROS appear to induce ER stress and UPR activation, as reflected by BIP upregulation and PERK phosphorylation. Furthermore, prolonged nicotine exposure interferes with p53 function triggered by sodium arsenite. Unless p53 is suppressed, persistent nicotine exposure does not induce colony formation by lung epithelial cells in soft agar. Conclusion The data suggest that nicotine treatment, by perturbing intracellular redox state and altering p53 function, can create a pro-tumorigenic environment in lung epithelium. The results suggest caution in using nicotine replacement therapies and e-cigarettes.

Arsenic is a ubiquitous environmental toxicant that has been associated with human respiratory diseases. In humans, arsenic exposure has been associated with increased risk of respiratory infection. Considering the existing epidemiological evidence and the well-established impact of arsenic on epithelial cell biology, we posited that the effect of arsenic exposure in epithelial cells could enhance viral infection. In this study, we characterized influenza virus A/WSN/33 (H1N1) infection in Madin-Darby Canine Kidney (MDCK) cells chronically exposed to low levels of sodium arsenite (75 ppb). We observed a 27.3-fold increase in viral matrix (M2) protein (24 hours postinfection [p.i.]), a 1.35-fold increase in viral mRNA levels, and a 126% increase in plaque area in arsenite-exposed MDCK cells (48 hours p.i.). Arsenite exposure resulted in 114% increase in virus attachment-positive cells (2 hours p.i.) and 224% increase in α-2,3 sialic acid-positive cells. Interestingly, chronic exposure to arsenite reduced the effect of the antiviral drug, oseltamivir in MDCK cells. We also found that exposure to sodium arsenite resulted in a 4.4-fold increase in viral mRNA levels and significantly increased cytotoxicity in influenza A/Udorn/72 (H3N2) infected BEAS-2B cells. This study suggests that chronic arsenite exposure could result in enhanced influenza infection in epithelial cells, and that this may be mediated through increased sialic acid binding. Finally, the decreased effectiveness of the anti-influenza drug, oseltamivir, in arsenite-exposed cells raises substantial public health concerns if this effect translates to arsenic-exposed, influenza-infected people.

Arsenic is identified as a known carcinogen and ubiquitously exists in nature. It appears that accumulation of inorganic arsenic (iAs) and its methylated metabolites in various tissues is closely correlated with the long-term toxicity and carcinogenicity of this metalloid. In this study, various arsenic species in murine tissues, especially in the cerebral cortex, cerebellum, and hippocampus, were determined after long-term exposure to 25, 50, 100, and 200 mg/L sodium arsenite in drinking water for 1 and 12 months. Our data showed that the amount of total arsenic (TAs) increased in an obvious dose-dependent manner in various tissues, and TAs levels were in the order of urinary bladder > brain > lung > liver > kidney > spleen. Furthermore, iAsIII and DMA could be observed in all tissues and brain regions with DMA being the predominant metabolite. The bladder, brain, and lung orderly contained the higher levels of DMA, while the liver, kidney, and spleen accumulated the higher proportion of iAsIII. MMA was preferentially accumulated in the lung and bladder of mice regardless of arsenic exposure doses or duration. What’s more, amazingly higher levels of MMA were observed in the hippocampus, which was distinguished from the cerebral cortex and cerebellum. Together with these results, our study clearly demonstrates that the accumulation of iAs and its methylated metabolites is tissue-specific and even not homogeneous among different brain regions in mice by long-term exposure to arsenite. Our study thus provides crucial information for recognizing arsenical neurotoxicity, and reducing the uncertainty in the risk assessment for this toxic metalloid.

Arsenic considered as one of the most hazardous chemical while arsenic poisoning is also one of the serious medical issues worldwide. Long term arsenic exposure is associated with bone degeneration. The exact mechanism involving arsenic induced bone degeneration remains unclear but, plentiful literature suggested that oxidative/nitrosative stress caused by generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) is one of the leading causes.Various treatment strategies are available for bone degeneration however, the suitable treatment for arsenic induced bone degeneration still lacks. In the current investigation, we evaluated the efficacy of chelation against arsenic induced bone degeneration in experimental rats. Male Sprague Dawley rats were exposed to sodium arsenite and dimethylarsinic acid (DMA) (50 ppm) for 18 weeks. After arsenic exposure, animals were treated with Monoisoamyl dimercaptosuccinic acid (MiADMSA) for three course of treatment (50 mg/kg, p.o., once daily for 5 days) with an interval of one week between two courses of treatment. MiADMSA minimizes the bone degeneration through reduction of oxidative stress (Reactive Oxygen Species, Reactive Nitrogen Species, and thiobarbituric reactive substances), alteration of antioxidant status (rGSH, Superoxide dismutase, Catalase) which led to the depletion in the levels of inflammatory markers like TNFα and IL-1β and alteration in the bone remodelling biomarkers like ALP, RANKL, and Runx2. It can be concluded from this study that MiADMSA could be an effective therapeutic strategy against arsenic induced bone degeneration and the possible mechanism could be the chelation of arsenic accompanied by the reduction in oxidative stress and inflammation.

Arsenic has been incriminated to cross the placental barrier both in humans as well as animals, which might be the putative cause of alteration(s) in developmental defects reported in fetuses. The present study was conducted to determine the teratogenic effect of arsenic induced toxicity, when given at the same level (0.0191 to 0.2080 mg/l) at which it is found in drinking water in different parts of India. Young male and female Wistar rats were randomly divided in four groups viz. I, II, III, and IV and were given sodium arsenite at a dose rate of 0.01 mg/l, 2.5 mg/l, 5 mg/l and distilled water respectively. The animals were kept for a period of 10 weeks prior to mating and fed sodium arsenite at the doses described, and pregnant females were sacrificed on 20th day of gestation and fetuses were collected. Gross anomalies of the foetus were examined. Half of each litter was processed for skeletal examination using Alizarin Red S staining while the remaining foetus was fixed in Bouin’s solution for visceral tissue evaluation. There were increased foetal resorption(s) in all treated groups. The foetal body weights and crown to rump lengths were significantly decreased and the percent gross, visceral and skeletal anomalies were significantly increased in fetuses of dams of arsenic treated groups in a dose dependent manner. The wrist drop, subcutaneous hematoma, internal hydrocephalus, cerebellar hypoplasia, microphthalmia, dilated renal pelvis, roundening of heart, incomplete ossification of skull bones, vertebrae, ribs, and agenesis of phalanges and caudal vertebrae were the most important foetal malformations. The occurrence of foetal gross, skeletal and visceral malformations were more severe in the group III followed by group II, suggesting the teratogenic nature of arsenic (sodium arsenite). It was concluded in the present study that albeit when arsenic was fed at lower dose mimicking the levels in the field conditions, it significantly caused developmental anomalies in the present study discernible as gross, visceral and skeletal anomalies.

Objective: Arsenic is the most prevalent and common environmental contaminant, found in drinking water with varying concentrations. Inorganic arsenic is involved in the generation of reactive oxygen species (ROS). The aim of present study was to determine the activities of antioxidant enzymes in liver of mice, changes with arsenic exposure and to determine whether it is associated with the induction of oxidative stress. Furthermore, we intended to determine whether swimming exercise can modulate the activities of antioxidant enzymes in vivo rendering protection to the liver of mice during arsenic exposure. Methods: Mouse model was established, mice were administrated with two different doses (10 and 20 mg/kg/day) of sodium arsenite. These mice underwent swimming exercise for about 8 weeks regularly. First group was negative control which received distilled water and no exercise. Group 2 and 4 were positive controls in which 10 mg/kg/day and 20 mg/kg/day of sodium arsenite were administered respectively, for 8 weeks. Group 3 and 5 underwent swimming exercise for 60 min daily along with 10 mg/kg/day and 20 mg/kg/day of sodium arsenite for same duration and act as treatment group. Results: Our results revealed that arsenic level was higher (0.13 mg/L) in the liver of mice lacking exercise in comparison to the exercise group (0.04 mg/L). Similarly, Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were found higher in mice lacking swimming exercises showing sodium arsenite had more severe pathological damages in liver as compared to the exercise groups. On the other hand, catalase (2.61 nmol/mg) and glutathione levels (1.25 nmol/mg) and expression of two antioxidant pathway genes i.e. NQO-1 and HO-1 were found elevated in exercise group. Conclusion: This study reveals that swimming alleviate the arsenic induced liver damages in mice through induction of Nrf2 antioxidant pathways. All these findings allowed us to speculate the involvement of swimming exercise which is responsible for hepato-protective activity. Keywords: Sodium arsenite, Swimming exercise, Antioxidants, Oxidative stress, Signaling pathway, Pathological damages

Background and Aim: Intoxication of arsenic in rats is known to result in neurological effects as well as liver and kidney dysfunction. Mucuna pruriens has been identified for its medicinal properties. The aim of the study was to investigate the protective effect of aqueous seed extract of M. pruriens on sodium arsenite-induced memory impairment, liver, and kidney functions in rats. Materials and Methods: The experiment was divided into short-term treatment (45 days) and long-term treatment (90 days), with each group divided into nine sub-groups consisting of six animals each. Sub-groups 1 and 2 served as normal, and N-acetylcysteine (NAC) controls, respectively. Sub-groups 3-9 received sodium arsenite in drinking water (50 mg/L). In addition, sub-group 4 received NAC (210 mg/kg b.wt) orally once daily, sub-groups 5-7 received aqueous seed extract of M. pruriens (350 mg/kg b.wt, 530 mg/kg b.wt, and 700 mg/kg b.wt) orally once daily and sub-groups 8 and 9 received a combination of NAC and aqueous seed extract of M. pruriens (350 mg/kg b.wt and 530 mg/kg b.wt) orally once daily. Following the treatment, the blood was drawn retro-orbitally to assess the liver (serum alanine transaminase [ALT], serum aspartate transaminase, and serum alkaline phosphatase) and kidney (serum urea and serum creatinine) functions. Learning and memory were assessed by passive avoidance test. Animals were sacrificed by an overdose of ketamine, and their Nissl stained hippocampal sections were analyzed for alterations in neural cell numbers in CA1 and CA3 regions. Results: In the short-term treatment, groups administered with M. pruriens 530 mg/kg b.wt alone and combination of NAC + M. pruriens 350 mg/kg b.wt exhibited a significant improvement in memory retention, less severe neurodegeneration, and decrease in serum ALT levels. In long-term treatment, groups administered with M. pruriens 700 mg/kg b.wt alone and combination of NAC+M. pruriens 350 mg/kg b.wt, respectively, showed better memory retention, decreased neural deficits, and reduced levels of kidney and liver enzymes. Conclusion: The seed extract of M. pruriens showed significant enhancement in memory and learning. The number of surviving neurons in the CA1 and CA3 regions also increased on treatment with M. pruriens. Serum ALT, serum urea, and serum creatinine levels showed significant improvement on long-term treatment with M. pruriens.

Objective: To investigate the protective effects of Mucuna (M.) pruriens against arsenic-induced testicular impairment in albino mice. Methods: Thirty-six male albino mice were divided into six groups, with 6 mice in each group. Group 1 received drinking water as the normal control. Groups 2 to 6 received sodium arsenite (40 mg/L) in drinking water. Group 3 received sodium arsenite (40 mg/L) and 300 mg/kg body weight (b.w.) of N-acetylcysteine. Group 4 received sodium arsenite (40 mg/L) and 500 mg/kg b.w. of M. pruriens. Group 5 received sodium arsenite (40 mg/L) and 1 000 mg/kg b.w. of M. pruriens. Group 6 received sodium arsenite (40 mg/L) and 2 000 mg/kg b.w. of M. pruriens. N-acetylcysteine and M. pruriens were administered orally once a day. Animals were subjected to the above treatments for 45 days. Animals were sacrificed with overdose of ketamine 24 h following drug administration. The testis was used for biochemical estimations (lipid peroxidation and glutathione), and the epididymis was used to determine the sperm count and morphology. Results: Sodium arsenite significantly decreased (P

Arsenic is a well-known element because of its toxicity. Humans as well as plants and animals are negatively affected by its exposure. Some countries suffer from high levels of arsenic in their tap water and soils, which is considered a primary arsenic-linked risk factor for living beings. Humans generally get exposed to arsenic by contaminated drinking waters, resulting in many health problems, ranging from cancer to skin diseases. On the other hand, the FDA-certified drug arsenic trioxide provides solutions for various diseases, including several types of cancers. This issue emphasizes the importance of speciation of the metalloid elements in terms of impacts on health. When species get exposed to arsenic, it affects the cells altering their involvement. It can lead to abnormalities in inflammatory mechanisms and the immune system which contribute to the negative impacts generated on the body. The poisoning originating from arsenic gives rise to various biological signs on the body which can be useful for the diagnosis. It is important to find true biomarkers for the detection of arsenic poisoning. In view of its application in medicine and biology, studies on understanding the biological activity of arsenic have increased. In this review, we aim at summarizing the current state of knowledge of arsenic and the mechanism behind its toxicity including genotoxicity, oxidative insults, epigenomic changes, and alterations in cellular signaling.