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Arsenic (As3+), a significant environmental pollutant that has garnered global attention, is widely recognized for its adverse effects on reproductive health. This study assesses the aphrodisiac activity of Dehydrozingerone (DHZ) against As3+ induced sexual dysfunction in male Wistar rats. Male Wistar rats were divided into control, As3+, and As3++DHZ groups. The As3+ group received 5 mg/kg sodium arsenite (NaAsO2) orally while As3++DHZ group received 50 mg/kg synthesized DHZ along with As3+ for 42 days. Following administration, mount and intromission latency, frequency, and average time were measured to assess aphrodisiac and reproductive toxicity in male Wistar rats which had 1:1 coitus with female rats. On days 14th, 28th, and 42nd, sexual behaviour was measured. Further on 43rd day, animals were sacrificed, blood was collected to measure oxidative parameters and LH hormone, and then testes were collected to profile reproductive damage. As3+ treated rats had lower sperm counts, motility, and abnormalities. These alterations reduced sexual hormones. In addition, As3+ toxicity depleted antioxidant indicators including SOD, GSH and elevated ROS. Compared to the As3+ group, As3++DHZ showed a substantial (p < 0.05) increase in sperm count, motility, and reduced abnormalities. DHZ also reversed the rise in luteinizing hormone caused by As3+ therapy, restored oxidative indicators, and improved seminiferous tubule structural damage. 42 days As3+ exposure slightly increased rats' sexual desire but not sperm quality. However, As3++DHZ lower libido and sperm quality. Thus, DHZ therapy enhanced rat sexual desire and sperm quality compared to As3+. [ABSTRACT FROM AUTHOR]

Groundwater contamination in India exposes an estimated 70 million people to arsenic. Over 10 million people in the state of Bihar (India) are at risk of arsenic poisoning. As reported 27 districts of the state's thirty-eight districts are under a state of catastrophe. Symptoms noticed by those who have been exposed to the arsenic caused disease are-lack of appetite, neurobehavioral problems, hyperkeratosis, and melanosis on the skin. So, this study's primary objective is to find novel approaches to treat arsenic poisoning in rats using the Charles Foster model. Following permission from the Institutional Animal Ethics Committee, the animals were divided into three groups: one group served as a control, the second group received arsenic treatment, and the third group received Ganoderma lucidum extract after arsenic treatment. For the arsenic group, the rats were given 8 mg/kg body weight of sodium arsenite orally every day for 90 days, and then for 60 days, they were given 80 mg/Kg body weight of Ganoderma lucidum extract via gavage. Their biochemical values, including those of the liver and kidneys, were found to be increased. In addition, their levels of free radicals, including lipid peroxidation, were measured and found to be substantially higher. In addition, the levels of arsenic in the kidney and liver tissue were very high. However, biochemical and lipid peroxidation levels were significantly restored after administration of Ganoderma lucidum ethanolic extract. Arsenic levels in rat liver and kidney tissues were also found to be reduced. Ganoderma lucidum has a therapeutic impact against arsenicinduced toxicity, according to the present research. [ABSTRACT FROM AUTHOR]

Arsenic contamination is a serious issue throughout the world and is substantial risk factor in most of the countries including India. Chronic arsenic exposure from drinking water to humans is causing major public health related issues. The present study aims to investigate the ameliorative effect of Citrullus lanatus (Watermelon) seeds against arsenic induced reproductive function and testicular toxicity in Charles Foster rats. In the present study, twenty-four male Charles Foster rats (120±5gm). The study group includes group - I (n=6) as control, and group - II (n=18) treated with sodium arsenite (8 mg per Kg body weight per day) for 90 days. The group - II was furthermore divided into three sub-groups, Group - II-a, Group - II-b and Group - II-c. The group - II-a were sacrificed to see the effect of arsenic toxicity effect after arsenic exposure. Group - II-b was left with normal food and water for next 60 days to observe auto recovery. The group - II-c rats were administered with Citrullus lanatus (Watermelon) hydroxyl ethanolic seeds extract at the dose of 400 mg per Kg body weight per day for 60 days for 90 days upon pre-treated sodium arsenite treated group (8 mg per kg body weight). After completion of the experiment, all the treated group of animals were sacrificed for biochemical, hormonal assay, histopathological, testicular and reproductive functions study. In the arsenic treated rats' group, there was significant (p<0.001) changes in serum levels of SGPT, SGOT, urea, uric acid and creatinine as well as in haematological parameters. There was decrease in the sperm counts and sperm motility accompanied by an increased incidence of sperm abnormalities and hormonal imbalance denotes infertility condition. In contrast, after the administration with C.lanatus (Watermelon) seeds hydroxy-ethanolic extract upon arsenic treated rats group, there was significant (p<0.001) improvement observed in the reproductive, hepatic and renal parameters. In the arsenic intoxicant rats' group, after administration with C. lanatus (Watermelon) seeds hydroxyl ethanolic extract, there was significant (p<001) reduction in the arsenic concentration in blood, liver, and kidney tissues as well as serum lipid peroxidation. The histopathological study also showed the C. lanatus (Watermelon) seeds hydroxy ethanolic extract significantly restored the cellular integrity of testicular cells leading to normal functioning of it against arsenic induced toxicity. [ABSTRACT FROM AUTHOR]

In Bihar, an estimated 10 million are exposed to arsenic poisoning through drinking of water. The entire Gangetic plain region people are exposed to arsenic poisoning which is causing lot of health hazards including the problem of infertility. Usually, the infertility problem is associated with the hormonal imbalances and arsenic is a xenoestrogen toxicant which plays major role in causing the imbalance. Moreover, this reproductive disorder has become a major problem in the society causing social stigma in the exposed population. Therefore, there is indeed need for search of novel drug which may play major role in combating the present problem. The present study therefore aims to discover fertility booster against the arsenic induced male reproductive toxicity in animal models. The current study was conducted on Charles Foster Rats after approval by the Animal Ethics Committee of the Institution. A total of n=18 rats (12 weeks of age) with a mean weight of 160±20 g was used in this study. The study group consisted of n=6 controls and n=12 orally treated with sodium arsenite at a dose of 8mg/Kg b.w per day for 40 days. The n= 6 animals were dissected and rest n=6 was administered orally with Asparagus racemosus root ethanolic extract at the dose of 400mg/Kg b.w per day for 40 days. At the end of the entire experiment, all the animals were dissected out and their reproductive organs were taken out especially epididymis for sperm counts, sperm motility, sperm mortality, sperm morphology. The blood samples were taken for hormonal determination (testosterone and luteinizing hormone), as well as for haematological and biochemical analysis. The study showed a severe degeneration in the reproductive organs of the arsenictreated rats. There were degenerative changes in sperm count, sperm motility, sperm mortality, sperm morphology, in the hormonal parameters, as well as in the hematological and biochemical parameters in the arsenic treated rats. But, in the Asparagus racemosus root ethanolic extract treated group, there was significant normalization in all these parameters. Therefore, in the present study, the Asparagus racemosus root ethanolic extract at the dose of 400mg/Kg/body weight per day shows significant fertility boost effect on arsenic induced Charles Foster rats. [ABSTRACT FROM AUTHOR]

Arsenic is a toxic environmental pollutant heavy metal, and one of its critical target tissues in the body is the liver. Carvacrol is a natural phytocompound that stands out with its antioxidant, anti‐inflammatory, and antiapoptotic properties. The current study aims to investigate the protective feature of carvacrol against sodium arsenite‐induced liver toxicity. Thirty‐five Sprague‐Dawley male rats were divided into five groups: Control, Sodium arsenite (SA), CRV, SA + CRV25, and SA + CRV50. Sodium arsenite was administered via oral gavage at a dose of 10 mg/kg for 14 days, and 30 min later, CRV 25 or 50 mg/kg was administered via oral gavage. Oxidative stress, inflammation, apoptosis, autophagy damage pathways parameters, and liver tissue integrity were analyzed using biochemical, molecular, western blot, histological, and immunohistological methods. Carvacrol decreased sodium arsenite‐induced oxidative stress by suppressing malondialdehyde levels and increasing superoxide dismutase, catalase, glutathione peroxidase activities, and glutathione levels. Carvacrol reduced inflammation damage by reducing sodium arsenite‐induced increased levels of NF‐κB and the cytokines (TNF‐α, IL‐1β, IL‐6, RAGE, and NLRP3) it stimulates. Carvacrol also reduced sodium arsenite‐induced autophagic (Beclin‐1, LC3A, and LC3B) and apoptotic (P53, Apaf‐1, Casp‐3, Casp‐6, Casp‐9, and Bax) parameters. Carvacrol preserved sodium arsenite‐induced impaired liver tissue structure. Carvacrol alleviated toxic damage by reducing sodium arsenite‐induced increases in oxidative stress, inflammation, apoptosis, and autophagic damage parameters in rat liver tissues. Carvacrol was also beneficial in preserving liver tissue integrity. [ABSTRACT FROM AUTHOR]

BackgroundArsenic exposure is a common and important environmental and occupational hazardous factor in China, and arsenic-induced insulin resistance (IR) has attracted widespread attention as a negative health outcome to the population. ObjectiveTo explore part of the mechanism of hepatic IR induced by arsenic exposure based on the peroxisome proliferators-activated receptors γ (PPARγ)/ glucose transporter 4 (GLUT4) pathway, and to investigate potential effects of Ginkgo biloba extract (GBE) on hepatic IR induced by arsenic exposure and associated mechanism of action. MethodsThe target of drug action was predicted by network pharmacology and verified by in vivo and in vitro experiments. In vivo experiments: 48 SPF C57BL/6J male mice were divided into 4 groups, including control group, 50 mg·L−1 NaAsO2 model group (NaAsO2), 50 mg·L−1 NaAsO2+10 mg·kg−1 GBE intervene group (NaAsO2+GBE), and 10 mg·kg−1 GBE group (GBE), 12 mice in each group. The animals were given free access to purified water containing 50 mg·L−1 NaAsO2, or given intraperitoneal injection of normal saline containing 10 mg·kg−1 GBE once per week. After 6 months of exposure, blood glucose detection, intraperitoneal glucose tolerance test (IPGTT), and insulin tolerance test (ITT) were performed. Serum and liver tissues were collected after the mice were neutralized, liver histopathological sections were obtained, serum insulin levels, liver tissue glycogen content, glucose content were detected by enzyme linked immunosorbent assay (ELISA), and the expression of PPARγ and GLUT4 proteins was detected by Western blot (WB). In vitro experiments: HepG2 cells were divided into 4 groups, including control group, 8 μmol·L−1 NaAsO2 group (NaAsO2), 8 μmol·L−1 NaAsO2 + 200 mg·L−1 GBE intervene group (NaAsO2+GBE), and 200 mg·L−1 GBE group (GBE). The levels of glycogen and glucose were detected by ELISA, and the expression of PPARγ and GLUT4 proteins was detected by WB. Results A strong binding effect between GBE and PPARγ was revealed by network pharmacology. In in vivo experiments, the NaAsO2 group exhibited an elevated blood glucose compared to the control group, and the NaAsO2+GBE group showed a decreased blood glucose compared to the NaAsO2 group (P

Arsenic (As) contamination poses significant environmental and health concerns globally, particularly in regions with high exposure levels due to anthropogenic activities. As phytoremediation, particularly through the hyperaccumulator fern Pteris vittata, offers a promising approach to mitigate arsenic pollution. Bacteria and mycorrhizal fungi colonizing P. vittata roots are involved in As metabolism and resistance and plant growth promotion under stressful conditions. A total of 45 bacterial strains were isolated from bulk soil and the rhizosphere of mycorrhizal P. vittata growing in an industrial As-polluted site. Bacteria were characterized by their plant-beneficial traits, tolerance to sodium arsenate and arsenite, and the occurrence of As-resistant genes. This study highlights differences between the culturable fraction of the microbiota associated with the rhizosphere of mycorrhizal P. vittata plants and the bulk soil. Moreover, several strains showing arsenate tolerance up to 600 mM were isolated. All the bacterial strains possessed arsC genes, and about 70% of them showed arrA genes involved in the anaerobic arsenate respiration pathway. The possible exploitation of such bacterial strains in strategies devoted to the assisted phytoremediation of arsenic highlights the importance of such a study in order to develop effective in situ phytoremediation strategies. [ABSTRACT FROM AUTHOR]

Arsenic (As) is globally detected in drinking water and food products at levels repeatedly surpassing regulatory thresholds. Several neurological and mental health risks linked to arsenic exposure are proposed; however, the nature of these effects and their association with the chemical forms of arsenic are not fully understood. Gaining a clear understanding of the etiologies and characteristics of these effects is crucial, particularly in association with developmental exposures where the nervous system is most vulnerable. In this study, we investigated the effects of early developmental exposure (6- to 120-h postfertilization [hpf]) of larval zebrafish to environmentally relevant concentrations of arsenic species—trivalent/pentavalent, inorganic/organic forms—on developmental, behavioral, and molecular endpoints to determine their effect on stress response and their potential association with stress-related disorders. At 120 hpf, the developing larvae were assessed for a battery of endpoints including survival, developmental malformities, background activity, and behavioral responses to acute visual and acoustic stimuli. Pooled larval samples were analyzed for alterations in the transcript levels of genes associated with developmental neurotoxicity and stress-related disorders. Developmental exposures at target concentrations did not significantly alter survival, overall development, or background activity, and had minor effects on developmental morphology. Sodium arsenate and monomethylarsonic acid exaggerated the behavioral responses of larval zebrafish, whereas sodium arsenite depressed them. Sodium arsenate induced significant effects on molecular biomarkers. This study highlights the effects of developmental exposure to arsenicals on the behavioral stress response, the role chemical formulation plays in exerting toxicological effects, and the possible association with stress-related disorders. [ABSTRACT FROM AUTHOR]

Groundwater arsenic is a notorious toxicant and exposure to environmentally relevant concentrations persists as a healthcare burden across the world. Arsenic has been reported to jeopardize the normal functioning of the immune system, but there are still gaps in the understanding of thymic T cell biology. Immunotoxic influence of arsenic in thymic integrity demands a potent restorative molecule. The objectives of this study were to examine key signaling cross‐talks associated with arsenic‐induced immune alterations in the thymus and propose melatonin as a potential candidate against immunological complications arising from arsenic exposure. Swiss albino mice were exposed to sodium arsenite (0.05 mg/L; in drinking water) and melatonin (IP:10 mg/kg BW) for 28 days. Melatonin successfully protected thymus from arsenic‐mediated tissue degeneration and maintained immune homeostasis including T cell maturation and proliferation by mitigating oxidative stress through Nrf2 upregulation. Additionally, melatonin exerted ameliorative effect against arsenic‐induced apoptosis and inflammation by inhibiting p53‐mediated mitochondrial cell death pathway and NF‐κB‐p65/STAT3‐mediated proinflammatory pathway, respectively. For the first time, we showed that arsenic‐induced profibrotic changes were inhibited by melatonin through targeting of inflammation‐associated EMT. Our findings clearly demonstrate that melatonin can be a viable and promising candidate in combating arsenic‐induced immune toxicity with no collateral damage, making it an important research target. [ABSTRACT FROM AUTHOR]

In recent years, the increase in environmental pollutants has been one of the most important factors threatening human and environmental health. Arsenic, a naturally occurring element found in soil, water, and air, easily enters the human body and leads to many metabolic disorders. In this study, we focused on the possible protective effects of N-acetylcysteine (NAC) against sodium arsenite (As)-induced toxic effects on embryonic fibroblast cells. The effects of As and NAC treatment on cells were evaluated, including cytotoxicity, oxidative stress, and apoptosis. Embryonic fibroblast cells were exposed to As (ranging from 0.01 μM to 10 μM) and NAC (at a concentration of 2 mM) for 24 h. The assessment of cytotoxicity markers, such as cell viability and lactate dehydrogenase (LDH), showed that As significantly reduced cell viability and increased LDH levels. Furthermore, we observed that As increased the amount of reactive oxygen species (ROS) in the cell, decreased the activity of antioxidant enzymes, and triggered apoptosis in cells. Additionally, our research revealed that the administration of NAC mitigates the detrimental effects of As. The results showed that As exerted hazardous effects on embryonic fibroblast cells through the induction of oxidative stress and apoptosis. In this context, our study provides evidence that NAC may have a protective effect against the toxicity of As in embryonic fibroblast cells. [ABSTRACT FROM AUTHOR]

The iPSC-derived 3D models are considered to be a connective link between 2D culture and in vivo studies. However, the sensitivity of such 3D models is yet to be established. We assessed the sensitivity of the hiPSC-derived 3D spheroids against 2D cultures of neural progenitor cells. The sub-toxic dose of Sodium Arsenite (SA) was used to investigate the alterations in miRNA-proteins in both systems. Though SA exposure induced significant alterations in the proteins in both 2D and 3D systems, these proteins were uncommon except for 20 proteins. The number and magnitude of altered proteins were higher in the 2D system compared to 3D. The association of dysregulated miRNAs with the target proteins showed their involvement primarily in mitochondrial bioenergetics, oxidative and ER stress, transcription and translation mechanism, cytostructure, etc., in both culture systems. Further, the impact of dysregulated miRNAs and associated proteins on these functions and ultrastructural changes was compared in both culture systems. The ultrastructural studies revealed a similar pattern of mitochondrial damage, while the cellular bioenergetics studies confirm a significantly higher energy failure in the 2D system than to 3D. Such a higher magnitude of changes could be correlated with a higher amount of internalization of SA in 2D cultures than in 3D spheroids. Our findings demonstrate that a 2D culture system seems better responsive than a 3D spheroid system against SA exposure. [ABSTRACT FROM AUTHOR]

The present study aims to develop the antidote against arsenic induced male reproductive toxicity in animal models. The study was carried out on Charles Foster rats after the approval from Institutional Animal Ethics Committee. A total of n=18, rats (12 weeks old) of an average weight of 160 ± 20 g were used for the study. The study group included n=6 control and n= 12 treated with sodium arsenite orally at the dose of 8mg/Kg body weight daily for 40 days. The n= 6 animals were dissected and rest n=6 was administered orally with Curcuma longa rhizome ethanolic extract at the dose of 600mg/Kg body weight per day for 40 days. At the end of the entire experiment, all the animals were dissected out and their reproductive organs were taken out, especially epididymis for sperm counts, sperm motility, sperm mortality, sperm morphology. The blood samples were collected for the hormonal assay (testosterone and luteinizing hormone), as well as for hematological and biochemical analysis. The study showed, high magnitude of degeneration in the reproductive organs of the rats in the arsenic treated group. There were degenerative fluctuations in the sperm counts, sperm motility, sperm mortality, sperm morphology and in the hormonal parameters, as well as in the hematological and biochemical parameters in the arsenic treated rats. But, after the administration of Curcuma longa, there was significant amelioration in all these parameters. Therefore, the present study shows that Curcuma longa plays vital role to combat arsenic induced male reproductive toxicity. [ABSTRACT FROM AUTHOR]

The current work aims to prevent the adverse effects of arsenic poisoning in animal models by using a medicinal plant extract. The animals (Charles Foster rats) were exposed to Sodium arsenite at a dose of 8 mg per kg body weight for 90 days in order to develop an arsenic model. Leaf extract of Calendula officinalis at a dose of 200 mg per kg body weight was administered to these arsenic treated rats for 60 days to study the preventive effects of this plant extract. The study found that arsenic poisoning had an adverse effect on rats at the haematological, biochemical, and histopathological levels, but there was considerable normalization in the animal at all of these levels after the leaf extract administration of Calendula officinalis. As a result, it has ameliorative qualities against arsenic-induced toxicity and may be used therapeutically as a preventative medication. [ABSTRACT FROM AUTHOR]

Arsenic poisoning in groundwater is the most common environmental pollutant, which is leading to serious pollution worldwide. Chronic arsenic exposure from drinking water to humans causes major public health-related issues. The present study was conducted to investigate the antidote effects of Foeniculum vulgare (Fennel) against arsenic-induced hepatotoxicity and testicular toxicity in Charles Foster rats. In the present study, twenty-four male Charles Foster rats (120±5gm) were divided into four Groups (n=6), where control Group-I received a normal diet and water; Group - II and Group - III received sodium arsenite (8 mg per kg body weight per day) for 90 days. Group III was left with a normal diet and water for the next 60 days for auto-recovery. The group IV rats were administered Foeniculum vulgare (Funnel) hydroxyl ethanolic seed extract at a dose of 150 mg per kg body weight for 60 days in a 90-day pre)treated sodium arsenite group (8 mg per kg body weight). After complete dose duration, all the treated animals were sacrificed the same day for haematological, biochemical, hormonal, and histopathological studies. In the arsenic treated rats, there were significant (p<0.001) changes in serum levels of SGPT, SGOT, urea, uric acid and creatinine as well as in haematological parameters. And there was also decease in the sperm count and sperm motility, accompanied by an increased incidence of sperm abnormalities and hormonal imbalances leading to infertility. In contrast, after the administration of F. vulgare seeds hydroxy-ethanolic extract to arsenic-treated rats, significant (p<0.001) improvements were observed in hepatic and renal parameters as well as haematological parameters. In the arsenic-intoxicant rat, after administration of F. vulgare seeds hydroxyl ethanolic extract, there was a significant (p<001) reduction in the arsenic concentration in blood, liver, and kidney tissues as well as serum LPO. The histopathological study also showed the F. vulgare seeds hydroxy-ethanolic extract significantly restored the cellular integrity of testicular cells, leading to their normal functioning against arsenic-induced toxicity. [ABSTRACT FROM AUTHOR]

The presence of arsenic (As) metalloid in groundwater poses serious threat to human and animal’s health. Approx. 300 million people of about 105 countries in the world are affected due to arsenite poisoning. Except mitigation there is no such mode by which the population can be prevented from being exposed to arsenic. Elaeocarpus sphaericus (E. sphaericus) is widely used in the folk medicine system for the treatment of various diseases. Hence, present study aimed to investigate the Bio-remedial Impact of ESSE against As-Induced Nephrotoxicity in Charles foster rats. Male twenty-four rats (weighing 160 ± 20 g) were randomly assigned into two groups, where Group-I (n=6) rats were used as control. Group-II (n=18) rats were treated with sodium arsenite at 8 mg/Kg body weight for 90 days daily and then further divided into three sub-groups. Sub-Group I (n=6); rats were sacrificed and data were collected, Sub-Group II (n=6); rats were left for 60 days for auto recovery (as As-pre-treated group), and Sub-Group II (n=6); rats were administrated with E. sphaericus at 20mg/kg body weight for 60 days. After the completion of entire experimental dose all the control and treatment group were sacrificed to evaluate the various parameters. As-Induced rats had Significant (p<0.0001) alteration in haematological parameters. As-Induced serum levels of urea, uric acid, creatinine and albumin had significant (p<0.0001) alteration. Level of MDA and BUN were significantly (p<0001) increased. However, ESSE administration significantly reduced the adverse effect related to test of nephrological functions, MDA level significantly (p<0.0001) reduced. Dose dependent ESSE administration combat As)Induced toxicity and significantly (P<0.0001) normalise the level of haematological parameters. Hence, the study concluded that E. sphaericus seed might be used as a nutritional supplement to combat the arsenic led toxicity among the exposed population. [ABSTRACT FROM AUTHOR]

Objective(s): This study aimed to investigate the effects of zingerone (ZNG) treatment on testicular toxicity in rats induced by sodium arsenite (SA).Materials and Methods: In the study, five groups were formed (n=7) and the experimental groups were designated as follows; Vehicle group, ZNG group, SA group, SA+ZNG 25 group, and SA+ZNG 50 group. While SA was administered orally to rats at 10 mg/kg/bw, ZNG was given to rats orally at 25 and 50 mg/kg/bw doses for 14 days.Results: As a result of the presented study, an increase was observed in the MDA contents of the testicular tissue of the rats administered SA, while significant decreases were observed in GSH levels, SOD, CAT, and GPx activities. The mRNA transcript levels of the pro-inflammatory genes NF-κB, TNF-α, IL-1β, and IL-6 were triggered after SA administration. Additionally, SA administration caused inflammation by increasing RAGE, NLRP3, and JAK-2/STAT3 gene expression. Moreover, endoplasmic reticulum (ER) stress occurred in the testicular tissues of SA-treated rats and thus ATF-6, PERK, IRE1, and GRP78 genes were up-regulated. SA caused apoptosis by up-regulating Bax and Caspase-3 expressions and inhibiting Bcl-2 expression in testicles. SA caused histological irregularities in the testicles, resulting in decreased sperm quality.Conclusion: ZNG treatment reduced SA-induced oxidative stress, ER stress, inflammation, apoptosis, and histological irregularities in the testicles while increasing sperm quality. As a result, it was observed that ZNG could alleviate the toxicity caused by SA in the testicles.

Objective(s): In the present study, the potential protective effects of zingerone (ZNG) against sciatic nerve damage caused by sodium arsenite (SA), a common environmental pollutant, were evaluated by various biochemical, molecular, and histological methods.Materials and Methods: In the study, SA and ZNG were given to 35 male Sprague Dawley rats for 14 days. At the end of the period, the sciatic nerve tissues were taken and the markers involved in oxidative stress, endoplasmic reticulum stress, inflammation, and apoptosis were analyzed.Results: The data obtained showed that SA decreased glutathione (GSH) levels and increased malondialdehyde (MDA) levels in the sciatic nerve tissue. However, it was determined that these markers approached the control group levels due to the anti-oxidant properties of ZNG. While SA triggered endoplasmic reticulum stress and apoptosis pathways, ZNG suppressed them. Moreover, SA up-regulated inflammatory markers such as nuclear factor kappa-B (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin-1-beta (IL-1β), and neuronal nitric oxide synthases (nNOS) in the sciatic nerves and caused neuro-inflammation and inhibited cell survival by suppressing serine/threonine-protein kinase 2 (Akt2) and forkhead box protein O1 (FOXO1) genes. It has also been shown histopathologically that SA causes degeneration in the sciatic nerves. In contrast, ZNG suppressed neuro-inflammation, activated Akt2/FOXO1 signaling, and repaired histological irregularities.Conclusion: In general, SA caused oxidative stress, inflammation, ER stress, and apoptosis in the sciatic nerves of rats, causing damage to the tissues, however, ZNG suppressed these pathways and protected the sciatic nerves from the destructive effect of SA.

NaAsO2 is known as a harmful pollutant all over the world, and many chronic heart diseases can be attributed to its prolonged exposure in NaAsO2-contaminated water. Therefore, considering the anti-inflammatory and antioxidant effects of betaine (BET), in this study, our team investigated the cardioprotective effects of this phytochemical agent on sodium arsenite (NaAsO2)-induced cardiotoxicity. Forty male mice were randomly divided into 4 groups: (I) Control; (II) BET (500 mg/kg); (III) NaAsO2 (50 ppm); and (IV) NaAsO2 + BET. NaAsO2 was given to the animals for 8 weeks, but BET was given in the last two weeks. After decapitation, inflammatory factors and biochemical parameters were measured, and Western blot analyses were performed. BET decrease the activity level of alanine aspartate aminotransferase, creatine kinase MB, thiobarbituric acid reactive substances level, inflammatory factors (tumor necrosis factor-α) content, and nuclear factor kappa B expression. Furthermore, BET increased cardiac total thiol and activity levels of catalase, superoxide dismutase, and glutathione peroxidase and nuclear factor erythroid-2 expression. Hence, the administration of BET ameliorated the deleterious effects stemming from the imbalance of oxidative and antioxidant pathways and histopathological alterations observed in NaAsO2-intoxicated mice, thereby attenuating oxidative stress-induced damage and inflammation. [ABSTRACT FROM AUTHOR]

Lysine specific demethylase 1 (LSD1) is a histone demethylase that specifically catalyzes the demethylation of histone H3K4 (H3K4me1/2) and regulates gene expression. In addition, it can mediate the process of autophagy through its demethylase activity. Sestrin2 (SESN2) is a stress‐induced protein and a positive regulator of autophagy. In NaAsO2‐induced mouse fibrotic livers and activated hepatic stellate cells (HSCs), LSD1 expression is decreased, SESN2 expression is increased, and autophagy levels are also increased. Overexpression of LSD1 and silencing of SESN2 decreased the level of autophagy and attenuated the activation of HSCs induced by NaAsO2. LSD1 promoted SESN2 gene transcription by increasing H3K4me1/2 in the SESN2 promoter region. 3‐methyladenine (3‐MA) and chloroquine were used to inhibit autophagy of HSCs, and the degree of activation was also alleviated. Taken together, LSD1 positively regulates SESN2 by increasing H3K4me1/2 enrichment in the SESN2 promoter region, which in turn increases the level of autophagy and promotes the activation of HSCs. Our results may provide new evidence for the importance of LSD1 in the process of autophagy and activation of HSCs induced by arsenic poisoning. Increasing the expression and activity of LSD1 is expected to be an effective way to reverse the autophagy and activation of HSCs induced by arsenic poisoning. [ABSTRACT FROM AUTHOR]

Although the toxicity of arsenic depends on its chemical forms, few studies have taken into account the ambiguous phenomenon that sodium arsenite (NaAsO2) acts as a potent carcinogen while arsenic trioxide (ATO, As2O3) serves as an effective therapeutic agent in lymphoma, suggesting that NaAsO2 and As2O3 may act via paradoxical ways to either promote or inhibit cancer pathogenesis. Here, we compared the cellular response of the two arsenical compounds, NaAsO2 and As2O3, on the Burkitt lymphoma cell model, the Epstein Barr Virus (EBV)-positive P3HR1 cells. Using flow cytometry and biochemistry analyses, we showed that a NaAsO2 treatment induces P3HR1 cell death, combined with drastic drops in ΔΨm, NAD(P)H and ATP levels. In contrast, As2O3-treated cells resist to cell death, with a moderate reduction of ΔΨm, NAD(P)H and ATP. While both compounds block cells in G2/M and affect their protein carbonylation and lipid peroxidation, As2O3 induces a milder increase in superoxide anions and H2O2 than NaAsO2, associated to a milder inhibition of antioxidant defenses. By electron microscopy, RT-qPCR and image cytometry analyses, we showed that As2O3-treated cells display an overall autophagic response, combined with mitophagy and an unfolded protein response, characteristics that were not observed following a NaAsO2 treatment. As previous works showed that As2O3 reactivates EBV in P3HR1 cells, we treated the EBV- Ramos-1 cells and showed that autophagy was not induced in these EBV- cells upon As2O3 treatment suggesting that the boost of autophagy observed in As2O3-treated P3HR1 cells could be due to the presence of EBV in these cells. Overall, our results suggest that As2O3 is an autophagic inducer which action is enhanced when EBV is present in the cells, in contrast to NaAsO2, which induces cell death. That's why As2O3 is combined with other chemicals, as all-trans retinoic acid, to better target cancer cells in therapeutic treatments. [ABSTRACT FROM AUTHOR]

Objective(s): This study aimed to investigate the effects of zingerone (ZNG) treatment on testicular toxicity in rats induced by sodium arsenite (SA). Materials and Methods: In the study, five groups were formed (n=7) and the experimental groups were designated as follows; Vehicle group, ZNG group, SA group, SA+ZNG 25 group, and SA+ZNG 50 group. While SA was administered orally to rats at 10 mg/kg/bw, ZNG was given to rats orally at 25 and 50 mg/kg/bw doses for 14 days. Results: As a result of the presented study, an increase was observed in the MDA contents of the testicular tissue of the rats administered SA, while significant decreases were observed in GSH levels, SOD, CAT, and GPx activities. The mRNA transcript levels of the pro-inflammatory genes NF-κB, TNF-α, IL-1β, and IL-6 were triggered after SA administration. Additionally, SA administration caused inflammation by increasing RAGE, NLRP3, and JAK-2/STAT3 gene expression. Moreover, endoplasmic reticulum (ER) stress occurred in the testicular tissues of SA-treated rats and thus ATF-6, PERK, IRE1, and GRP78 genes were up-regulated. SA caused apoptosis by up-regulating Bax and Caspase-3 expressions and inhibiting Bcl-2 expression in testicles. SA caused histological irregularities in the testicles, resulting in decreased sperm quality. Conclusion: ZNG treatment reduced SA-induced oxidative stress, ER stress, inflammation, apoptosis, and histological irregularities in the testicles while increasing sperm quality. As a result, it was observed that ZNG could alleviate the toxicity caused by SA in the testicles. [ABSTRACT FROM AUTHOR]

The article focuses on evaluating citicoline's protective effect against nephrotoxicity induced by sodium arsenite in mice, it emphasizes the potential role in mitigating oxidative stress and inflammation. It reports that citicoline effectively reduces histopathological damage and restores the balance in oxidative and antioxidant systems in sodium arsenite-exposed mice, and it highlights the therapeutic promise for kidney protection in arsenic toxicity.

Objective(s): In the present study, the potential protective effects of zingerone (ZNG) against sciatic nerve damage caused by sodium arsenite (SA), a common environmental pollutant, were evaluated by various biochemical, molecular, and histological methods. Materials and Methods: In the study, SA and ZNG were given to 35 male Sprague Dawley rats for 14 days. At the end of the period, the sciatic nerve tissues were taken and the markers involved in oxidative stress, endoplasmic reticulum stress, inflammation, and apoptosis were analyzed. Results: The data obtained showed that SA decreased glutathione (GSH) levels and increased malondialdehyde (MDA) levels in the sciatic nerve tissue. However, it was determined that these markers approached the control group levels due to the anti-oxidant properties of ZNG. While SA triggered endoplasmic reticulum stress and apoptosis pathways, ZNG suppressed them. Moreover, SA up-regulated inflammatory markers such as nuclear factor kappa-B (NF-κB), tumor necrosis factoralpha (TNF-α), interleukin-1-beta (IL-1β), and neuronal nitric oxide synthases (nNOS) in the sciatic nerves and caused neuro-inflammation and inhibited cell survival by suppressing serine/threonineprotein kinase 2 (Akt2) and forkhead box protein O1 (FOXO1) genes. It has also been shown histopathologically that SA causes degeneration in the sciatic nerves. In contrast, ZNG suppressed neuro-inflammation, activated Akt2/FOXO1 signaling, and repaired histological irregularities. Conclusion: In general, SA caused oxidative stress, inflammation, ER stress, and apoptosis in the sciatic nerves of rats, causing damage to the tissues, however, ZNG suppressed these pathways and protected the sciatic nerves from the destructive effect of SA. [ABSTRACT FROM AUTHOR]

Arsenic (As) is a metal with potentially toxic effects on different organisms. Hydrogen sulfide (H2S) plays a vital role in mitigating heavy metal toxicity by reducing oxidative stress in plants and animals. However, the role of H2S in alleviating arsenic toxicity in yeast cells remains unclear. In this study, the role of NaHS (exogenous physiological H2S) in alleviating As-induced yeast cell death was investigated. Yeast cells in the logarithmic phase were pretreated with 0.05 mmol/L NaHS for 6 h, and then incubated in the YPD medium with or without 1 mmol/L As. After 12 h of treatment, relative survival rate, H2S content, oxidative stress biomarkers, and antioxidant machinery were measured. Our results showed that sodium arsenite-induced yeast cell death and pretreatment with 0.05 mmol/L NaHS significantly alleviated sodium arsenite-induced cell death. Under sodium arsenite conditions, the levels of intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) increased, accompanied by the inhibition of the catalase (CAT) activity and the downregulation of CTT1 expression. However, the activities of the superoxide dismutase (SOD) and glutathion peroxidase (GPX) increased, and the expression of SOD1 and GPX2 was markedly upregulated in the group treated with sodium arsenite. When yeast cells were pretreated with NaHS, the intracellular ROS and MDA levels decreased significantly, and the activities of SOD, CAT, and GPX increased significantly. This was associated with a significant increase in relative survival rate and H2S content compared to the arsenic treatment alone. Our findings indicate that NaHS alleviates sodium arsenite-induced yeast cell death, mainly by enhancing the antioxidant defense system. [ABSTRACT FROM AUTHOR]

We recently reported that arsenic caused insulin resistance in differentiated human neuroblastoma SH‐SY5Y cells. Herein, we further investigated the effects of sodium arsenite on IGF‐1 signaling, which shares downstream signaling with insulin. A time‐course experiment revealed that sodium arsenite began to decrease IGF‐1‐stimulated Akt phosphorylation on Day 3 after treatment, indicating that prolonged sodium arsenite treatment disrupted the neuronal IGF‐1 response. Additionally, sodium arsenite decreased IGF‐1‐stimulated tyrosine phosphorylation of the IGF‐1 receptor β (IGF‐1Rβ) and its downstream target, insulin receptor substrate 1 (IRS1). These results suggested that sodium arsenite impaired the intrinsic tyrosine kinase activity of IGF‐1Rβ, ultimately resulting in a reduction in tyrosine‐phosphorylated IRS1. Sodium arsenite also reduced IGF‐1 stimulated tyrosine phosphorylation of insulin receptor β (IRβ), indicating the potential inhibition of IGF‐1R/IR crosstalk by sodium arsenite. Interestingly, sodium arsenite also induced neurite shortening at the same concentrations that caused IGF‐1 signaling impairment. A 24‐h IGF‐1 treatment partially rescued neurite shortening caused by sodium arsenite. Moreover, the reduction in Akt phosphorylation by sodium arsenite was attenuated by IGF‐1. Inhibition of PI3K/Akt by LY294002 diminished the protective effects of IGF‐1 against sodium arsenite‐induced neurite retraction. Together, our findings suggested that sodium arsenite‐impaired IGF‐1 signaling, leading to neurite shortening through IGF‐1/PI3K/Akt. [ABSTRACT FROM AUTHOR]

Oligodendrocyte (OL) injury and subsequent loss is a pathologic hallmark of multiple sclerosis (MS). Stress granules (SGs) are membrane-less organelles containing mRNAs stalled in translation and considered as participants of the cellular response to stress. Here we show SGs in OLs in active and inactive areas of MS lesions as well as in normal-appearing white matter. In cultures of primary human adult brain derived OLs, metabolic stress conditions induce transient SG formation in these cells. Combining pro-inflammatory cytokines, which alone do not induce SG formation, with metabolic stress results in persistence of SGs. Unlike sodium arsenite, metabolic stress induced SG formation is not blocked by the integrated stress response inhibitor. Glycolytic inhibition also induces persistent SGs indicating the dependence of SG formation and disassembly on the energetic glycolytic properties of human OLs. We conclude that SG persistence in OLs in MS reflects their response to a combination of metabolic stress and pro-inflammatory conditions. Oligodendrocyte (OL) injury and loss is a pathologic hallmark of multiple sclerosis. Here, the authors show the presence of stress granules in OLs in multiple sclerosis lesions, and their in vitro studies in human OLs indicate that stress granules formation is a response to a combination of metabolic stress and pro-inflammatory conditions. [ABSTRACT FROM AUTHOR]

Viruses evolve many strategies to ensure the efficient synthesis of their proteins. One such strategy is the inhibition of the integrated stress response—the mechanism through which infected cells arrest translation through the phosphorylation of the alpha subunit of the eukaryotic translation initiation factor 2 (eIF2α). We have recently shown that the human common cold betacoronavirus OC43 actively inhibits eIF2α phosphorylation in response to sodium arsenite, a potent inducer of oxidative stress. In this work, we examined the modulation of integrated stress responses by OC43 and demonstrated that the negative feedback regulator of eIF2α phosphorylation GADD34 is strongly induced in infected cells. However, the upregulation of GADD34 expression induced by OC43 was independent from the activation of the integrated stress response and was not required for the inhibition of eIF2α phosphorylation in virus-infected cells. Our work reveals a complex interplay between the common cold coronavirus and the integrated stress response, in which efficient viral protein synthesis is ensured by the inhibition of eIF2α phosphorylation but the GADD34 negative feedback loop is disrupted. [ABSTRACT FROM AUTHOR]

Chia seeds offer therapeutic properties that aid in the prevention of a variety of ailments, including cardiovascular disease, diabetes, obesity, and other risk factors. Arsenite, a common environmental chemical, has been identified as a reproductive toxin owing to its negative effects on male reproductive health. It has been shown to inhibit spermatogenesis and generate androgenic effects in men. The primary goal of this research was to look into the effect of Salvia hispanica on testicular toxicity caused by sodium arsenite in male rats. A set of 36 male albino rats was allocated to a negative control cohort. The individuals in this group were given a basic meal and orally given distilled water for a duration of 28 days. The other five groups were given a regular meal and received intra-peritoneal injections of sodium arsenite (NaAsO2) at a concentration of 4 mg/kg body weight that was diluted in a 0.9% NaCl solution. The injections were administered consecutively, with two doses given within a two-day period. Subsequently, the rats were categorized into several groups using the following classification: Group 2 consisted of a positive control cohort, in which the rats were given a typical baseline diet. Groups 3, 4, 5, and 6 were given a basic diet that included varying proportions of ground chia seeds, namely 5%, 10%, 15%, and 20% per 100 g of the diet. After the trial was completed, the rats were euthanized, and further biological examination was conducted. The measurements of the reproductive organs were documented and reported. The research assessed the following characteristics: sperm count, motility, progressive motility, and normal morphology. The research included examining serum sex hormones, namely luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone. An evaluation of the activity of antioxidant enzymes was performed in the tissue of the testicles. There were statistically significant improvements in the sperm parameters, serum sex hormone levels, and the activity of antioxidant enzymes, such as GPX, SOD, and CAT, in the therapy groups. The levels of malondialdehyde (MDA) exhibited a noteworthy decrease (p ≤ 0.05) when compared to the positive control group. Salvia hispanica seeds have demonstrated a significant level of effectiveness in reducing sodium arsenite-induced testicular toxicity, which leads to the conclusion. The flavonoid content and antioxidant properties of Salvia hispanica seeds may be to blame for the observed behavior. These indicated characteristics may have therapeutic significance in treating testicular harm induced by arsenite exposure. [ABSTRACT FROM AUTHOR]

The compound known as Sodium arsenite (NaAsO2), which is a prevalent type of inorganic arsenic found in the environment, has been strongly associated with liver fibrosis (LF), a key characteristic of nonalcoholic fatty liver disease (NAFLD), which has been demonstrated in our previous study. Our previous research has shown that exposure to NaAsO2 triggers the activation of hepatic stellate cells (HSCs), a crucial event in the development of LF. However, the molecular mechanism is still unknown. N6-methyladenosine (m6A) modification is the most crucial post-transcriptional modification in liver disease. Nevertheless, the precise function of m6A alteration in triggering HSCs and initiating LF caused by NaAsO2 remains unknown. Here, we found that NaAsO2 induced LF and HSCs activation through TGF-β/Smad signaling, which could be reversed by TGF-β1 knockdown. Furthermore, NaAsO2 treatment enhanced the m6A modification level both in vivo and in vitro. Significantly, NaAsO2 promoted the specific interaction of METTL14 and IGF2BP2 with TGF-β1 and enhanced the TGF-β1 mRNA stability. Notably, NaAsO2-induced TGF-β/Smad pathway and HSC-t6 cells activation might be avoided by limiting METTL14/IGF2BP2-mediated m6A modification. Our findings showed that the NaAsO2-induced activation of HSCs and LF is made possible by the METTL14/IGF2BP2-mediated m6A methylation of TGF-β1, which may open up new therapeutic options for LF brought on by environmental hazards.

The metalloid arsenic, known for its toxic properties, is widespread presence in the environment. Our previous research has confirmed that prolonged exposure to arsenic can lead to liver fibrosis injury in rats, while the precise pathogenic mechanism still requires further investigation. In the past few years, the Nod-like receptor protein 3 (NLRP3) inflammasome has been found to play a pivotal role in the occurrence and development of liver injury. In this study, we administered varying doses of sodium arsenite (NaAsO2) and 10 mg/kg.bw MCC950 (a particular tiny molecular inhibitor targeting NLRP3) to Sprague-Dawley (SD) rats for 36 weeks to explore the involvement of NLRP3 inflammasome in NaAsO2-induced liver injury. The findings suggested that prolonged exposure to NaAsO2 resulted in pyroptosis in liver tissue of SD rats, accompanied by the fibrotic injury, extracellular matrix (ECM) deposition and liver dysfunction. Moreover, long-term NaAsO2 exposure activated NLRP3 inflammasome, leading to the release of pro-inflammatory cytokines in liver tissue. After treatment with MCC950, the induction of NLRP3-mediated pyroptosis and release of pro-inflammatory cytokines were significantly attenuated, leading to a decrease in the severity of liver fibrosis and an improvement in liver function. To summarize, those results clearly indicate that hepatic fibrosis and liver dysfunction induced by NaAsO2 occur through the activation of NLRP3 inflammasome-mediated pyroptosis, shedding new light on the potential mechanisms underlying arsenic-induced liver damage.

BackgroundArsenic exposure can lead to liver dysfunction, liver steatosis, hepatitis, liver fibrosis, and other liver injuries, but its mechanism is still unclear and effective treatment methods are lacking.ObjectiveTo investigate the potential intervention effect and associated mechanism of Rosa roxburghii Tratt juice on arsenic-induced liver injury in rats from the perspective of S-adenosylmethionine (SAM) metabolism.MethodsThirty-six Wistar rats were randomly divided into six groups, six rats in each group, half male and half female. The low, medium, and high dose groups of sodium arsenite (NaAsO2) were given 2.5, 5.0, and 10.0 NaAsO2 mg·kg−1 (body weight, thereafter), respectively; the control group was given 10 mL·kg−1 deionized water; the Rosa roxburghii Tratt juice intervention group was given 10 mg·kg−1 NaAsO2 for 4 h and then 10 mL·kg−1 Rosa roxburghii Tratt juice; the Rosa roxburghii Tratt juice control group was given 10 mL·kg−1 Rosa roxburghii Tratt juice by gavage. All rats were gavaged once a day, 6 d per week for 4 months. Histopathological changes of rat liver were observed by hematoxylin-eosin (HE) staining. Total bile acids (TBA) and γ-glutamyl transpeptidase (γ-GT) were detected by enzyme cycle method and rate method, respectively. Ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC-MS) was used to evaluate SAM and S-adenosylhomo cysteine (SAH) in rat liver. Real-time fluorescence quantitative reverse transcriptional PCR (RT-qPCR) was used to detect the mRNA expression levels of the genes of glycine-N-methyltransferase (Gnmt), nicotinamide-N-methyltransferase (Nnmt), and phosphatidylethano-lamine N-mathyltransferase (Pemt).ResultsIn the control group, the liver nuclei were stained clearly, the cytoplasm was stained uniformly, and the liver cords were arranged radially without inflammatory infiltration. In the low, medium, and high dose groups of NaAsO2, hepatic sinusoidal dilation, congestion, and inflammatory infiltration were observed to different degrees. Compared with the control group, TBA in the medium and high dose groups of NaAsO2, and γ-GT in the high dose group of NaAsO2 were significantly increased (P

BackgroundThe accumulation of inorganic arsenic in the liver can lead to liver fibrosis. Solute carrier family 7 member 11 (SLC7A11) and cyclin dependent kinase inhibitor 1A (CDKN1A) are ferroptosis related genes that are abnormally expressed in liver and fibrosis diseases, but their impacts on inorganic arsenic induced liver fibrosis has not been reported yet. ObjectiveTo explore the effect of different doses of sodium arsenite on the migration ability of human hepatic stellate (LX-2) cells and the changes in DNA methylation and expression of SLC7A11 and CDKN1A in LX-2 cell activation induced by sodium arsenite. MethodsLX-2 cells were treated with different doses of sodium arsenite for 24 h. The experiment set up four groups: control group (0 μmol·L−1), low-dose group (5 μmol·L−1), medium-dose group (10 μmol·L−1), and high-dose group (15 μm·L−1). Possible morphological changes of LX-2 cells were observed under an inverted microscope in each group. Cell migration and movement were determined by cell scratch assay. Mitochondrial morphology was observed in the control and the high-dose groups under a transmission electron microscope (TEM). Fe2+ fluorescence intensity was detected with a FerroOrange fluorescence probe. Differentially methylated sites were screened using the Illumina 850 K methylation chip. Ferroptosis related markers (SLC7A11 & CDKN1A) and hepatic stellate cell activation related markers [transforming growth factor-β1 (TGF-β1) and collagen type Ⅲ (Collagen Ⅲ)] were detected by real-time fluorescence quantitative PCR and Western blot. ResultsWith the increase of exposure dose, the cells retracted tentacles and gradually became round, and the healing of cell scratches gradually deteriorated. Destruction of mitochondrial membrane integrity and mitochondrial crista fracture in some cells were observed under a TEM in the high-dose group. Laser confocal microscopy showed that the fluorescence intensity of Fe2+ gradually increased with the increase of exposure dose. The results of methylation chip displayed that compared with the control group, high methylation was found in the high-dose group at the cg22659014 site in the promoter region of SLC7A11, and at the cg17964532 site in the promoter region of CDKN1A. With the increase of exposure dose, the mRNA and protein expression levels of SLC7A11 decreased (P0.05), and its protein expression levels in the low-, medium-, and high-dose groups were higher than that in the control group (P

Objective(s): Sodium arsenite (SA) exposure is toxic to the body. Zingerone (ZNG) is a flavonoid with many biological properties found naturally in honey and plants. This study aimed to determine the effects of ZNG on SA-induced rat lung toxicity.Materials and Methods: Thirty-five male Sprague rats were divided into Control, SA, ZNG, SA+ZNG25, and SA+ZNG50 groups (n=7). SA 10 mg/kg and ZNG were administered at two doses (25 and 50 mg/kg) (orally, 14 days). Analysis of oxidative stress, inflammation damage, apoptosis damage, and autophagic damage markers in lung tissue were determined by biochemical and histological methods. Results: The administration of ZNG reduced oxidative stress by increasing SA-induced decreased antioxidant enzyme activities, increasing Nrf-2, HO-1, and NQO1, and decreasing MDA level. ZNG administration reduced inflammation marker levels. Anti-apoptotic Bcl-2 increased and apoptotic Bax and Caspase-3 decreased with ZNG. ZNG promoted the regression of autophagy by reducing Beclin-1, LC3A, and LC3B levels.Conclusion: Evaluating all data showed that SA caused toxic damage to lung tissue by increasing inflammation, apoptosis, autophagy, and oxidant levels, whereas ZNG had a protective effect by reducing this damage.

Long-term exposure to arsenic has been linked to a variety of cancers, among which skin cancer is the most prevalent form. However, the mechanism underlying arsenic carcinogenesis is unclear, and there is still limited information on the role of miRNAs in arsenic-induced skin cancer. This study aims to explore the role of miR-96-5p in the arsenite-induced proliferation and malignant transformation of human HaCaT keratinocytes. The GEO database (accession numbers GSE97303, GSE97305, and GSE97306) was used to extract mRNA and miRNA expression profiles of HaCaT cells treated with or without 0.1 μmol/L sodium arsenite for 3 and 7 weeks. In this paper, according to the CCK8 assay result, HaCaT cells exposed to 0.1 μmol/L sodium arsenite for 48 h were finalized. CCK8, MTT, EdU incorporation, and colony formation assays were used to determine the viability and proliferation of HaCaT cells and transformed HaCaT (T-HaCaT) cells. The subcellular localization and relative expression levels of DTL, as well as miR-96-5p in HaCaT cells induced by arsenite, were determined via immunofluorescence, RT-qPCR, and Western blot. Dual-luciferase reporter assay was performed to identify miR-96-5p bound directly to DTL. Transfection of miR-96-5p mimics or DTL siRNA was conducted to verify the arsenite-induced viability of HaCaT cells and T-HaCaT cells. T-HaCaT cells and nude mice were used to construct arsenite-induced malignant transformation and an in vivo xenograft model to demonstrate the over-expressed effect of miR-96-5p. The results showed that DTL was the target gene of miR-96-5p. Meanwhile, we also found that 0.1 μmol/L sodium arsenite upregulated DTL by decreasing the miR-96-5p level, leading to the proliferation and malignant transformation of HaCaT cells. MiR-96-5p agomir treatment slowed the growth of transplanted HaCaT cells transformed by arsenite in a manner associated with DTL downregulation in the nude mice xenograft model. Taken together, we confirmed that miR-96-5p, as a potent regulator of DTL, suppressed arsenite-induced HaCaT cell proliferation and malignant transformation, which might provide a novel therapeutic target for the treatment of arsenic-induced skin cancer. [ABSTRACT FROM AUTHOR]

Acute cellular stress is known to induce a global reduction in mRNA translation through suppression of cap dependent translation. Selective translation in response to acute stress has been shown to play important roles in regulating the stress response. However, accurately profiling translational changes transcriptome-wide in response to acute cellular stress has been challenging. Commonly used data normalization methods operate on the assumption that any systematic shifts are experimental artifacts. Consequently, if applied to profiling acute cellular stress-induced mRNA translation changes, these methods are expected to produce biased estimates. To address this issue, we designed, produced, and evaluated a panel of 16 oligomers to serve as external standards for ribosome profiling studies. Using Sodium Arsenite treatment-induced oxidative stress in lymphoblastoid cell lines as a model system, we applied spike-in oligomers as external standards. We found our spike-in oligomers to display a strong linear correlation between the observed and the expected quantification, with small ratio compression at the lower concentration range. Using the expected fold changes constructed from spike-in controls, we found in our dataset that TMM normalization, a popular global scaling normalization approach, produced 87.5% false positives at a significant cutoff that is expected to produce only 10% false positive discoveries. In addition, TMM normalization produced a systematic shift of fold change by 3.25 fold. These results highlight the consequences of applying global scaling approaches to conditions that clearly violate their key assumptions. In contrast, we found RUVg normalization using spike-in oligomers as control genes recapitulated the expected stress induced global reduction of translation and resulted in little, if any, systematic shifts in the expected fold change. Our results clearly demonstrated the utility of our spike-in oligomers, both for constructing expected results as controls and for data normalization. [ABSTRACT FROM AUTHOR]

In response to stress stimuli, eukaryotic cells typically suppress protein synthesis. This leads to the release of mRNAs from polysomes, their condensation with RNA-binding proteins, and the formation of non-membrane-bound cytoplasmic compartments called stress granules (SGs). SGs contain 40S but generally lack 60S ribosomal subunits. It is known that cycloheximide, emetine, and anisomycin, the ribosome inhibitors that block the progression of 80S ribosomes along mRNA and stabilize polysomes, prevent SG assembly. Conversely, puromycin, which induces premature termination, releases mRNA from polysomes and stimulates the formation of SGs. The same effect is caused by some translation initiation inhibitors, which lead to polysome disassembly and the accumulation of mRNAs in the form of stalled 48S preinitiation complexes. Based on these and other data, it is believed that the trigger for SG formation is the presence of mRNA with extended ribosome-free segments, which tend to form condensates in the cell. In this study, we evaluated the ability of various small-molecule translation inhibitors to block or stimulate the assembly of SGs under conditions of severe oxidative stress induced by sodium arsenite. Contrary to expectations, we found that ribosome-targeting elongation inhibitors of a specific type, which arrest solitary 80S ribosomes at the beginning of the mRNA coding regions but do not interfere with all subsequent ribosomes in completing translation and leaving the transcripts (such as harringtonine, lactimidomycin, or T-2 toxin), completely prevent the formation of arsenite-induced SGs. These observations suggest that the presence of even a single 80S ribosome on mRNA is sufficient to prevent its recruitment into SGs, and the presence of extended ribosome-free regions of mRNA is not sufficient for SG formation. We propose that mRNA entry into SGs may be mediated by specific contacts between RNA-binding proteins and those regions on 40S subunits that remain inaccessible when ribosomes are associated. [ABSTRACT FROM AUTHOR]

Astrocytes and microglia, the most abundant glial cells in the central nervous system, are involved in maintaining homeostasis in the brain microenvironment and in the progression of various neurological disorders. Lipocalin-2 (LCN2) is a small secretory protein that can be transcriptionally upregulated via nuclear factor kappa B (NF-κB) signaling. It is synthesized and secreted by glial cells, resulting in either the restoration of damaged neural tissues or the induction of neuronal apoptosis in a context-dependent manner. It has recently been reported that when glial cells are under lipopolysaccharide-induced inflammatory stress, either reduced production or accelerated degradation of LCN2 can alleviate neurotoxicity. However, the regulatory mechanisms of LCN2 in glial cells are not yet fully understood. In this study, we used primary astroglial-enriched cells which produce LCN2 and found that the production of LCN2 could be reduced by sodium arsenite treatment. Surprisingly, the reduced LCN2 production was not due to the suppression of NF-κB signaling. Mild oxidative stress induced by sodium arsenite treatment activated antioxidant responses and downregulated Lcn2 expression without reducing the viability of astroglial-enriched cells. Intriguingly, reduced LCN2 production could not be achieved by simple activation of the nuclear factor erythroid-2-related factor 2 (Nrf2)–Kelch-like ECH-associated protein 1 (Keap1) pathway in astroglial-enriched cells. Thus, it appears that mild oxidative stress, occurring in an Nrf2-independent manner, is required for the downregulation of Lcn2 expression. Taken together, our findings provide new insights into the regulatory mechanisms of LCN2 and suggest that mild oxidative stress may alter LCN2 homeostasis, even under neuroinflammatory conditions. [ABSTRACT FROM AUTHOR]

Arsenic is a carcinogenic metalloid toxicant widely found in the natural environment. Acute or prolonged exposure to arsenic causes a series of damages to the organs, mainly the liver, such as hepatomegaly, liver fibrosis, cirrhosis, and even hepatocellular carcinoma. Therefore, it is imperative to seek drugs to prevent arsenic-induced liver injury. Quinazolines are a class of nitrogen heterocyclic compounds with biological and pharmacological effects in vivo and in vitro. This study was designed to investigate the ameliorating effects of quinazoline derivatives on arsenic-induced liver injury and its molecular mechanism. We investigated the mechanism of the quinazoline derivative KZL-047 in preventing and ameliorating arsenic-induced liver injury in vitro by cell cycle and apoptosis. We performed real-time fluorescence quantitative polymerase chain reaction (qPCR) and Western blotting combined with molecular docking. In vivo, the experiments were performed to investigate the mechanism of KZL-047 in preventing and ameliorating arsenic-induced liver injury using arsenic-infected mice. Physiological and biochemical indices of liver function in mouse serum were measured, histopathological changes in liver tissue were observed, and immunohistochemical staining was used to detect changes in the expression of RecQ-family helicases in mouse liver tissue. The results of in vitro experiments showed that sodium arsenite (SA) inhibited the proliferation of L-02 cells, induced apoptosis, blocked the cell cycle at the G1 phase, and decreased the expression of RecQ family helicase; after KZL-047 treatment in arsenic-induced L-02 cells, the expression of RecQ family helicase was upregulated, and the apoptosis rate was slowed, leading to the restoration of the cell viability level. KZL-047 inhibited arsenic-induced oxidative stress, alleviated oxidative damage and lipid peroxidation in vivo, and ameliorated arsenic toxicity-induced liver injury. KZL-047 restored the expression of RecQ family helicase proteins, which is consistent with the results of in vitro studies. In summary, KZL-047 can be considered a potential candidate for the treatment of arsenic-induced liver injury. [ABSTRACT FROM AUTHOR]

Alphavirus infections cause multiple alterations in the intracellular environment that can have both positive and negative effects on viral replication. The Old World alphaviruses, such as Sindbis (SINV), chikungunya (CHIKV), and Semliki Forest viruses, hinder the ability of vertebrate cells to form stress granules (SGs). Previously, this inhibitory function was attributed to the hypervariable domain (HVD) of nsP3, which sequesters the key SG components, G3BP1 and G3BP2, and to the nsP3 macro domain. The macro domain possesses ADP-ribosylhydrolase activity, which can diminish the ADP-ribosylation of G3BP1 during viral replication. However, our recent findings do not support the prevailing notions. We demonstrate that the interactions between SINV- or CHIKV-specific nsP3s and G3BPs, and the ADP-ribosylhydrolase activity are not major contributors to the inhibitory process, at least when nsP3 is expressed at biologically relevant levels. Instead, the primary factors responsible for suppressing SG formation are virus-induced transcriptional and translational shutoffs that rapidly develop within the first few hours post infection. Poorly replicating SINV variants carrying mutated nsP3 HVD still inhibit SG development even in the presence of sodium arsenite (NaAs). Conversely, SINV mutants lacking transcription and/or translation inhibitory functions lose their ability to inhibit SG formation, despite expressing high levels of wt nsP3. Moreover, we found that stable cell lines expressing GFP-nsP3 fusions retain the capacity to form SGs when exposed to NaAs. However, our results do not rule out the possibility that additional alphavirus-induced changes in cell biology may contribute to the suppression of SG formation. [ABSTRACT FROM AUTHOR]

The Heart and kidney are adversely affected by arsenic toxicity, a highly toxic environmental pollutant. The aim of this study was to evaluate cardio-renal protective effects of taurine against sodium arsenite–induced toxicity. Taurine (2-amino ethane sulphonic acid; TAU) is a major free intracellular amino acid in many mammalian tissues including the liver. Taurine supplementation has been documented to mitigate steatosis and hepatotoxicity in several animal models. Sixty cockerel chicks (1-day old) of uniform weight were randomly assigned into six groups of ten cockerel chicks: Group A, Control; Group B, Sodium arsenite (SA) 75 mg/kg body weight; Group C, SA + 100 mg/kg taurine; Group D, SA + 200 mg/kg taurine; Group E, 100 mg/kg taurine and Group F, 200 mg/kg taurine. At the end of the experiment, blood pressure, electrocardiogram, electrolytes, and kidney function tests together with immunohistochemistry of cardiac troponin, gelatinase-associated lipocalin (NGAL), and podocin were assessed. Our findings revealed significant (P < 0.05) increases in blood pressure parameters, pulse rate, serum electrolytes (sodium, potassium, chloride, and bicarbonate) and markers of oxidative stress, prolonged QTc and PR interval with concurrent significant decrease in antioxidant status of cockerels intoxicated with SA. Immunohistochemistry revealed higher expressions of cardiac troponin, renal NGAL, and podocin in SA-intoxicated chicks relative to control and taurine-treated chicks. Our study shows that taurine supplementation improved the electrolytes and electrocardiographic changes, attenuated oxidative stress biomarkers, high blood pressure, and lowered cardiac troponin, renal NGAL and podocin immuno-reactivity. [ABSTRACT FROM AUTHOR]

Arsenic exposure is a public health concern worldwide. Skin damage, as a typical lesion of arsenic exposure, the mechanism is still unknown. Studies have found that cellular senescence plays a key role in arsenic-induced skin damage, and the previous research found that the ERK/CEBPB signaling pathway may be an important molecular event of arsenic-induced skin cell senescence, but its specific mechanism is unknown. In this study, genetic engineering technology was used to construct stable HaCaT cell lines, and the role and mechanism of ERK/CEBPB signaling pathway in arsenic-induced HaCaT cell senescence were verified by knockdown and overexpression of ERK and CEBPB in both forward and backward. It was found that knockdown of CEBPB or ERK can downregulate the ERK/CEBPB signaling pathway and reduce arsenic-induced skin cell senescence. In contrast to knockdown, overexpression of CEBPB or ERK can upregulate the ERK/CEBPB signaling pathway and aggravate the senescence of skin cells caused by arsenic. These findings suggest that sodium arsenite can further promote SASP secretion and the expression of p53, p21 and p16 INK4a by activating the ERK/CEBPB signaling pathway, induce cell cycle arrest and trigger cellular senescence. [ABSTRACT FROM AUTHOR]

Arsenic being a toxic metalloid ubiquitously persists in environment and causes several health complications including female reproductive anomalies. Epidemiological studies documented birth anomalies due to arsenic exposure. Augmented reactive oxygen species (ROS) generation and quenched antioxidant pool are foremost consequences of arsenic threat. On the contrary, Vitamin E (VE) and C (VC) are persuasive antioxidants and conventionally used in toxicity management. Present study was designed to explore the extent of efficacy of combined VE and VC (VEC) against Sodium arsenite (NaAsO2) mediated ovarian damage. Thirty-six female Wistar rats were randomly divided into three groups (Grs) and treated for consecutive 30 days; Gr I (control) was vehicle fed, Gr II (treated) was gavaged with NaAsO2 (3 mg/kg/day), Gr III (supplement) was provided with VE (400 mg/kg/day) & VC (200 mg/kg/day) along with NaAsO2. Marked histological alterations were evidenced by disorganization in oocyte, granulosa cells and zona pellucida layers in treated group. Considerable reduction of different growing follicles along with increased atretic follicles was noted in treated group. Altered activities ofΔ5 3β-Hydroxysteroid dehydrogenase and 17β-Hydroxysteroid dehydrogenase accompanied by reduced luteinizing hormone, follicle-stimulating hormone and estradiol levels were observed in treated animals. Irregular estrous cyclicity pattern was also observed due to NaAsO2 threat. Surplus ROS production affected ovarian antioxidant strata as evidenced by altered oxidative stress markers. Provoked oxidative strain further affects DNA status of ovary. However, supplementation with VEC caused notable restoration from such disparaging effects of NaAsO2 toxicities. Antioxidant and antiapoptotic attributes of those vitamins might be liable for such restoration. [ABSTRACT FROM AUTHOR]

BACKGROUND: Vascular endothelial cells are the main target of arsenic toxicity and the molecular mechanism of arsenic-induced endothelial cell injury needsto be further studied. OBJECTIVE: To study the effects of sodium arsenite on human umbilical vein endothelial cell injury and sphingosine kinase 1/sphingosine 1-phosphate signaling axis of human umbilical vein endothelial cells. METHODS: Human umbilical vein endothelial cells were isolated, cultured, and identified. The cells were treated with 0, 5, 10, 15, 20, 25 µmol/L sodium arsenite for 24 hours. Cell viability was detected by cell counting kit-8. Cell morphology was observed by inverted phase contrast microscope. The content of intracellular reactive oxygen species was detected by fluorescent probe DCFH-DA. Annexin V-FITC/PI double labeling combined with flow cytometry and TUNEL were used to detect apoptosis. The content of sphingosine 1-phosphate in cells was detected by ELISA. The mRNA and protein expressions of vascular cell adhesion molecule-1, sphingosine kinase 1, and sphingosine 1-phosphate were detected by real-time fluorescence quantitative PCR and western blot respectively. RESULTS AND CONCLUSION: Compared with the control group (0 µmol/L sodium arsenite), the cell viability decreased gradually along with the increased concentration of sodium arsenite in a dose-dependent manner; the cell fusion rate decreased gradually, the cell gap widened gradually, and the number of exfoliated and floating cells increased gradually; the reactive oxygen species content and apoptosis rate increased gradually; the sphingosine 1-phosphate content in cells increased gradually; the relative mRNA and protein expressions of vascular cell adhesion molecule-1 and sphingosine kinase 1 increased gradually, but the relative mRNA and protein expression of sphingosine kinase 1 decreased gradually. To conclude, sodium arsenite-injured human umbilical vein endothelial cell injury may be related to the activation of sphingosine kinase 1/sphingosine 1-phosphate signaling axis and the downregulation of sphingosine 1-phosphate receptor 1. Sphingosine kinase 1/sphingosine 1-phosphate signaling axis may become a new target of arsenic-induced cardiovascular injury. [ABSTRACT FROM AUTHOR]

Objective To observe the effect of sodium arsenite (NaAsO2) on the activation of human hepatic stellate cells and its relationship with ferroptosis. Methods Human liver stellate cells LX-2 were cultured in vitro, and were divided in the NaAsO2 group and control group. Cells in the NaAsO2 group were treated with 5, 10 and 15 µmol/L NaAsO2 for 24 h, respectively, and cells in the control group underwent normal culture. The morphological changes of cells were observed under inverted microscope. The content of glutathione (GSH) was determined by colorimetry. Fluorescent probe was used to detect cell lipid reactive oxygen species (ROS). Ferroptosis markers SLC7A11 and glutathione peroxidase 4 (GPX4), fibrosis markers α smooth muscle actin (α-SMA) and CollagenⅠmRNA were detected by RT-PCR. Spearman correlation analysis was used to analyze the correlation between fibrosis index and ferroptosis index. Results With the in‑ crease of NaAsO2 concentration, the cell antennae gradually retreated, the number of cells decreased, and the intercellular space expanded. Compared with the control group, the GSH content of cells in different NaAsO2 concentration groups decreased, and the GSH content in the 15µmol/L NaAsO2 group was lower than that in the 10 and 5 µmol/L NaAsO2 groups, and that in the 10 µmol/L NaAsO2 group was lower than that in the 5 µmol/L NaAsO2 group (all P<0. 05). Compared with the control group, the fluorescence intensity of lipid ROS in the NaAsO2 groups was enhanced. Compared with the control group, α-SMA and Collagen1 mRNA expression levels in the 5, 10 and 15 µmol/L NaAsO2 groups increased, and those in the 15 µmol/L NaAsO2 group were higher than those in the 10 and 5 µmol/L NaAsO2 groups; those in the 10 µmol/L Na‑ AsO2 group were higher than those in the 5 µmol/L NaAsO2 group (all P<0. 05). Compared with the control group, the mRNA expression levels of SLC7A11 and GPX4 in the 5, 10 and 15 µmol/L NaAsO2 groups decreased, and those in the 15 µmol/L NaAsO2 group were lower than those in the 10 and 5 µmol/L NaAsO2 groups; those in the 10 µmol/L NaAsO2 group were lower than those in the 5 µmol/L NaAsO2 group. The α-SMA mRNA was negatively correlated with GPX4 and SLC7A11 mRNA expression (r=-0. 72, -0. 92, respectively; both P<0. 01), and CollagenⅠ mRNA was negatively correlated with GPX4 and SLC7A11 mRNA expression (r=-0. 67, -0. 90, respectively; both P<0. 01). Conclusions With the increase of NaAsO2 concentration, the expression level of fibrosis gene increases gradually, which causes the activation of hepatic stellate cells. In this process, the down-regulated expression of SLC7A11 and GPX4 genes causes ROS accumulation and promotes ferroptosis in hepatic stellate cells. [ABSTRACT FROM AUTHOR]

Objective(s): Sodium arsenite (SA) exposure is toxic to the body. Zingerone (ZNG) is a flavonoid with many biological properties found naturally in honey and plants. This study aimed to determine the effects of ZNG on SA-induced rat lung toxicity. Materials and Methods: Thirty-five male Sprague rats were divided into Control, SA, ZNG, SA+ZNG25, and SA+ZNG50 groups (n=7). SA 10 mg/kg and ZNG were administered at two doses (25 and 50 mg/kg) (orally, 14 days). Analysis of oxidative stress, inflammation damage, apoptosis damage, and autophagic damage markers in lung tissue were determined by biochemical and histological methods. Results: The administration of ZNG reduced oxidative stress by increasing SA-induced decreased antioxidant enzyme activities, increasing Nrf-2, HO-1, and NQO1, and decreasing MDA level. ZNG administration reduced inflammation marker levels. Anti-apoptotic Bcl-2 increased and apoptotic Bax and Caspase-3 decreased with ZNG. ZNG promoted the regression of autophagy by reducing Beclin-1, LC3A, and LC3B levels. Conclusion: Evaluating all data showed that SA caused toxic damage to lung tissue by increasing inflammation, apoptosis, autophagy, and oxidant levels, whereas ZNG had a protective effect by reducing this damage. [ABSTRACT FROM AUTHOR]

Introduction: Arsenic poisoning in the groundwater in recent times has become a major problem in the entire world. The exposed subjects exhibit typical symptoms of arsenicosis such as skin manifestations, gastrointestinal disorders, neurological disorders, hormonal disorders etc. Objective: The present study is focused to combat the deleterious effect of arsenic toxicity in animal models using honey. Materials and Methods: The animals (Charles Foster rats) were treated with Sodium arsenite at the dose of 8 mg per Kg body weight for 90 days to make arsenic model and upon these arsenic pre-treated rats honey at the dose of 200 mg per Kg body weight (1:1) was administered for 60 days to study the antidote effects. After the entire treatment, rats were sacrificed and their blood samples were obtained and analysed for haematological and biochemical and histopathological study. Results: The study shows that arsenic induced toxicity caused severe damage to the rats at the haematological level such as decrease in the RBC counts, WBC counts, haemoglobin percentage, and biochemical level such as increase in the levels of SGPT, SGOT, ALP, bilirubin, urea, uric acid, creatinine, and lipid peroxidation. There was also high magnitude of degeneration observed at the histopathological level in the liver and kidney tissues. But, there was significant normalization in the honey on arsenic pretreated group of rats at all the respective studied parameters. Conclusion: The studied parameters denote that honey possesses antidote properties against arsenic induced toxicity and can be used for human purpose after dose titration as antidote. [ABSTRACT FROM AUTHOR]

The inadvertent exposure to environmental contaminants has been reported to induce cancer in different animal models. Here, we investigated the toxicity of Sodium Arsenite (SA), a Class I Carcinogen in Drosophila melanogaster. Harwich fly strain (1–3 days old) of both sexes were orally exposed to SA (0, 0.0312, 0.0625 and 0.125 mM) for 14 days for survival study. Thereafter, 5 days exposure period was selected to assess the toxic effects of SA on oxidative stress and antioxidant markers. The results indicated that SA induced significant reduction in survival and emergence rate of flies. Furthermore, SA significantly increased Nitric Oxide (NO, nitrite and nitrate) and Hydrogen Peroxide (H2O2) levels in flies compared with control (p<0.05). In addition, SA inhibited catalase and glutathione-S-transferase (GST) activities, and depleted total thiol and glutathione (GSH) contents. Moreover, acetylcholinesterase activity significantly increased in flies treated with SA when compared with control. Sodium arsenite-induced reduction in survival and emergence rates of flies occurred via the disruption of oxidative stress-antioxidant homeostasis in D. melanogaster. [ABSTRACT FROM AUTHOR]

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]