Pub Date : 2022-06-21DOI: 10.1080/15376516.2022.2087049
Khawla Ezdini, Jalila Ben Salah-Abbès, Hela Belgacem, Bolanle Ojokoh, Kamel Chaieb, Samir Abbès
Fumonisin B1 (FB1) is a possible carcinogenic molecule for humans as classified by the International Agency for Research on Cancer (IARC) in 2B group. In livestock, it is responsible for several mycotoxicoses and economic losses. Lactobacillus strains, inhabitants of a wide range of foodstuffs and the gastrointestinal tract, are generally recognized as safe (GRAS). Thus, the aim of this work was to evaluate the protective effect of Lactobacillus paracasei (LP) against FB1-induced reprotoxicities including testicular histopathology, sperm quality disturbance, and testosterone level reduction.Pubescent mice were divided randomly into four groups and treated for 10 days. Group 1: Control; Group 2: FB1 (100 μg/kg b.w); Group 3: LP (2 × 109 CFU/kg b.w); Group 4: LP (2 × 109 CFU/kg b.w) and FB1 (100 μg/kg b.w). After the end of the treatment, animals were sacrificed. Plasma, epididymis, and testis were collected for reproductive system studies.Our results showed that FB1 altered epididymal sperm quality, generated oxidative stress, and induced histological alterations. Interestingly, these deleterious effects have been counteracted by the LP administration in mice.In conclusion, LP was able to prevent FB1-reproductive system damage in BALB/c mice and could be validated as an anti-caking agent in an animal FB1-contaminated diet.
{"title":"The ameliorative effect of <i>Lactobacillus paracasei</i> BEJ01 against FB1 induced spermatogenesis disturbance, testicular oxidative stress and histopathological damage.","authors":"Khawla Ezdini, Jalila Ben Salah-Abbès, Hela Belgacem, Bolanle Ojokoh, Kamel Chaieb, Samir Abbès","doi":"10.1080/15376516.2022.2087049","DOIUrl":"10.1080/15376516.2022.2087049","url":null,"abstract":"<p><p>Fumonisin B1 (FB1) is a possible carcinogenic molecule for humans as classified by the International Agency for Research on Cancer (IARC) in 2B group. In livestock, it is responsible for several mycotoxicoses and economic losses. <i>Lactobacillus</i> strains, inhabitants of a wide range of foodstuffs and the gastrointestinal tract, are generally recognized as safe (GRAS). Thus, the aim of this work was to evaluate the protective effect of <i>Lactobacillus paracasei</i> (LP) against FB1-induced reprotoxicities including testicular histopathology, sperm quality disturbance, and testosterone level reduction.Pubescent mice were divided randomly into four groups and treated for 10 days. Group 1: Control; Group 2: FB1 (100 μg/kg b.w); Group 3: LP (2 × 10<sup>9</sup> CFU/kg b.w); Group 4: LP (2 × 10<sup>9</sup> CFU/kg b.w) and FB1 (100 μg/kg b.w). After the end of the treatment, animals were sacrificed. Plasma, epididymis, and testis were collected for reproductive system studies.Our results showed that FB1 altered epididymal sperm quality, generated oxidative stress, and induced histological alterations. Interestingly, these deleterious effects have been counteracted by the LP administration in mice.In conclusion, LP was able to prevent FB1-reproductive system damage in BALB/c mice and could be validated as an anti-caking agent in an animal FB1-contaminated diet.</p>","PeriodicalId":49117,"journal":{"name":"Toxicology Mechanisms and Methods","volume":"33 1","pages":"1-10"},"PeriodicalIF":3.2,"publicationDate":"2022-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49425965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-13DOI: 10.1038/s41597-022-01299-1
Xingyu Liu, Yuxuan Dai, Hailun Xie, Zonglei Zhen
Naturalistic stimuli, such as movies, are being increasingly used to map brain function because of their high ecological validity. The pioneering studyforrest and other naturalistic neuroimaging projects have provided free access to multiple movie-watching functional magnetic resonance imaging (fMRI) datasets to prompt the community for naturalistic experimental paradigms. However, sluggish blood-oxygenation-level-dependent fMRI signals are incapable of resolving neuronal activity with the temporal resolution at which it unfolds. Instead, magnetoencephalography (MEG) measures changes in the magnetic field produced by neuronal activity and is able to capture rich dynamics of the brain at the millisecond level while watching naturalistic movies. Herein, we present the first public prolonged MEG dataset collected from 11 participants while watching the 2 h long audio-visual movie "Forrest Gump". Minimally preprocessed data was also provided to facilitate the use of the dataset. As a studyforrest extension, we envision that this dataset, together with fMRI data from the studyforrest project, will serve as a foundation for exploring the neural dynamics of various cognitive functions in real-world contexts.
{"title":"A studyforrest extension, MEG recordings while watching the audio-visual movie \"Forrest Gump\".","authors":"Xingyu Liu, Yuxuan Dai, Hailun Xie, Zonglei Zhen","doi":"10.1038/s41597-022-01299-1","DOIUrl":"10.1038/s41597-022-01299-1","url":null,"abstract":"<p><p>Naturalistic stimuli, such as movies, are being increasingly used to map brain function because of their high ecological validity. The pioneering studyforrest and other naturalistic neuroimaging projects have provided free access to multiple movie-watching functional magnetic resonance imaging (fMRI) datasets to prompt the community for naturalistic experimental paradigms. However, sluggish blood-oxygenation-level-dependent fMRI signals are incapable of resolving neuronal activity with the temporal resolution at which it unfolds. Instead, magnetoencephalography (MEG) measures changes in the magnetic field produced by neuronal activity and is able to capture rich dynamics of the brain at the millisecond level while watching naturalistic movies. Herein, we present the first public prolonged MEG dataset collected from 11 participants while watching the 2 h long audio-visual movie \"Forrest Gump\". Minimally preprocessed data was also provided to facilitate the use of the dataset. As a studyforrest extension, we envision that this dataset, together with fMRI data from the studyforrest project, will serve as a foundation for exploring the neural dynamics of various cognitive functions in real-world contexts.</p>","PeriodicalId":49117,"journal":{"name":"Toxicology Mechanisms and Methods","volume":"27 1","pages":"206"},"PeriodicalIF":5.8,"publicationDate":"2022-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9106652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"57531406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-11DOI: 10.1080/15376516.2022.2076635
Y. Shiojima, N. Deshmukh, H. Moriyama, Yogini Soman, Prashant Nalge, Manisha Randhe, Jaideep Kanhere, Aasavari Karmarkar, M. Bagchi, D. Bagchi
Abstract Pyrroloquinoline quinone (PQQ), a potent coenzyme antioxidant naturally occurring in foods, has been demonstrated to protect brain cells by enhancing the expression of nerve growth factors (NGF) and NGF receptors, and suppressing the fibril formation and aggression of amyloid β. We developed mnemoPQQ®, a novel PQQ disodium salt and assessed its safety in GLP compliant toxicity studies. Acute toxicity studies of mnemoPQQ® in Wistar rats revealed that its LD50 was 1825- and 1410 mg/kg body weight (bw) in male and female rats, respectively, whereas its acute dermal LD50 was >2000 mg/kg bw. mnemoPQQ® was found to be nonirritant to the skin of rabbit in an acute dermal irritation/corrosion study, and classified mnemoPQQ® as a nonirritant to the eye of rabbit in an acute eye irritation/corrosion study. Ames bacterial reverse mutation assay and in vitro Mammalian cell gene mutation test exhibited its non-mutagenic potential. In mammalian in vivo erythrocyte micronucleus test, mnemoPQQ® was classified as non-clastogenic and non-mutagenic. A 90-day sub-chronic toxicity study, conducted at and up to the highest daily dose of 600 mg/kg body weight, revealed no evidence of systemic toxicity. All rats survived the treatment without any significant abnormal clinical signs and alterations in hematology, clinical chemistry, neurological evaluation, thyroid functions, reproductive hormone levels, sperm evaluations, vaginal cytology, endocrine functions, organ weight and gross and microscopic pathology findings. No observed adverse effect level (NOAEL) of mnemoPQQ® was found to be greater than 600 mg/kg body weight. These studies affirm that mnemoPQQ® has broad spectrum safety for human consumption.
{"title":"Safety assessment of a novel, dietary pyrroloquinoline quinone disodium salt (mnemoPQQ®)","authors":"Y. Shiojima, N. Deshmukh, H. Moriyama, Yogini Soman, Prashant Nalge, Manisha Randhe, Jaideep Kanhere, Aasavari Karmarkar, M. Bagchi, D. Bagchi","doi":"10.1080/15376516.2022.2076635","DOIUrl":"https://doi.org/10.1080/15376516.2022.2076635","url":null,"abstract":"Abstract Pyrroloquinoline quinone (PQQ), a potent coenzyme antioxidant naturally occurring in foods, has been demonstrated to protect brain cells by enhancing the expression of nerve growth factors (NGF) and NGF receptors, and suppressing the fibril formation and aggression of amyloid β. We developed mnemoPQQ®, a novel PQQ disodium salt and assessed its safety in GLP compliant toxicity studies. Acute toxicity studies of mnemoPQQ® in Wistar rats revealed that its LD50 was 1825- and 1410 mg/kg body weight (bw) in male and female rats, respectively, whereas its acute dermal LD50 was >2000 mg/kg bw. mnemoPQQ® was found to be nonirritant to the skin of rabbit in an acute dermal irritation/corrosion study, and classified mnemoPQQ® as a nonirritant to the eye of rabbit in an acute eye irritation/corrosion study. Ames bacterial reverse mutation assay and in vitro Mammalian cell gene mutation test exhibited its non-mutagenic potential. In mammalian in vivo erythrocyte micronucleus test, mnemoPQQ® was classified as non-clastogenic and non-mutagenic. A 90-day sub-chronic toxicity study, conducted at and up to the highest daily dose of 600 mg/kg body weight, revealed no evidence of systemic toxicity. All rats survived the treatment without any significant abnormal clinical signs and alterations in hematology, clinical chemistry, neurological evaluation, thyroid functions, reproductive hormone levels, sperm evaluations, vaginal cytology, endocrine functions, organ weight and gross and microscopic pathology findings. No observed adverse effect level (NOAEL) of mnemoPQQ® was found to be greater than 600 mg/kg body weight. These studies affirm that mnemoPQQ® has broad spectrum safety for human consumption.","PeriodicalId":49117,"journal":{"name":"Toxicology Mechanisms and Methods","volume":"32 1","pages":"662 - 677"},"PeriodicalIF":3.2,"publicationDate":"2022-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47178796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-12DOI: 10.1080/15376516.2022.2065225
R. L. Shyma, S. Mini
Abstract Long-term diabetes mellitus results in neuronal damage by increased intracellular glucose leading to oxidative stress. This condition is known as diabetic encephalopathy. Morin is a bioflavonoid, has significant antidiabetic, antioxidant and anti-inflammatory activities. The present study investigated whether the antioxidant properties of morin has beneficial effects on structural brain damage, neuronal apoptosis and dysregulation of TrkB/Akt signaling associated with diabetes. Adult male Sprague Dawley rats were induced diabetes by an intraperitoneal injection of 40 mg/kg of streptozotocin and kept untreated for 30 days to induce DE. Cognitive performance was assessed using the Morris water maze test followed by morin and metformin administration at the doses of 50 and 100 mg/kg, respectively, for 60 days. After 60 days of treatment, animals were subjected to the behavioral test and sacrificed to collect blood and brain and checked biochemical parameters. The treatment with morin could significantly reduce the escape latency time in Morris water maze test, blood glucose level, HbA1c, toxicity markers, lipid peroxidation products and protein carbonyl content, downregulated the expression of Bax, Caspase - 3 and Cytochrome C and upregulated Bcl-2, Bcl-XL, Akt, BDNF and TrkB expressions. Besides, enhanced the activities of antioxidant enzymes, and plasma insulin level. Histomorphological observations also confirmed the protective effect of morin on neuronal degeneration. Morin 50 mg once daily for 60 days was the most effective dose with a significant reduction in diabetes mediated complications in the brain associated with neuronal apoptosis and dysregulation of TrkB/Akt signaling.
{"title":"Neuroprotective effect of Morin via TrkB/Akt pathway against diabetes mediated oxidative stress and apoptosis in neuronal cells","authors":"R. L. Shyma, S. Mini","doi":"10.1080/15376516.2022.2065225","DOIUrl":"https://doi.org/10.1080/15376516.2022.2065225","url":null,"abstract":"Abstract Long-term diabetes mellitus results in neuronal damage by increased intracellular glucose leading to oxidative stress. This condition is known as diabetic encephalopathy. Morin is a bioflavonoid, has significant antidiabetic, antioxidant and anti-inflammatory activities. The present study investigated whether the antioxidant properties of morin has beneficial effects on structural brain damage, neuronal apoptosis and dysregulation of TrkB/Akt signaling associated with diabetes. Adult male Sprague Dawley rats were induced diabetes by an intraperitoneal injection of 40 mg/kg of streptozotocin and kept untreated for 30 days to induce DE. Cognitive performance was assessed using the Morris water maze test followed by morin and metformin administration at the doses of 50 and 100 mg/kg, respectively, for 60 days. After 60 days of treatment, animals were subjected to the behavioral test and sacrificed to collect blood and brain and checked biochemical parameters. The treatment with morin could significantly reduce the escape latency time in Morris water maze test, blood glucose level, HbA1c, toxicity markers, lipid peroxidation products and protein carbonyl content, downregulated the expression of Bax, Caspase - 3 and Cytochrome C and upregulated Bcl-2, Bcl-XL, Akt, BDNF and TrkB expressions. Besides, enhanced the activities of antioxidant enzymes, and plasma insulin level. Histomorphological observations also confirmed the protective effect of morin on neuronal degeneration. Morin 50 mg once daily for 60 days was the most effective dose with a significant reduction in diabetes mediated complications in the brain associated with neuronal apoptosis and dysregulation of TrkB/Akt signaling.","PeriodicalId":49117,"journal":{"name":"Toxicology Mechanisms and Methods","volume":"32 1","pages":"695 - 704"},"PeriodicalIF":3.2,"publicationDate":"2022-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42196369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-11DOI: 10.1080/15376516.2022.2064258
Jagjeet Singh, Annu Phogat, Vijay Kumar, Vinay Malik
Abstract Background: Monocrotophos (MCP) is an organophosphate pesticide with well-known toxicity in mammals. Exposure of MCP is associated with altered molecular physiology at sub-cellular levels. This study investigated the efficacy of N-acetylcysteine (NAC) against MCP exposure mediated mitochondrial dysfunctions in hepatic tissue of rats. Methods: Male Wistar rats were given NAC (200 mg/kg b.wt), MCP (0.9 mg/kg b.wt) and NAC together with MCP, intragastrically for 28 consecutive days. Mitochondrial complexes activities were evaluated using biochemical analysis. mRNA expression of mitochondrial complexes subunits, PGC-1α and its downstream regulators were analyzed using polymerase chain reaction. Results: Exposure of MCP (0.9 mg/kg b.wt, intragastrically, 28 d) decreased mitochondrial complexes activities and gene expression of complexes subunits. The expression of PGC-1α, NRF-1, NRF-2, and Tfam was also reduced significantly. The administration of NAC (200 mg/kg b.wt, intragastrically, 28 d) significantly increased mitochondrial complexes activities and gene expression of complexes subunits. Additionally, NAC also maintained mitochondrial functions, and enhanced the gene expression of PGC-1α and its downstream regulators. Conclusion: The results of this study indicate that NAC prevents hepatic mitochondrial dysfunctions and maintains PGC-1α signaling. In conclusion, NAC might be speculated as a therapeutic agent for mitochondrial dysfunctions following toxic exposures.
{"title":"N-acetylcysteine ameliorates monocrotophos exposure-induced mitochondrial dysfunctions in rat liver","authors":"Jagjeet Singh, Annu Phogat, Vijay Kumar, Vinay Malik","doi":"10.1080/15376516.2022.2064258","DOIUrl":"https://doi.org/10.1080/15376516.2022.2064258","url":null,"abstract":"Abstract Background: Monocrotophos (MCP) is an organophosphate pesticide with well-known toxicity in mammals. Exposure of MCP is associated with altered molecular physiology at sub-cellular levels. This study investigated the efficacy of N-acetylcysteine (NAC) against MCP exposure mediated mitochondrial dysfunctions in hepatic tissue of rats. Methods: Male Wistar rats were given NAC (200 mg/kg b.wt), MCP (0.9 mg/kg b.wt) and NAC together with MCP, intragastrically for 28 consecutive days. Mitochondrial complexes activities were evaluated using biochemical analysis. mRNA expression of mitochondrial complexes subunits, PGC-1α and its downstream regulators were analyzed using polymerase chain reaction. Results: Exposure of MCP (0.9 mg/kg b.wt, intragastrically, 28 d) decreased mitochondrial complexes activities and gene expression of complexes subunits. The expression of PGC-1α, NRF-1, NRF-2, and Tfam was also reduced significantly. The administration of NAC (200 mg/kg b.wt, intragastrically, 28 d) significantly increased mitochondrial complexes activities and gene expression of complexes subunits. Additionally, NAC also maintained mitochondrial functions, and enhanced the gene expression of PGC-1α and its downstream regulators. Conclusion: The results of this study indicate that NAC prevents hepatic mitochondrial dysfunctions and maintains PGC-1α signaling. In conclusion, NAC might be speculated as a therapeutic agent for mitochondrial dysfunctions following toxic exposures.","PeriodicalId":49117,"journal":{"name":"Toxicology Mechanisms and Methods","volume":"32 1","pages":"686 - 694"},"PeriodicalIF":3.2,"publicationDate":"2022-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47632351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-11DOI: 10.1080/15376516.2022.2065226
Thalia Emmanoella Sebulsqui Saraiva, Gabriela Zimmermann Prado Rodrigues, Juliana Machado Kayser, E. Dallegrave, Nathália Pulz Maus, Andriele Veiverberg, Gabriel da Costa Berna, Andriéli Carolina Schuster, Maria Gabriela de Freitas, Marina Galdino da Rocha Pitta, I. da Rocha Pitta, G. Gehlen, A. H. Betti
Abstract Schizophrenia is a psychiatric disorder that affects 1% of the world population and is treated with antipsychotics, which may induce important biochemical and hematological alterations. Since it is necessary to verify the safety of new molecules with antipsychotic potential, the present study aimed to evaluate the oral toxicity of PT-31, a putative α2-adrenoreceptor agonist, after acute (2000 mg/kg) and repeated doses (28 days) gavage treatment, in three different doses: minimum effective dose in animal models (10 mg/kg), twice the dose (20 mg/kg), and four times the dose (40 mg/kg), as recommended by the OECD guidelines. Balb/C female adult mice were used, and biochemical, hematological, and histopathological analyses were performed. PT-31 10 and 20 mg/kg did not cause biochemical alterations related to hepatic and renal toxicity, and neither altered glycemic and lipid profiles. The preclinical dose of PT-31 also did not promote mice histopathological changes in the liver, kidney, and brain. In the hematimetric parameters, PT-31 only increased HGB at 20 mg/kg, and MCH and MCHC at 40 mg/kg. However, all the tested doses of PT-31 showed platelet increase, which must be better investigated. Therefore, further studies are needed to investigate the safety of PT-31 as a potential antipsychotic drug.
{"title":"Study of the acute and repeated dose 28-day oral toxicity in mice treated with PT-31, a molecule with a potential antipsychotic profile","authors":"Thalia Emmanoella Sebulsqui Saraiva, Gabriela Zimmermann Prado Rodrigues, Juliana Machado Kayser, E. Dallegrave, Nathália Pulz Maus, Andriele Veiverberg, Gabriel da Costa Berna, Andriéli Carolina Schuster, Maria Gabriela de Freitas, Marina Galdino da Rocha Pitta, I. da Rocha Pitta, G. Gehlen, A. H. Betti","doi":"10.1080/15376516.2022.2065226","DOIUrl":"https://doi.org/10.1080/15376516.2022.2065226","url":null,"abstract":"Abstract Schizophrenia is a psychiatric disorder that affects 1% of the world population and is treated with antipsychotics, which may induce important biochemical and hematological alterations. Since it is necessary to verify the safety of new molecules with antipsychotic potential, the present study aimed to evaluate the oral toxicity of PT-31, a putative α2-adrenoreceptor agonist, after acute (2000 mg/kg) and repeated doses (28 days) gavage treatment, in three different doses: minimum effective dose in animal models (10 mg/kg), twice the dose (20 mg/kg), and four times the dose (40 mg/kg), as recommended by the OECD guidelines. Balb/C female adult mice were used, and biochemical, hematological, and histopathological analyses were performed. PT-31 10 and 20 mg/kg did not cause biochemical alterations related to hepatic and renal toxicity, and neither altered glycemic and lipid profiles. The preclinical dose of PT-31 also did not promote mice histopathological changes in the liver, kidney, and brain. In the hematimetric parameters, PT-31 only increased HGB at 20 mg/kg, and MCH and MCHC at 40 mg/kg. However, all the tested doses of PT-31 showed platelet increase, which must be better investigated. Therefore, further studies are needed to investigate the safety of PT-31 as a potential antipsychotic drug.","PeriodicalId":49117,"journal":{"name":"Toxicology Mechanisms and Methods","volume":"32 1","pages":"705 - 715"},"PeriodicalIF":3.2,"publicationDate":"2022-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44190544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-11DOI: 10.1080/15376516.2022.2064257
A. Choudhary, Sanjiv Singh, V. Ravichandiran
Abstract Nanoparticles (range under 100 nm) prepared by different technology modes including physical, chemical, biological have many applications. Like in the same way silver nanoparticles are used for different beneficial actions like antimicrobial- antibacterial, antifungal and antiviral, anti-inflammatory, anticancer, water treatment, cosmetics, and in the textiles industry. As silver nanoparticles have shown wide application by different mechanisms against various pathophyisiological conditions. To maintain safety under their use, the study of the toxicity of silver nanoparticles has become more important. Health agencies like WHO, NIOSH, EPA, EFSA & EU have issued guidelines for unrisky exposure limit of silver nanopartricles in drinking water, food and breathing. The main purpose of this article is to summarize genotoxicity, cytotoxicity, neurotoxicity, reproductive toxicity of silver nanoparticles in both in vitro and in vivo studies focused on mechanism and methods of detection. The main mechanism of silver nanoparticles toxicity involves disruption of the mitochondrial respiratory chain, which results in the generation of ROS and the stoppage of ATP synthesis which further leads to a cascade of toxic events. ROS production measured by the technique like flow cytometry using DCFHDA dye and other method includes a confocal microscope, lipid peroxidation, etc. Different assay techniques used for evaluation of different kind of toxicities such as the comet assay, MTT assay, and histological assay, are also discussed.
{"title":"Toxicity, preparation methods and applications of silver nanoparticles: an update","authors":"A. Choudhary, Sanjiv Singh, V. Ravichandiran","doi":"10.1080/15376516.2022.2064257","DOIUrl":"https://doi.org/10.1080/15376516.2022.2064257","url":null,"abstract":"Abstract Nanoparticles (range under 100 nm) prepared by different technology modes including physical, chemical, biological have many applications. Like in the same way silver nanoparticles are used for different beneficial actions like antimicrobial- antibacterial, antifungal and antiviral, anti-inflammatory, anticancer, water treatment, cosmetics, and in the textiles industry. As silver nanoparticles have shown wide application by different mechanisms against various pathophyisiological conditions. To maintain safety under their use, the study of the toxicity of silver nanoparticles has become more important. Health agencies like WHO, NIOSH, EPA, EFSA & EU have issued guidelines for unrisky exposure limit of silver nanopartricles in drinking water, food and breathing. The main purpose of this article is to summarize genotoxicity, cytotoxicity, neurotoxicity, reproductive toxicity of silver nanoparticles in both in vitro and in vivo studies focused on mechanism and methods of detection. The main mechanism of silver nanoparticles toxicity involves disruption of the mitochondrial respiratory chain, which results in the generation of ROS and the stoppage of ATP synthesis which further leads to a cascade of toxic events. ROS production measured by the technique like flow cytometry using DCFHDA dye and other method includes a confocal microscope, lipid peroxidation, etc. Different assay techniques used for evaluation of different kind of toxicities such as the comet assay, MTT assay, and histological assay, are also discussed.","PeriodicalId":49117,"journal":{"name":"Toxicology Mechanisms and Methods","volume":"32 1","pages":"650 - 661"},"PeriodicalIF":3.2,"publicationDate":"2022-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47891747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-07DOI: 10.1080/15376516.2022.2063095
C. Miao, Dandan Fan
Abstract Objective In this study, differentially expressed genes (DEGs) and signaling pathways involved in diquat (DQ) and paraquat (PQ) poisoning were identified via bioinformatics analysis, in order to inform the development of novel clinical treatments. Methods Raw data from GSE153959 were downloaded from the Gene Expression Omnibus database. DEGs of the DQ vs. control (CON) and PQ vs. CON comparison groups were identified using R, and DEGs shared by the two groups were identified using TBtools. Subsequently, the shared DEGs were searched in the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, using the Database for Annotation, Visualization, and Integrated Discovery. A protein–protein interaction (PPI) network was constructed, and hub genes were identified using the cytoHubba plug-in in Cytoscape software. Finally, circos and contrast plots showing the DEGs shared between mouse and human chromosomes were constructed using TBtools. Results Thirty-one DEGs shared by the DQ and PQ groups were identified. Enriched biological process terms included positive regulation of cell proliferation and translation. Enriched cellular component terms included extracellular region, intracellular membrane-bounded organelle and mitochondrion. Enriched molecular function terms included transcription factor activity and sequence-specific double-stranded DNA binding. Enriched KEGG pathways included the interleukin-17 signaling pathway, tumor necrosis factor signaling pathway, and human T-cell leukemia virus 1 infection. The top 10 hub genes in the PPI network were prostaglandin-endoperoxide synthase 2 (Ptgs2), chemokine (C-X-C motif) ligand 2 (Cxcl2), colony-stimulating factor 2 (granulocyte-macrophage) (Csf2), matrix metallopeptidase 13 (Mmp13), amphiregulin (Areg), plasminogen activator, urokinase receptor (Plaur), fos-like antigen 1 (Fosl1), epiregulin (Ereg), activating transcription factor 3 (Atf3), and transferrin receptor (Tfrc). Cxcl2, Csf2, and Atf3 played important roles in the mitogen-activated protein kinase (MAPK) signaling pathway. Conclusions These pathways and DEGs may serve as targets for gene therapy.
【摘要】目的通过生物信息学分析，鉴定双甘菊(diquat, DQ)和百草枯(paraquat, PQ)中毒相关的差异表达基因(DEGs)和信号通路，为开发新的临床治疗方法提供依据。方法从Gene Expression Omnibus数据库下载GSE153959的原始数据。DQ组与对照组(CON)和PQ组与CON组的deg使用R进行鉴定，两组共有的deg使用TBtools进行鉴定。随后，使用Database for Annotation, Visualization, and Integrated Discovery在Gene Ontology和Kyoto Encyclopedia of Genes and Genomes (KEGG)数据库中检索共享的deg。构建蛋白-蛋白相互作用(PPI)网络，利用Cytoscape软件中的cytoHubba插件对枢纽基因进行鉴定。最后，使用TBtools构建显示小鼠和人类染色体之间共享的deg的环状图和对比图。结果DQ组和PQ组共鉴定出31个deg。丰富的生物过程术语包括细胞增殖和翻译的正调控。丰富的细胞成分包括胞外区、胞内膜结合细胞器和线粒体。富集的分子功能项包括转录因子活性和序列特异性双链DNA结合。富集的KEGG通路包括白细胞介素-17信号通路、肿瘤坏死因子信号通路和人t细胞白血病病毒1感染。PPI网络中排名前10位的枢纽基因分别是前列腺素内过氧化物合成酶2 (Ptgs2)、趋化因子(C-X-C基序)配体2 (Cxcl2)、集落刺激因子2(粒细胞-巨噬细胞)(Csf2)、基质金属肽酶13 (Mmp13)、双调节蛋白(Areg)、纤溶酶原激活剂、尿激酶受体(Plaur)、fos样抗原1 (Fosl1)、表调节蛋白(Ereg)、激活转录因子3 (Atf3)和转铁蛋白受体(Tfrc)。Cxcl2、Csf2和Atf3在丝裂原活化蛋白激酶(MAPK)信号通路中发挥重要作用。结论这些通路和deg可作为基因治疗的靶点。
{"title":"Identification of differentially expressed genes and pathways in diquat and paraquat poisoning using bioinformatics analysis","authors":"C. Miao, Dandan Fan","doi":"10.1080/15376516.2022.2063095","DOIUrl":"https://doi.org/10.1080/15376516.2022.2063095","url":null,"abstract":"Abstract Objective In this study, differentially expressed genes (DEGs) and signaling pathways involved in diquat (DQ) and paraquat (PQ) poisoning were identified via bioinformatics analysis, in order to inform the development of novel clinical treatments. Methods Raw data from GSE153959 were downloaded from the Gene Expression Omnibus database. DEGs of the DQ vs. control (CON) and PQ vs. CON comparison groups were identified using R, and DEGs shared by the two groups were identified using TBtools. Subsequently, the shared DEGs were searched in the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, using the Database for Annotation, Visualization, and Integrated Discovery. A protein–protein interaction (PPI) network was constructed, and hub genes were identified using the cytoHubba plug-in in Cytoscape software. Finally, circos and contrast plots showing the DEGs shared between mouse and human chromosomes were constructed using TBtools. Results Thirty-one DEGs shared by the DQ and PQ groups were identified. Enriched biological process terms included positive regulation of cell proliferation and translation. Enriched cellular component terms included extracellular region, intracellular membrane-bounded organelle and mitochondrion. Enriched molecular function terms included transcription factor activity and sequence-specific double-stranded DNA binding. Enriched KEGG pathways included the interleukin-17 signaling pathway, tumor necrosis factor signaling pathway, and human T-cell leukemia virus 1 infection. The top 10 hub genes in the PPI network were prostaglandin-endoperoxide synthase 2 (Ptgs2), chemokine (C-X-C motif) ligand 2 (Cxcl2), colony-stimulating factor 2 (granulocyte-macrophage) (Csf2), matrix metallopeptidase 13 (Mmp13), amphiregulin (Areg), plasminogen activator, urokinase receptor (Plaur), fos-like antigen 1 (Fosl1), epiregulin (Ereg), activating transcription factor 3 (Atf3), and transferrin receptor (Tfrc). Cxcl2, Csf2, and Atf3 played important roles in the mitogen-activated protein kinase (MAPK) signaling pathway. Conclusions These pathways and DEGs may serve as targets for gene therapy.","PeriodicalId":49117,"journal":{"name":"Toxicology Mechanisms and Methods","volume":"32 1","pages":"678 - 685"},"PeriodicalIF":3.2,"publicationDate":"2022-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48208284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-06DOI: 10.1080/15376516.2022.2063096
Jéssica Cristina Zoratto Romoli, Deborah Thais Palma Scanferla, Raul Gomes Aguera, Renata Sano Lini, G. C. Pante, C. B. Bueno Júnior, J. C. Castro, S. Mossini, C. Marchioni, M. M. Junior
Abstract Compilation studies related to toxicological aspects and also biological monitoring and analysis methods for specific fungicides and, mainly, those that belong to the class of the dithiocarbamates (DTCs) have not been carried out at least in the last ten years. DTCs – dimethyldithiocarbamates, ethylenebisditiocarbamates, propylenebisditiocarbamates – are organosulfur compounds that form complexes due to the presence of different chemical elements, which bind strongly and inhibit enzymes that are essential to the functioning of the organism, causing a serious proven adverse effect on biological systems, such as alteration of thyroid hormones, teratogenesis and neurotoxicity. It is still evident, as shown by world data, that the growing consumption of fungicides has increasingly exposed the population in general and, in particular, workers who deal with these substances. There is a scarcity of studies in the literature discussing the toxicological and analytical aspects that are important for understanding the real effects of DTCs and monitoring human exposure to them. Therefore, the aim of this work was to expose, in a comprehensive way and through a narrative review, gaps in research related to the fungicides of the DTCs class, their metabolites, as well as the toxicological and analytical aspects involved. The review is divided into two parts: (1) Toxicological aspects, including toxicokinetics, toxicodynamics and toxidromes; and (2) Analytical Toxicology, which comprises biomarkers, sample preparation and identification/quantification methods. Graphical Abstract
{"title":"Analytical and toxicological aspects of dithiocarbamates: an overview of the last 10 years","authors":"Jéssica Cristina Zoratto Romoli, Deborah Thais Palma Scanferla, Raul Gomes Aguera, Renata Sano Lini, G. C. Pante, C. B. Bueno Júnior, J. C. Castro, S. Mossini, C. Marchioni, M. M. Junior","doi":"10.1080/15376516.2022.2063096","DOIUrl":"https://doi.org/10.1080/15376516.2022.2063096","url":null,"abstract":"Abstract Compilation studies related to toxicological aspects and also biological monitoring and analysis methods for specific fungicides and, mainly, those that belong to the class of the dithiocarbamates (DTCs) have not been carried out at least in the last ten years. DTCs – dimethyldithiocarbamates, ethylenebisditiocarbamates, propylenebisditiocarbamates – are organosulfur compounds that form complexes due to the presence of different chemical elements, which bind strongly and inhibit enzymes that are essential to the functioning of the organism, causing a serious proven adverse effect on biological systems, such as alteration of thyroid hormones, teratogenesis and neurotoxicity. It is still evident, as shown by world data, that the growing consumption of fungicides has increasingly exposed the population in general and, in particular, workers who deal with these substances. There is a scarcity of studies in the literature discussing the toxicological and analytical aspects that are important for understanding the real effects of DTCs and monitoring human exposure to them. Therefore, the aim of this work was to expose, in a comprehensive way and through a narrative review, gaps in research related to the fungicides of the DTCs class, their metabolites, as well as the toxicological and analytical aspects involved. The review is divided into two parts: (1) Toxicological aspects, including toxicokinetics, toxicodynamics and toxidromes; and (2) Analytical Toxicology, which comprises biomarkers, sample preparation and identification/quantification methods. Graphical Abstract","PeriodicalId":49117,"journal":{"name":"Toxicology Mechanisms and Methods","volume":"32 1","pages":"637 - 649"},"PeriodicalIF":3.2,"publicationDate":"2022-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44524905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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