Pub Date : 2020-09-01DOI: 10.1177/2397847320956562
E. Ugwuja, Nweze Vincent, I. C. Ikaraoha, S. Ohayi
Background: Studies on nutritional factors, including zinc in ameliorating the deleterious effects of potentially toxic elements have been scarce and the findings have been inconsistent. Aim: The aim of the present study was to evaluate the ameliorative potential of zinc against lead-induced toxicity in rats. Materials and methods: Male albino rats (n = 24) assigned into four groups of six/group: normal control (NC), zinc control (ZnC; 20 mg/kg ZnCl2), lead control (PbC; 50 mg/kg PbCl2) and lead plus zinc (Pb + Zn; 50 mg/kg PbCl2 plus 20 mg/kg ZnCl2), respectively were investigated. All administrations were through oral route and lasted for 42 days after which blood samples were collected for haematological and biochemical analyses using standard techniques. Results: Results showed that packed cell volume (PCV), haemoglobin concentration (HBC), red blood cell count (RBC) were significant (p < 0.05) reduced while total white blood cell count (TWBC), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC) and platelets were significantly elevated in PbC group in comparison with NC and ZnC. Also liver and renal function parameters as well as the liver and kidney malondialdehyde (MDA) were elevated while antioxidant enzymes; catalase (CAT) and superoxide dismutase (SOD) were significantly (p < 0.05) reduced in PbC group in comparison with NC and ZnC. Concentrations of lead were in the order: blood > liver > kidney in the PbC group. In addition to restoration of the altered parameters, administration of zinc in Pb + Zn group significantly reduced the raised lead concentrations in the plasma and organs. Conclusion: Reduction in body Pb burden and restoration of Pb-induced derangements in haematological and biochemical parameters by Zn strongly support the ameliorative property of Zn against Pb-induced toxicity.
{"title":"Zinc ameliorates lead toxicity by reducing body Pb burden and restoring Pb-induced haematological and biochemical derangements","authors":"E. Ugwuja, Nweze Vincent, I. C. Ikaraoha, S. Ohayi","doi":"10.1177/2397847320956562","DOIUrl":"https://doi.org/10.1177/2397847320956562","url":null,"abstract":"Background: Studies on nutritional factors, including zinc in ameliorating the deleterious effects of potentially toxic elements have been scarce and the findings have been inconsistent. Aim: The aim of the present study was to evaluate the ameliorative potential of zinc against lead-induced toxicity in rats. Materials and methods: Male albino rats (n = 24) assigned into four groups of six/group: normal control (NC), zinc control (ZnC; 20 mg/kg ZnCl2), lead control (PbC; 50 mg/kg PbCl2) and lead plus zinc (Pb + Zn; 50 mg/kg PbCl2 plus 20 mg/kg ZnCl2), respectively were investigated. All administrations were through oral route and lasted for 42 days after which blood samples were collected for haematological and biochemical analyses using standard techniques. Results: Results showed that packed cell volume (PCV), haemoglobin concentration (HBC), red blood cell count (RBC) were significant (p < 0.05) reduced while total white blood cell count (TWBC), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC) and platelets were significantly elevated in PbC group in comparison with NC and ZnC. Also liver and renal function parameters as well as the liver and kidney malondialdehyde (MDA) were elevated while antioxidant enzymes; catalase (CAT) and superoxide dismutase (SOD) were significantly (p < 0.05) reduced in PbC group in comparison with NC and ZnC. Concentrations of lead were in the order: blood > liver > kidney in the PbC group. In addition to restoration of the altered parameters, administration of zinc in Pb + Zn group significantly reduced the raised lead concentrations in the plasma and organs. Conclusion: Reduction in body Pb burden and restoration of Pb-induced derangements in haematological and biochemical parameters by Zn strongly support the ameliorative property of Zn against Pb-induced toxicity.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"111 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91103831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-08-12DOI: 10.1177/2397847320948516
Carr J. Smith, T. Perfetti, Gene M. Ko, Suzanne B. Hartigan
Chemicals possessing persistence (P) and high mobility (M) can present a hazard to drinking water resources by traversing natural barriers like riverbanks and artificial barriers found in water treatment plants. If the chemical is also toxic (T), i.e. classifiable as a PMT, the agent might be of particular concern as a potential drinking water contaminant. During routine water sampling, detection and quantitation of polar substances with high mobility can be problematic. The German Environment Agency (UBA) is considering the use of the Log Koc value as a proxy for mobility (M). Log Koc is related to Log P by the equation Log Koc = 0.69 Log P + 0.22. In this study, we demonstrate that chemicals with log P values at or very close to 2.0, 3.0 or 4.0 (and their concomitant log Koc values) can vary significantly in their chemical structures, molecular weights, molar volumes, and calculated molar refractivity (CMR), which is related to the mean polarizability of a molecule. The large degree of potential diversity in chemical structure and molecular parameters related to chemical behavior at a particular log P or log Koc value suggests that log Koc might not contain enough information to function as a standalone surrogate for the mobility (M) of a chemical, i.e. as related to its ability to move from a drinking water resource through the water plant purification process.
{"title":"High structural and molecular parameter diversity among chemicals with similar log P and log Koc values","authors":"Carr J. Smith, T. Perfetti, Gene M. Ko, Suzanne B. Hartigan","doi":"10.1177/2397847320948516","DOIUrl":"https://doi.org/10.1177/2397847320948516","url":null,"abstract":"Chemicals possessing persistence (P) and high mobility (M) can present a hazard to drinking water resources by traversing natural barriers like riverbanks and artificial barriers found in water treatment plants. If the chemical is also toxic (T), i.e. classifiable as a PMT, the agent might be of particular concern as a potential drinking water contaminant. During routine water sampling, detection and quantitation of polar substances with high mobility can be problematic. The German Environment Agency (UBA) is considering the use of the Log Koc value as a proxy for mobility (M). Log Koc is related to Log P by the equation Log Koc = 0.69 Log P + 0.22. In this study, we demonstrate that chemicals with log P values at or very close to 2.0, 3.0 or 4.0 (and their concomitant log Koc values) can vary significantly in their chemical structures, molecular weights, molar volumes, and calculated molar refractivity (CMR), which is related to the mean polarizability of a molecule. The large degree of potential diversity in chemical structure and molecular parameters related to chemical behavior at a particular log P or log Koc value suggests that log Koc might not contain enough information to function as a standalone surrogate for the mobility (M) of a chemical, i.e. as related to its ability to move from a drinking water resource through the water plant purification process.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"53 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85676910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-07-16DOI: 10.1177/2397847320940561
Carr J. Smith, T. Perfetti
The immobility of plants exerted evolutionary selection pressures resulting in the production of thousands of chemical substances thought to function as pesticides against predation by insects and animals. More than 10,000 plant-derived compounds have been isolated with the existence of about 100,000 such compounds postulated. In 1990, Ames et al. reported that 99.99% by weight of the pesticides ingested in a normal human diet are derived from natural plant-based sources. This surprising result raised the question as to whether these natural plant pesticides were toxic to humans. These authors examined a relatively small subset of natural pesticides and determined that their tumorigenicity in rodent cancer bioassays was similar to synthetic pesticides. In this analysis, we used standard United States Environmental Protection Agency programs to estimate the toxicity (T.E.S.T. 4.2) and persistence (EPI Suite 4.1) of a series of high-volume synthetic and natural pesticides. On average, synthetic pesticides were more persistent in the environment than were natural pesticides. This result is consistent with cost, time, and logistical constraints under which farmers apply a limited number of applications of pesticides during a crop cycle. Synthetic and natural pesticides are predicted to possess toxicities including mutagenicity and developmental toxicity. Synthetic pesticides are less often mutagenic.
植物的不动性施加了进化选择的压力，从而产生了数千种化学物质，这些化学物质被认为是抵御昆虫和动物捕食的杀虫剂。目前已分离出1万多种植物源性化合物，其中约有10万种是假定存在的。1990年，Ames等人报告说，正常人类饮食中摄入的99.99%的农药(按重量计)来自天然植物性来源。这一令人惊讶的结果提出了一个问题，即这些天然植物杀虫剂是否对人类有毒。这些作者研究了一小部分天然农药，并确定它们在啮齿动物癌症生物测定中的致瘤性与合成农药相似。在本分析中，我们使用标准的美国环境保护署程序来估计一系列大容量合成和天然农药的毒性(T.E.S.T. 4.2)和持久性(EPI Suite 4.1)。平均而言，合成农药比天然农药在环境中的持久性更强。这一结果与农民在一个作物周期内施用有限数量农药的成本、时间和后勤限制相一致。据预测，合成农药和天然农药都具有致突变性和发育毒性。合成农药通常不太具有诱变性。
{"title":"A comparison of the persistence, toxicity, and exposure to high-volume natural plant-derived and synthetic pesticides","authors":"Carr J. Smith, T. Perfetti","doi":"10.1177/2397847320940561","DOIUrl":"https://doi.org/10.1177/2397847320940561","url":null,"abstract":"The immobility of plants exerted evolutionary selection pressures resulting in the production of thousands of chemical substances thought to function as pesticides against predation by insects and animals. More than 10,000 plant-derived compounds have been isolated with the existence of about 100,000 such compounds postulated. In 1990, Ames et al. reported that 99.99% by weight of the pesticides ingested in a normal human diet are derived from natural plant-based sources. This surprising result raised the question as to whether these natural plant pesticides were toxic to humans. These authors examined a relatively small subset of natural pesticides and determined that their tumorigenicity in rodent cancer bioassays was similar to synthetic pesticides. In this analysis, we used standard United States Environmental Protection Agency programs to estimate the toxicity (T.E.S.T. 4.2) and persistence (EPI Suite 4.1) of a series of high-volume synthetic and natural pesticides. On average, synthetic pesticides were more persistent in the environment than were natural pesticides. This result is consistent with cost, time, and logistical constraints under which farmers apply a limited number of applications of pesticides during a crop cycle. Synthetic and natural pesticides are predicted to possess toxicities including mutagenicity and developmental toxicity. Synthetic pesticides are less often mutagenic.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76033148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-07-10DOI: 10.1177/2397847320940557
Carr J. Smith, T. Perfetti
The maximum tolerated dose (MTD) provides the highest probability of a positive result in a toxicology bioassay. The assumption underlying the MTD in animal bioassays is that adverse effects at very high doses are qualitatively the same as those occurring at low doses. In contrast with the MTD, the optimal top dose in a toxicology animal study is the highest dose that does not produce a pathological end point that presents no risk at lower doses, for example, the dose below which cytotoxicity induces tumors in the absence of genotoxicity or other carcinogenic mechanisms. Normal concentrations or biological activity levels of many substances necessary for normal physiological function induce pathology when found at high levels. For example, the demonstration that ingestion of abnormally high levels of certain dietary fats can cause or exacerbate atherosclerosis in relevant animal models like rhesus macaques does not demonstrate that normal levels of these fats should be considered as toxic. Excessive estrogenic stimulation is associated with breast, ovarian, and endometrial cancers. This does not imply that normal age-appropriate levels of estrogen are toxic. Normal wound healing is associated with transforming growth factors beta 1 and 2. Excessive stimulation of fibroblasts by these growth factors results in hypertrophic scarring and keloid formation. An understanding of the mode of action of a test substance can facilitate the selection of dose levels much higher than those expected to be experienced by humans, but not beyond a dose level at which pathology is an experimental artefact of the high-dose level.
{"title":"High-dose exposure to synthetic chemicals, hormones, or homeostatic substances in experimental animals or humans can induce artefactual pathology","authors":"Carr J. Smith, T. Perfetti","doi":"10.1177/2397847320940557","DOIUrl":"https://doi.org/10.1177/2397847320940557","url":null,"abstract":"The maximum tolerated dose (MTD) provides the highest probability of a positive result in a toxicology bioassay. The assumption underlying the MTD in animal bioassays is that adverse effects at very high doses are qualitatively the same as those occurring at low doses. In contrast with the MTD, the optimal top dose in a toxicology animal study is the highest dose that does not produce a pathological end point that presents no risk at lower doses, for example, the dose below which cytotoxicity induces tumors in the absence of genotoxicity or other carcinogenic mechanisms. Normal concentrations or biological activity levels of many substances necessary for normal physiological function induce pathology when found at high levels. For example, the demonstration that ingestion of abnormally high levels of certain dietary fats can cause or exacerbate atherosclerosis in relevant animal models like rhesus macaques does not demonstrate that normal levels of these fats should be considered as toxic. Excessive estrogenic stimulation is associated with breast, ovarian, and endometrial cancers. This does not imply that normal age-appropriate levels of estrogen are toxic. Normal wound healing is associated with transforming growth factors beta 1 and 2. Excessive stimulation of fibroblasts by these growth factors results in hypertrophic scarring and keloid formation. An understanding of the mode of action of a test substance can facilitate the selection of dose levels much higher than those expected to be experienced by humans, but not beyond a dose level at which pathology is an experimental artefact of the high-dose level.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80850726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-07-08DOI: 10.1177/2397847320938666
M. Bastaki, V. Lu, Michel Aubanel, H. Bialk, Christopher Choi, J. Demyttenaere, Maodo Malick Diop, Sylvain Etter, Xing Han, Christie L Harman, G. Krammer, J. Schnabel, Cody L. Wilson, Sean V. Taylor
The essential oil of peppermint and one of its natural constituents, (R)-(+)-pulegone, are approved flavorings added to food worldwide. (R)-(+)-Pulegone and peppermint oil were tested separately in two independent bacterial reverse mutation assays according to Organisation for Economic Co-operation and Development Guideline 471. Both flavorings did not produce any evidence of mutagenicity up to cytotoxic concentrations in either the presence or the absence of exogenous metabolic activation.
{"title":"Absence of mutagenic activity in the bacterial reverse mutation assay with pulegone and peppermint oil","authors":"M. Bastaki, V. Lu, Michel Aubanel, H. Bialk, Christopher Choi, J. Demyttenaere, Maodo Malick Diop, Sylvain Etter, Xing Han, Christie L Harman, G. Krammer, J. Schnabel, Cody L. Wilson, Sean V. Taylor","doi":"10.1177/2397847320938666","DOIUrl":"https://doi.org/10.1177/2397847320938666","url":null,"abstract":"The essential oil of peppermint and one of its natural constituents, (R)-(+)-pulegone, are approved flavorings added to food worldwide. (R)-(+)-Pulegone and peppermint oil were tested separately in two independent bacterial reverse mutation assays according to Organisation for Economic Co-operation and Development Guideline 471. Both flavorings did not produce any evidence of mutagenicity up to cytotoxic concentrations in either the presence or the absence of exogenous metabolic activation.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72834880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-07-01DOI: 10.1177/2397847320931484
M. de Kort, K. Weber, B. Wimmer, Katharina Wilutzky, P. Neuenhahn, P. Allingham, A. Léoni
The physiological and health status of control animals may vary. Due to this variation, it is important to define acceptable ranges of control hematology parameters to gain a better understanding of adverse and non-adverse effects of test substances. After generating historical control data for two Wistar rat strains (RccHan™:WIST and Crl:WI(Han)) from different breeders, the data sets were statistically analyzed using Minitab®. After noticing that single outliers can affect the study control data set, the respective outliers were verified relative to the available histopathology findings, for example, inflammatory pulmonary lesions following vehicle aspiration or spontaneous sperm granuloma affecting the health status and hematology data of the respective animals. Such data points were excluded from the control data set. Comparing both data sets, it was obvious that different blood sampling and anesthesia methods as well as strain differences may result in slightly different values. After excluding the outliers, a data set from animals with presumably good health status was generated to define acceptable ranges and severity degrees. To evaluate effects, possibly influencing hematology parameters and defined acceptable ranges, selected vehicles and different study types were observed.
{"title":"Historical control data for hematology parameters obtained from toxicity studies performed on different Wistar rat strains: Acceptable value ranges, definition of severity degrees, and vehicle effects","authors":"M. de Kort, K. Weber, B. Wimmer, Katharina Wilutzky, P. Neuenhahn, P. Allingham, A. Léoni","doi":"10.1177/2397847320931484","DOIUrl":"https://doi.org/10.1177/2397847320931484","url":null,"abstract":"The physiological and health status of control animals may vary. Due to this variation, it is important to define acceptable ranges of control hematology parameters to gain a better understanding of adverse and non-adverse effects of test substances. After generating historical control data for two Wistar rat strains (RccHan™:WIST and Crl:WI(Han)) from different breeders, the data sets were statistically analyzed using Minitab®. After noticing that single outliers can affect the study control data set, the respective outliers were verified relative to the available histopathology findings, for example, inflammatory pulmonary lesions following vehicle aspiration or spontaneous sperm granuloma affecting the health status and hematology data of the respective animals. Such data points were excluded from the control data set. Comparing both data sets, it was obvious that different blood sampling and anesthesia methods as well as strain differences may result in slightly different values. After excluding the outliers, a data set from animals with presumably good health status was generated to define acceptable ranges and severity degrees. To evaluate effects, possibly influencing hematology parameters and defined acceptable ranges, selected vehicles and different study types were observed.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89597526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-06-30DOI: 10.1177/2397847320936281
O. Palacios, Heather Nelson Cortes, B. Jenks, K. Maki
Hormones and hormone-like substances, for example, phytoestrogens, are food components that can be endogenously produced by a food source or occur secondary to farming practices. The hormone content of foods has been studied for decades, and safety evaluations in the United States and Europe indicate that naturally occurring hormones found in foods are safe for human consumption. More recent studies have focused on the role of certain hormones found in specific foods (e.g. dairy or soy) and their potential health effects. However, limited summaries exist on food content of hormones and hormone-like phytoestrogens in the context of a comprehensive US diet and implications, if any, of their daily consumption for overall health. This review provides an outline of hormone biosynthesis and functions in the body; discusses the more commonly studied, naturally occurring hormones in food and their biological role within food; estimates relative dietary contribution and when available, bioavailability, of naturally occurring food hormones; and summarizes the potential health associations of their intake in food. Based on the review of the scientific literature, the hormone content of typical serving sizes of commonly consumed foods is undetectable or in quantities that fall well within safety guidelines without any evidence for adverse effects on health.
{"title":"Naturally occurring hormones in foods and potential health effects","authors":"O. Palacios, Heather Nelson Cortes, B. Jenks, K. Maki","doi":"10.1177/2397847320936281","DOIUrl":"https://doi.org/10.1177/2397847320936281","url":null,"abstract":"Hormones and hormone-like substances, for example, phytoestrogens, are food components that can be endogenously produced by a food source or occur secondary to farming practices. The hormone content of foods has been studied for decades, and safety evaluations in the United States and Europe indicate that naturally occurring hormones found in foods are safe for human consumption. More recent studies have focused on the role of certain hormones found in specific foods (e.g. dairy or soy) and their potential health effects. However, limited summaries exist on food content of hormones and hormone-like phytoestrogens in the context of a comprehensive US diet and implications, if any, of their daily consumption for overall health. This review provides an outline of hormone biosynthesis and functions in the body; discusses the more commonly studied, naturally occurring hormones in food and their biological role within food; estimates relative dietary contribution and when available, bioavailability, of naturally occurring food hormones; and summarizes the potential health associations of their intake in food. Based on the review of the scientific literature, the hormone content of typical serving sizes of commonly consumed foods is undetectable or in quantities that fall well within safety guidelines without any evidence for adverse effects on health.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84763567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-06-09DOI: 10.1177/2397847320931500
G. Ihegboro, A. J. Alhassan, C. Ononamadu, Mohamed Sani Sule
The pharmacological effects of medicinal plants are due to the presence of certain chemical compounds present in them. Previous studies have shown that crude extracts of Tapinanthus bangwensis (T. bangwensis) possess hepatocurative potential. However, the present study aims on evaluating the antioxidant activity as well as identifying the chemical compounds in ethylacetate fraction of T. bangwensis that ameliorate carbon tetrachloride-induced hepatotoxicity in Wistar rats. Six subfractions of ethylacetate fraction were obtained by column chromatography. The antioxidant activity was determined by 2,2-diphenyl-1-picrylhydrazine (DPPH), biochemical assay determined by spectrophotometry, and compound elucidation by liquid chromatography–mass spectroscopy (LC-MS) analysis. The DPPH result shows that subfraction F0 exhibited the strongest antioxidant activity followed by F4 while F1 exhibited the lowest. Oral administration of 100 mg/kg body weight of the subfractions of ethylacetate fraction of T. bangwensis increases superoxide dismutase and catalase activities and also glutathione level and decreases malondialdehyde level compared to the positive control group. Subsequently, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, and conjugated bilirubin were reduced while albumin and total protein levels increased compared to the positive control group. However, there were no significant differences between the positive control group and the group induced and treated with the subfractions at p < 0.05. The histopathology study shows normal hepatocyte distribution with no fat deposit in the induced and treated groups while fatty liver was observed in the positive group. The anti-hepatotoxic effect was higher in F4 than in other subfraction treated groups. Hence, the LC-MS analysis of F4 reveals the presence of 8-hydroxyluteolin-8-glucoside, Avicularin, Fisetin-7-glucoside, Isoscutellarein-7-xyloside, and Isovitexin, respectively, and has been reported to exhibit antioxidant and hepatocurative activities. It can be concluded that the hepatocurative effect could be due to the chemical compounds identified above.
药用植物的药理作用是由于其中存在某些化合物。已有研究表明，扁文Tapinanthus bangwensis (T. bangwensis)粗提物具有治疗肝脏疾病的潜力。然而，本研究旨在评价班氏霉乙酸乙酯部位的抗氧化活性，并鉴定其改善四氯化碳诱导的Wistar大鼠肝毒性的化合物。通过柱层析得到乙酸乙酯的6个亚组分。用2,2-二苯基-1-苦味肼(DPPH)测定其抗氧化活性，用分光光度法测定生化活性，用液相色谱-质谱(LC-MS)分析化合物。DPPH结果表明，亚组分F0抗氧化活性最强，F4次之，F1最低。与阳性对照组相比，口服班氏霉乙酸乙酯亚组分100 mg/kg体重可提高小鼠超氧化物歧化酶和过氧化氢酶活性，提高谷胱甘肽水平，降低丙二醛水平。随后，与阳性对照组相比，天冬氨酸转氨酶、丙氨酸转氨酶、碱性磷酸酶、总胆红素和偶联胆红素水平降低，白蛋白和总蛋白水平升高。阳性对照组与亚组分诱导组及处理组比较差异无统计学意义(p < 0.05)。组织病理学观察显示，诱导组和治疗组肝细胞分布正常，无脂肪沉积，阳性组肝细胞呈脂肪肝。F4组抗肝毒作用明显高于其他亚组。因此，LC-MS分析显示F4分别含有8-羟基木犀草素-8-葡萄糖苷、Avicularin、非甾酮-7-葡萄糖苷、异木犀草苷-7-木糖苷和异牡荆苷，并有报道称其具有抗氧化和肝治疗活性。由此可见，其肝治疗作用可能与上述化合物有关。
{"title":"Identification of bioactive compounds in ethylacetate fraction of Tapinanthus bangwensis leaves that ameliorate CCl4-induced hepatotoxicity in Wistar rats","authors":"G. Ihegboro, A. J. Alhassan, C. Ononamadu, Mohamed Sani Sule","doi":"10.1177/2397847320931500","DOIUrl":"https://doi.org/10.1177/2397847320931500","url":null,"abstract":"The pharmacological effects of medicinal plants are due to the presence of certain chemical compounds present in them. Previous studies have shown that crude extracts of Tapinanthus bangwensis (T. bangwensis) possess hepatocurative potential. However, the present study aims on evaluating the antioxidant activity as well as identifying the chemical compounds in ethylacetate fraction of T. bangwensis that ameliorate carbon tetrachloride-induced hepatotoxicity in Wistar rats. Six subfractions of ethylacetate fraction were obtained by column chromatography. The antioxidant activity was determined by 2,2-diphenyl-1-picrylhydrazine (DPPH), biochemical assay determined by spectrophotometry, and compound elucidation by liquid chromatography–mass spectroscopy (LC-MS) analysis. The DPPH result shows that subfraction F0 exhibited the strongest antioxidant activity followed by F4 while F1 exhibited the lowest. Oral administration of 100 mg/kg body weight of the subfractions of ethylacetate fraction of T. bangwensis increases superoxide dismutase and catalase activities and also glutathione level and decreases malondialdehyde level compared to the positive control group. Subsequently, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, and conjugated bilirubin were reduced while albumin and total protein levels increased compared to the positive control group. However, there were no significant differences between the positive control group and the group induced and treated with the subfractions at p < 0.05. The histopathology study shows normal hepatocyte distribution with no fat deposit in the induced and treated groups while fatty liver was observed in the positive group. The anti-hepatotoxic effect was higher in F4 than in other subfraction treated groups. Hence, the LC-MS analysis of F4 reveals the presence of 8-hydroxyluteolin-8-glucoside, Avicularin, Fisetin-7-glucoside, Isoscutellarein-7-xyloside, and Isovitexin, respectively, and has been reported to exhibit antioxidant and hepatocurative activities. It can be concluded that the hepatocurative effect could be due to the chemical compounds identified above.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79479512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-06-05DOI: 10.1177/2397847320929991
A. Athané, J. Demol, Sandra Brosset-Vincent, Corinne Aguenou, S. Krisa, A. Courtois, H. Griffiths, Olivier Cagnac
The microalgae Galdieria sulphuraria, which belong to the class of cyanidiophyceae, are thermostable at temperatures up to 55°C and have successfully been cultivated under controlled fermentation conditions to produce a protein-rich biomass from which a natural blue proteinaceous pigment, C-phycocyanin can be isolated. The C-phycocyanin has potential use as a colour additive and as a dietary supplement. This C-phycocyanin is resistant to acidic pH down to 2.75, in contrast to the one from Spirulina, which is already used as a colouring agent in agri-food applications. To further promote its use for industrial applications, we report, here, the results of a safety evaluation on a G. sulphuraria extract enriched to 33% C-phycocyanin. This was conducted in a 90-day repeated dose toxicity study in rats at doses from 250 to 4000 mg/kg body weight/day, in bacterial reversal mutation test at doses from 312.5 to 5000 µg/plate and in micronucleus assay at doses from 500 to 2000 µg/mL. Overall, our results indicated that the C-phycocyanin extract from G. sulphuraria did not exert any noteworthy adverse effect of toxicological significance in any of the system used for its safety evaluation, even if some minor changes were observed. According to the 90-day repeated dose toxicity study, no observed adverse effect level of 4000 mg/kg/day could be estimated. In conclusion, this study supports the safety of soluble fraction enriched with C-phycocyanin from G. sulphuraria for its use as food ingredient or supplement.
微藻Galdieria suluraria属于藻蓝藻科，在55°C的温度下具有耐热性，并已成功地在受控发酵条件下培养出富含蛋白质的生物质，从中可以分离出天然的蓝色蛋白色素C-藻蓝藻蛋白。c -藻蓝蛋白有作为颜色添加剂和膳食补充剂的潜在用途。这种c -藻蓝蛋白可以抵抗pH值低至2.75的酸性，这与螺旋藻形成了鲜明对比，后者已经被用作农业食品中的着色剂。为了进一步促进其工业应用，我们报告了一种富含33% c -藻蓝蛋白的硫酸根提取物的安全性评价结果。在大鼠中进行了为期90天的重复剂量毒性研究，剂量为250至4000 mg/kg体重/天，在细菌逆转突变试验中，剂量为312.5至5000µg/平板，在微核试验中，剂量为500至2000µg/mL。总的来说，我们的结果表明，即使观察到一些微小的变化，在用于其安全性评估的任何系统中，硫酸根c -藻蓝蛋白提取物也没有产生任何值得注意的毒理学意义的不良影响。根据90天重复给药毒性研究，未观察到4000mg /kg/天的不良反应水平。综上所述，本研究支持富c -藻蓝蛋白可溶性组分作为食品配料或补充剂的安全性。
{"title":"The safety evaluation of phycocyanin-enriched Galdieria sulphuraria extract using 90-day toxicity study in rats and in vitro genotoxicity studies","authors":"A. Athané, J. Demol, Sandra Brosset-Vincent, Corinne Aguenou, S. Krisa, A. Courtois, H. Griffiths, Olivier Cagnac","doi":"10.1177/2397847320929991","DOIUrl":"https://doi.org/10.1177/2397847320929991","url":null,"abstract":"The microalgae Galdieria sulphuraria, which belong to the class of cyanidiophyceae, are thermostable at temperatures up to 55°C and have successfully been cultivated under controlled fermentation conditions to produce a protein-rich biomass from which a natural blue proteinaceous pigment, C-phycocyanin can be isolated. The C-phycocyanin has potential use as a colour additive and as a dietary supplement. This C-phycocyanin is resistant to acidic pH down to 2.75, in contrast to the one from Spirulina, which is already used as a colouring agent in agri-food applications. To further promote its use for industrial applications, we report, here, the results of a safety evaluation on a G. sulphuraria extract enriched to 33% C-phycocyanin. This was conducted in a 90-day repeated dose toxicity study in rats at doses from 250 to 4000 mg/kg body weight/day, in bacterial reversal mutation test at doses from 312.5 to 5000 µg/plate and in micronucleus assay at doses from 500 to 2000 µg/mL. Overall, our results indicated that the C-phycocyanin extract from G. sulphuraria did not exert any noteworthy adverse effect of toxicological significance in any of the system used for its safety evaluation, even if some minor changes were observed. According to the 90-day repeated dose toxicity study, no observed adverse effect level of 4000 mg/kg/day could be estimated. In conclusion, this study supports the safety of soluble fraction enriched with C-phycocyanin from G. sulphuraria for its use as food ingredient or supplement.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"44 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85527366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-05-13DOI: 10.1177/2397847320922940
Carr J. Smith, T. Perfetti
Exposure to chemicals produced by natural processes is ubiquitous. First, in addition to the products of normal metabolism produced in humans of normal body weight, adipose tissue produces a large number of chemicals, including estrogen, testosterone from the produced estrogen, thyroid-stimulating hormone, leptin and approximately 500 other molecules termed adipokines, and a large number of inflammatory mediators. Second, the gut biome contains approximately the same number of bacteria as cells found in the entire body and produces a large number of small molecules. Third, the overwhelming majority (99.9%) of pesticide exposure occurs during ingestion of natural plant pesticides from eating vegetables. Fourth, consumption of cooked muscles meats leads to significant exposure to mutagenic and carcinogenic heterocyclic amines, polycyclic aromatic amines, and nitropyrenes. Fifth, many common beverages, for example, beer, coffee, and tea contain organic chemicals that display mutagenic activity. As compared with man-made production levels, from 1945 to 2015, an estimated 5000-fold more organic compounds were produced by a variety of natural processes, including common wood-degrading and forest litter-degrading fungi, microorganisms in temperate and boreal forest soils, bacteria in marine sponges, marine macro-algae, volcanoes, and forest fires. Exposure to these naturally produced organic compounds occurs via inhalation of ambient air, ingestion of food and water, and contact with soil, freshwater, and seawater. Contact with several thousand different endogenous or exogenous chemicals per day is unavoidable. This understanding might assist in better allocating resources toward controlling exposures to agents of highest concern as determined by current concepts of chronic disease causation.
{"title":"Exposure to chemicals formed from natural processes is ubiquitous","authors":"Carr J. Smith, T. Perfetti","doi":"10.1177/2397847320922940","DOIUrl":"https://doi.org/10.1177/2397847320922940","url":null,"abstract":"Exposure to chemicals produced by natural processes is ubiquitous. First, in addition to the products of normal metabolism produced in humans of normal body weight, adipose tissue produces a large number of chemicals, including estrogen, testosterone from the produced estrogen, thyroid-stimulating hormone, leptin and approximately 500 other molecules termed adipokines, and a large number of inflammatory mediators. Second, the gut biome contains approximately the same number of bacteria as cells found in the entire body and produces a large number of small molecules. Third, the overwhelming majority (99.9%) of pesticide exposure occurs during ingestion of natural plant pesticides from eating vegetables. Fourth, consumption of cooked muscles meats leads to significant exposure to mutagenic and carcinogenic heterocyclic amines, polycyclic aromatic amines, and nitropyrenes. Fifth, many common beverages, for example, beer, coffee, and tea contain organic chemicals that display mutagenic activity. As compared with man-made production levels, from 1945 to 2015, an estimated 5000-fold more organic compounds were produced by a variety of natural processes, including common wood-degrading and forest litter-degrading fungi, microorganisms in temperate and boreal forest soils, bacteria in marine sponges, marine macro-algae, volcanoes, and forest fires. Exposure to these naturally produced organic compounds occurs via inhalation of ambient air, ingestion of food and water, and contact with soil, freshwater, and seawater. Contact with several thousand different endogenous or exogenous chemicals per day is unavoidable. This understanding might assist in better allocating resources toward controlling exposures to agents of highest concern as determined by current concepts of chronic disease causation.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90302738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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