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Braz. j. biol ; 82: e247035, 2022. tab, graf
Article in English | LILACS | ID: biblio-1249265


Abstract The cockle Cerastoderma edule was exposed to four concentrations (5, 10, 20 and 70 μg L-1) of carbamazepine (CBZ). This anticonvulsant was found to alter the mussel behavior of by reducing its clearance rate (CR). Analysis of CBZ accumulation in tissues of C. edule was carried out using HPLC-UV after 48 or 96 hours of exposure. In addition, an overproduction of H2O2 by the bivalves was detected following exposure to CBZ but nitrite levels remained unchanged. Moreover, superoxide dismutase and catalase activities showed a significant increase in relation to their contact with CBZ. The activity of the biotransformation enzyme gluthatione-S-transferase did not change during exposure. Malondialdehyde (MDA) levels indicating cellular damage, increased when bivalves were exposed to 20 and 70 μg l-1 of carbamazepine for 96 h CBZ. The results also indicate that acetylcholinesterase activity (AChE) was inhibited in all CBZ concentrations during the 48 h exposure period. However, during the 96 h exposure period, AChE was only inhibited at the highest concentration. Further studies are needed now for more exploration of the toxicity of CBZ since it could be bioaccumulable throughout the food web and may affect non-target organisms.

Resumo O berbigão Cerastoderma edule foi exposto a quatro concentrações (5, 10, 20 e 70 μg L-1) de carbamazepina (CBZ). Este anticonvulsivante alterou o comportamento do mexilhão, reduzindo sua taxa de depuração (CR). A análise do acúmulo de CBZ nos tecidos de C. edule foi realizada por HPLC-UV após 48 ou 96 horas de exposição. Além disso, uma superprodução de H2O2 pelos bivalves foi detectada após a exposição à CBZ, mas os níveis de nitrito permaneceram inalterados. Além disso, as atividades de superóxido dismutase e catalase apresentaram aumento significativo em relação ao contato com CBZ. A atividade da enzima de biotransformação glutationa-S-transferase não se alterou durante a exposição. Os níveis de malondialdeído (MDA), indicando dano celular, aumentaram quando os bivalves foram expostos a 20 e 70 μg l-1 de carbamazepina por 96 h CBZ. Os resultados também indicam que a atividade da acetilcolinesterase (AChE) foi inibida em todas as concentrações de CBZ durante o período de exposição de 48 horas. No entanto, durante o período de exposição de 96 horas, a AChE foi inibida apenas na concentração mais alta. Mais estudos são necessários agora para uma maior exploração da toxicidade da CBZ, uma vez que pode ser bioacumulável em toda a cadeia alimentar e pode afetar organismos não alvo.

Animals , Water Pollutants, Chemical/toxicity , Bivalvia , Cardiidae , Carbamazepine/toxicity , Hydrogen Peroxide
Article in Chinese | WPRIM | ID: wpr-923775


Objective To test the activity of aromatic pyrrole-based compounds against cercariae of Schistosoma japonicum and test their acute toxicity to fish. Methods A series of aromatic pyrrole-based compounds were synthesized using 4-benzyl-5-(trifluoromethyl)-1H-pyrrole-3-nitrile as the lead compound. The synthesized compounds were prepared into solutions at concentrations of 10.00, 1.00, 0.10, 0.01 mg/L, and the activity of these solutions against S. japonicum cercariae was tested in 30 min, while 0.10 mg/L and 0.01 mg/L niclosamide solutions served as a positive control and dechlorinated water with 1% dimethyl sulfoxide (DMSO) was used as a negative control, with 10 to 30 cercariae of S. japonicum in each group. In addition, the compounds were prepared into solutions at concentrations of 0.50, 0.25, 0.12, 0.06, 0.03 mg/L, and their toxicity to zebrafish was tested in 72 h, while 0.15 mg/L and 0.30 mg/L niclosamide solutions served as a positive control and dechlorinated water with 1% DMSO was used as a negative control, with 10 zebrafishes in each group. Results A total of 7 aromatic pyrrole-based compounds were successfully synthesized. Treatment with compounds 102, 104 and 106 at a concentration of 0.01 mg/L for 30 min killed all S. japonicum cercariae, and compounds 105 and 107 showed no activity against cercariae. No death of cercariae was found in the blank control group, while treatment with 0.10 mg/L niclosamide for 10 min caused a 100% mortality rate of S. japonicum cercariae and 0.01 mg/L niclosamide failed to kill S. japonicum cercariae. No zebrafish death was found 72 h post-treatment with compounds 101, 104 and 105 at a concentration of 0.03 mg/L, and exposure to compounds 102, 103 and 106 at a concentration of 0.03 mg/L for 12 h resulted in a 100% mortality rate of zebrafish. No zebrafish death occurred 72 h post-treatment with 0.50 mg/L Compound 104, and no zebrafish death was found in the blank control group, while treatment with 0.30 mg/L niclosamide for 24 h resulted in a 100% mortality rate of zebrafish. Conclusions Compound 104 achieves a 100% mortality rate against S. japonicum cercariae at a concentration of 0.01 mg/L for 30 min, and causes no death of zebrafish at a concentration of 0.50 mg/L for 72 h, which may serve as a cercaricide candidate.

Rev. med. Risaralda ; 27(2): 126-144, jul.-dic. 2021. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1365899


Abstract Introduction: A high percentage of patients who survived poisoning will be transferred to the Intensive Care Unit (ICU) to continue their management in relation to the severity of the poisoning, and possible complications that arise in this scenario. The clinical results will depend on several factors, such as the ingested dose, the characteristics of the substance, the time of medical attention, and the pre-existing state of health of the patient. Objective: To review the clinical behavior of poisonings in the critically ill patient. Recent findings: The data bases that yielded relevant bibliographical results were Web of Sciences, Scopus, PubMed, SciELO, and bibliographic references published between 2012 and 2020 were chosen. Conclusions: The clinical behavior of poisonings in the critically ill patient is atypical. The intensivist must have an in-depth knowledge of the behavior and pathophysiology of the toxins since making a medical diagnosis on the stage of the critically ill patient is challenging. The integration of all possible medical tools is required to achieve this in the absence of clinical history, and the implementation of early management strategies is necessary to reach physiological restoration by using a continuous evaluation approach. The severity of poisoning in the critically ill patient demands interdisciplinary management that includes assessment by Clinical Toxicology.

Biomédica (Bogotá) ; 41(1): 99-110, ene.-mar. 2021. graf
Article in Spanish | LILACS | ID: biblio-1249062


Resumen | Introducción. El arsénico es un tóxico ambiental ampliamente diseminado en todo el mundo. En hombres y animales, diversos órganos y tejidos son blancos de sus efectos deletéreos, entre ellos, el los del sistema inmunológico. Objetivo. Determinar la intoxicación aguda por arsénico en tejidos y células diana de ratones Balb/c in vivo. Materiales y métodos. Se aplicó una inyección intraperitoneal de 9,5 o 19 mg/kg de arsenito de sodio (NaAsO2) o un volumen equivalente de solución fisiológica como control, en ratones Balb/c con 3 por cada grupo experimental. Tras media hora, los animales fueron sacrificados y se extrajeron bazos, timos, hígados, riñones y sangre. En cada muestra, se determinó la concentración de arsénico, polifenoles y hierro, y también, se evaluaron marcadores oxidativos, como peróxidos, productos avanzados de oxidación proteica y grupos sulfhidrilos libres. En los esplenocitos obtenidos del bazo, se determinaron la viabilidad celular y el potencial mitocondrial. Resultados. La dosis aguda inyectada de NaAsO2 redujo la función mitocondrial de los esplenocitos, lo que derivó en muerte celular. La presencia confirmada de arsénico en las muestras de bazo y la citotoxicidad resultante, produjeron disminución de los polifenoles y de los grupos sulfhidrilos libres, y alteraron el contenido y la distribución del hierro, pero no se aumentó la producción de peróxidos. Conclusión. Estos hallazgos aportan evidencia científica sobre los cambios en biomarcadores involucrados en la inmunotoxicidad del arsénico y ofrecen, además, una metodología para ensayar potenciales tratamientos frente a la acción deletérea de este compuesto en el sistema inmunológico.

Abstract | Introduction: Arsenic is an environmental toxic present worldwide. In men and animals, various organs and tissues are targets of its deleterious effects including those of the immune system. Objective: To determine acute arsenic toxicity in tissues and target cells of Balb/c mice using an in vivo methodology. Materials and methods: We injected Balb/c mice intraperitoneally with 9.5 or 19 mg/ kg of sodium arsenite (NaAsO2), or an equivalent volume of physiological solution as a control (with 3 per experimental group). After 30 minutes, the animals were sacrificed to obtain spleen, thymus, liver, kidneys, and blood. We determined arsenic, polyphenols, and iron concentrations in each sample and we evaluated the oxidative markers (peroxides, advanced products of protein oxidation, and free sulfhydryl groups). In splenocytes from the spleen, cell viability and mitochondrial potential were also determined. Results: The exposure to an acute dose of NaAsO2 reduced the mitochondrial function of splenocytes, which resulted in cell death. Simultaneously, the confirmed presence of arsenic in spleen samples and the resulting cytotoxicity occurred with a decrease in polyphenols, free sulfhydryl groups, and an alteration in the content and distribution of iron, but did not increase the production of peroxides. Conclusion: These findings provide scientific evidence about changes occurring in biomarkers involved in the immunotoxicity of arsenic and offer a methodology for testing possible treatments against the deleterious action of this compound on the immune system.

Arsenic , Mice , Oxidative Stress , Toxicity Tests, Acute , Immune System
Autops. Case Rep ; 11: e2021342, 2021. tab, graf
Article in English | LILACS | ID: biblio-1350167


Paraquat is a potent herbicide widely used in the Indian agriculture industry. Human fatality due to paraquat poisoning is not uncommon in this country. The primary effect of paraquat is on the lungs, and the resultant pulmonary damage leads to the patient's demise. There is a high mortality rate in paraquat poisoning as the treatment is usually supportive with no known antidote. There are limited human studies that have observed the histopathological changes in lungs in paraquat poisoning. The authors have discussed the time-related histopathological changes in lungs in paraquat poisoning on autopsy subjects. The role of anticoagulants and fibrinolytic agents in the treatment of this poisoning has also been discussed.

Humans , Male , Female , Paraquat/poisoning , Lung Injury/pathology , Lung/pathology , Autopsy , Toxicity Tests, Acute
Article in Chinese | WPRIM | ID: wpr-905961


Objective:To explore the acute toxicities and hepatotoxicities of aqueous extracts of Taxilli Herba from <italic>Morus alba</italic>, <italic>Toxicodendron</italic> <italic>trichocarpum</italic>, <italic>Camellia oleifera</italic>, <italic>Salix babylonica</italic>, <italic>Melia azedarach</italic>, and <italic>Nerium indicum</italic> against zebrafish model and the effect of different hosts on the toxicity of Taxilli Herba, hoping to provide a theoretical basis for the safe use of Taxilli Herba. Method:The normally developed AB zebrafish at 3-day post fertilization was selected for acute toxicity study. According to the results of preliminary toxicity experiments, the zebrafishes were treated with aqueous extracts of Taxilli Herba from different hosts at six doses, and their mortality was calculated 72 h later. GraphPad Prism 6.0 was used for plotting the dose-toxicity curve, followed by the calculation of their median lethal concentration (LC<sub>50</sub>) and 10% lethal concentration (LC<sub>10</sub>). The gz15Tg/+(AB) liver fluorescent protein transgenic zebrafish with normal development at 4-day post fertilization was applied for the hepatotoxicity study. The zebrafishes were divided into the low-, medium-, and high-dose groups of aqueous extracts of Taxilli Herba from six hosts, the positive control (acetaminophen) group, and the blank (embryo amniotic fluid) group, and then treated with the corresponding drugs. Seventy-two hours later, the liver morphology and fluorescent area changes in zebrafish were observed. And the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected. Result:The results of acute toxicity test demonstrated that the LC<sub>50</sub> values of water extracts of Taxilli Herba from <italic>M. alba</italic>, <italic>T.</italic> <italic>trichocarpum</italic>, <italic>C. oleifera</italic>, <italic>S. babylonica</italic>, <italic>M. azedarach</italic>, and <italic>N. indicum</italic> were 1.24, 0.94, 0.51, 0.38, 0.11, 0.09 g·L<sup>-1</sup>, respectively, and the LC<sub>10</sub> values were 0.70, 0.60, 0.35, 0.28, 0.08, 0.07 g·L<sup>-1</sup>, respectively. As revealed by hepatotoxicity test, compared with the blank group, the positive control group exhibited liver morphological changes, decreased fluorescent area (<italic>P</italic><0.01), and elevated ALT and AST activities (<italic>P</italic>< 0.01), suggesting that acetaminophen was hepatotoxic to zebrafish. However, there was no change in the liver morphology or fluorescent area of zebrafish in the low-, medium-, and high-dose groups of water extracts of Taxilli Herba from <italic>M. alba</italic>, and the ALT and AST activities were decreased. By contrast, the liver morphology and fluorescent areas in the medium- and high-dose groups of water extracts of Taxilli Herba from <italic>T.</italic> <italic>trichocarpum</italic>, <italic>C. oleifera</italic>, <italic>S. babylonica</italic>, <italic>M. azedarach</italic>, and <italic>N. indicum</italic> changed to varying degrees (<italic>P</italic><0.05, <italic>P</italic><0.01). Besides, the activities of both ALT and AST were also enhanced. These indicated that Taxilli Herba from <italic>M. alba</italic> had no hepatotoxicity to zebrafish, while that from <italic>T.</italic> <italic>trichocarpum</italic>, <italic>C. oleifera</italic>, <italic>S. babylonica</italic>, <italic>M. azedarach</italic>, and <italic>N. indicum</italic> showed varying degrees of hepatotoxicity to zebrafish. Conclusion:The toxicity of Taxilli Herba is host-dependent. Taxilli Herba from <italic>M. alba</italic> has no hepatotoxicity, but that from the other five hosts shows varying degrees of hepatotoxicity. Standardizing the host source may be an important measure to realize the medication safety of Taxilli Herba.

Article | IMSEAR | ID: sea-212515


Background: Aim of the study was to compare the response of altered fractionation schedule with concurrent chemo-radiation in patients with primary and the nodal disease.Methods: Total of 40 patients (20 in each arm) with stage 1- 4 squamous cell carcinoma of the head and neck with a performance status of 0-2 (ECOG) were included in the study. Arm A was altered fractionation schedule where in patients received 6 fractions per week to a total dose of 6600 cGy in 33 fractions. In Arm B, patients received conventional radiotherapy with concurrent chemotherapy three weekly Inj. of cisplatin (100 mg/m2). Patients were evaluated for acute toxicity every week using the Acute Radiation Morbidity Scoring Criteria. The response was assessed after 6 weeks and 12 weeks post treatment using the RECIST criteria. Data was statistically analyzed.Results: Seventeen patients in Arm A and 18 patients in Arm B completed the treatment. At the end of three months, In Arm A, 7 patients had complete response and in Arm B, 9 patients had complete response of the primary (p>0.05).  When the complete nodal response was compared in both the arms, there was no difference (2 vs 4 in Arm A vs Arm B resp.). But there were more partial nodal responders in Arm B (p = 0.016). The acute toxicities were comparable in both the arms.Conclusions: Altered fraction radiotherapy can be used in early lesions with minimal nodal burden but with locally advanced disease or large nodal burden addition of chemotherapy should not be avoided.

Electron. j. biotechnol ; 45: 38-45, May 15, 2020. ilus, graf, tab
Article in English | LILACS | ID: biblio-1177420


BACKGROUND: Taraxacum species (commonly known as dandelion) used as herbal medicine have been reported to exhibit an antiproliferative effect on hepatoma cells and antitumor activity in non-small-cell lung cancer cells. Although several investigations have demonstrated the safety of Taraxacum officinale, the safety of tissue-cultured plants of T. formosanum has not been assessed so far. Therefore, the present study examines the safety of the water extract of the entire plant of tissue cultured T. formosanum based on acute and subacute toxicity tests in rats, as well as the Ames tests. RESULTS: No death or toxicity symptoms were observed in the acute and subacute tests. The results of the acute test revealed that the LD50 (50% of lethal dose) value of the T. formosanum water extract for rats exceeded 5 g/kg bw. No abnormal changes in the body weight, weekly food consumption, organ weight, or hematological, biochemical, and morphological parameters were observed in the subacute toxicity test. Thus, the no observed adverse effect level (NOAEL) of T. formosanum water extract was estimated to be higher than 2.0 g/kg. Finally, the results of the Ames test revealed that T. formosanum water extract was not genotoxic at any tested concentration to any of five Salmonella strains. CONCLUSIONS: The water extract of tissue-cultured T. formosanum was non-toxic to rats in acute and subacute tests and exhibited no genotoxicity to five Salmonella strains.

Animals , Rats , Plant Extracts/toxicity , Taraxacum/toxicity , Tissue Culture Techniques/methods , Safety , Flavonoids/analysis , Chromatography, High Pressure Liquid , Urinalysis , Rats, Sprague-Dawley , Phenol/analysis , Toxicity Tests, Acute , Herbal Medicine , Taraxacum/chemistry , Serum , Cell Proliferation/drug effects , Toxicity Tests, Subacute , Mutagenicity Tests
Article | IMSEAR | ID: sea-215942


Background and Objectives:Duranta erectais used in folklore medicine for the treatment of myriad of diseases in Africa. The study was carried out to evaluate the safety of hydroethanolic leaves extract of D. erectain experimental rats in order to ascertain its potential toxic effects. Materials and Methods:The acute toxicity study was performed by fixed dose method at 5000 mg/kg. In the subacute study performed on both male and female rats, group I (control) received 1 mL of freshly distilled water, groups II, III, IV were treated with 100, 250 and 500 mg/kg of freshly prepared extract respectively for 28 days. At the end of the study, haematological and biochemical parameters were determined. Internal organs (kidney, liver, lung, heart, spleen, stomach, testes and uterus) were weighed.Results:50% lethal dose (LD50) of the extract was determined to be >5 g/kg body weight. The subacute toxicity assessment resulted in overall body weight increase, a change in relative organ weight of the liver, lung, stomach, and changes in the haematological indices such as HCT%, LYM%, RDW-SD/fL, MCHC, MCV/fL, P-LCR% and biochemical parameters namely ALT, AST, LDH and creatinine of the tested group relative to the normal. The positive activity of the extract on liver enzymes and LDH is an indication of its good hepatoprotective potential.Conclusion:The results affirmed that the extract is safe but could cause kidney problems when used for a prolonged period

Vaccimonitor (La Habana, Print) ; 29(1)ene.-abr. 2020. tab, graf
Article in Spanish | LILACS, CUMED | ID: biblio-1094637


Para el control y prevención del cólera humano se han llevado a cabo diferentes estrategias, entre las cuales, la vacunación es una de las medidas más eficaces. La evaluación preclínica de candidatos vacunales requiere de la demostración de la seguridad de los mismos, para lo cual los estudios toxicológicos son determinantes, al ser obligatorios y altamente regulados. Este estudio tuvo como objetivo demostrar la relevancia de las ratas Sprague Dawley como biomodelo a través de su respuesta inmunológica al candidato vacunal contra el cólera, vax-COLER®, utilizando la técnica de determinación de anticuerpos vibriocidas. Además, evaluar los efectos toxicológicos locales y sistémicos por la administración de una dosis de vax-COLER® a través de la evaluación de síntomas, del consumo de agua y alimentos, el peso corporal y estudios anatomopatológicos. La vacuna vax-COLER® resultó inmunogénica y no evidenció síntomas ni muertes, no hubo cambios en el peso corporal y los consumos de agua y alimentos se comportaron de forma similar entre todos los grupos. Los estudios anatomopatológicos solo mostraron cambios a nivel histológico en los ganglios linfáticos mesentéricos y placas de Peyer de los animales vacunados, con presencia de hiperplasia de los folículos secundarios subcapsulares, hallazgo que difirió significativamente con el resto de los grupos. Se concluye que la vacuna vax-COLER® es inmunogénica en ratas Sprague Dawley, demostrando la relevancia del biomodelo para la evaluación de la seguridad preclínica y que la aplicación de una dosis no produjo efectos tóxicos agudos generales ni locales(AU)

Different strategies have been carried out for the control and prevention of human cholera. Vaccination is one of the most effective strategies. Preclinical evaluation of vaccines needs to prove their safety; whereby toxicological studies are decisive. They are mandatory and highly regulated. This study was aimed to demonstrate the relevance of Sprague Dawley rats as a biomodel, through the immunological response to vax-COLER® cholera vaccine, using the technique of determination of vibriocidal antibodies. In addition, local and systemic toxicological effects were evaluated after administration of a dose of vax-COLER®; through the evaluation of symptoms, water and food consumption, body weight and anatomopathological studies. The vax-COLER® vaccine was immunogenic and showed no symptoms or deaths. No changes in body weight were detected, and food and water consumption were similar among all groups. The anatomopathological studies showed histological changes in the mesenteric lymph nodes and Peyer's patches of the vaccinated animals, with hyperplasia of the subcapsular secondary follicles, finding that differed significantly from the rest of the groups. It is concluded that vax-COLER® vaccine is immunogenic in Sprague-Dawley rats, demonstrating the relevance of the biomodel for the evaluation of preclinical safety, as well as that the application of a single dose did not produce acute general or local toxic effects(AU)

Animals , Rats , Cholera/prevention & control , Reference Drugs , Immunogenicity, Vaccine
Article | IMSEAR | ID: sea-210736


Caryota urens native to Srilanka and India grows in tropical and subtropical regions. It is rich in nutrition andshow pharmacological properties owing to the presence of flavonoids, coumarins, carbohydrates, and amino acids.However, scientific reports which guarantee the safety of C. urens are not available. Therefore, the intention of thecurrent investigation was to assess the potential toxicity of the hydroalcoholic extract of C. urens leaves (CULHA)in Wistar rats. In acute toxicity study, CULHA was administered at a single oral dose of 2,000 mg/kg body weight.In subacute toxicity study, CULHA was administered once a day at three dose levels of 100, 200, and 400 mg/kg body weight for 28 days. At the end of the treatment, animals were sacrificed; vital organs were removed andexamined histopathologically. Blood and serum samples were collected and processed immediately for the analysis ofhematological and biochemical parameters. During acute toxicity study, treatment-associated death or manifestationof toxic clinical symptoms were not seen. Furthermore, results of both acute and subacute toxicity group exposed toCULHA did not exhibit significant change in hematology, biochemical parameters, and histopathology. The resultsdemonstrated that CULHA did not possess potential to induce toxicity

Eng. sanit. ambient ; 25(1): 31-39, jan.-fev. 2020. tab, graf
Article in Portuguese | LILACS-Express | LILACS | ID: biblio-1090124


RESUMO A bacia hidrográfica do córrego Água Boa (Dourados, MS) sofre grande influência antrópica, tais como urbana e industrial. Levando-se em consideração sua importância para a manutenção de fauna, flora, indústria e população local, o estudo teve como objetivo avaliar a toxicidade de suas águas nos períodos seco e chuvoso de 2013, da nascente até próximo à sua foz, por meio de testes de toxicidade aguda com D. similis e D. rerio, além de análises físicas, químicas e de concentrações de metais pesados. Os resultados mostraram as variabilidades espacial e temporal dos parâmetros analisados. Além disso, constatou-se efeito tóxico no ponto 02 para D. rerio em ambos os períodos. As análises comprovaram a crítica situação de degradação do ambiente aquático estudado e alertam para os cuidados que deverão ser tomados. Portanto, sugere-se maior fiscalização por parte dos órgãos ambientais, bem como conscientização da população quanto às emissões de efluentes e resíduos no corpo hídrico, a fim de evitar sua degradação.

ABSTRACT The watershed of Água Boa Stream (Dourados/MS) suffers great anthropic influence, such as urban and industrial. Taking into consideration its importance for maintenance of fauna, flora, industry and local population, this study aimed to: assess the toxicity of its waters during the dry and rainy seasons of 2013, near the source to its mouth, through acute toxicity essays with D. similis and D. rerio, as well as physical, chemical and heavy metal concentration analyses. The results showed spatial and temporal variability of the analyzed parameters. Furthermore, a toxic effect was found at point 02 for D. rerio in both periods. The analyses confirmed the critical situation of degradation of the aquatic environment studied, and warns that precautions should be taken. Therefore, it is suggested that greater supervision by environmental agencies, as well as public awareness of the issue of waste and residues in the water body, in order to avoid its degradation.

Article | IMSEAR | ID: sea-200489


Background: Chromium, an essential trace mineral plays an important role in the metabolism of carbohydrate, fat and proteins. Chromium picolinate (Cr.Pic) is used in alternative medicine to treat chromium deficiency. Though Cr.Pic is increasingly used to treat diabetes and obesity, studies on its safety profile is limited.Methods: Acute toxicity study was conducted by oral administration of Cr.Pic (2000 mg/kg body weight). The animals were maintained another 14 days with once a day observation. For sub-chronic studies, test groups were treated with Cr.Pic 10 mg/kg/day for 90 days. Tests for hepatic and renal function were conducted. Effect of Cr.Pic on behavioural changes and motor co-ordination was done on every week. Histopathological studies were conducted on day 90 at the end of the experiment.Results: Acute toxicity study of Cr.Pic showed no signs of toxicity and mortality. Absence of any behavioural alteration or mortality during the period of 14 days indicates that Cr.Pic has no latent effect. Similar results were obtained with sub-chronic studies suggesting safety of Cr.Pic. Cr.Pic treated groups showed no changes in learning and motor co-ordination compared to the untreated group. No gross histopathological changes were seen in any group indicating safety of Cr.Pic.Conclusions: The present study conferred safety profile of Cr.Pic from normal results obtained in hepatic function, renal function, behavioural and histopathological studies, suggesting its safety.

J Ayurveda Integr Med ; 2020 Jan; 11(1): 45-52
Article | IMSEAR | ID: sea-214109


Background: The plant Rotula aquatica Lour. was traditionally well known due to its large number ofpharmacological action and medicinal uses. The plant is a necessary component of many Ayurvedic drugpreparations since historical times. It is widely used as a crucial ancient drug for kidney and bladderstones.Objectives: The main objective of the study was to evaluate the acute toxicity and anti inflammatoryefficacy of methanolic extract of R. aquatica Lour. in in vivo models.Materials and methods: The qualitative phytochemical analysis and invitro antioxidant activity of theroots of methanolic extract of R. aquatica Lour. (MERA) was evaluated. The acute toxicity effect of MERAwas evaluated with two different doses (550, 2000 mg/kg body weight), were administrated orally toWistar rats. The rats were observed for sign and symptoms of toxicity and mortality for 14 days. Theparameters measured including relative organ weight, blood, biochemical and histopathological parameters of hepatic and renal toxicity. The anti-inflammatory effect of MERA was also evaluated incarrageenan and dextran-induced paw edema models.Results: The phytochemical evaluation of MERA shows the presence of secondary metabolites like alkaloids, flavonoids, phenolics and tannins, phytosterols, reducing sugars, proteins and terpenoids. Theresults of in-vitro antioxidant evaluation of MERA reveal its capability to scavenging free radical at alower concentration. The MERA did not show any visible signs of toxicity up to the dose of 2000 mg/kgbody weight. The results obtained from our carrageenan and dextran-induced paw edema model studyalso proved the anti-inflammatory effect of MERA in rat model.Conclusion: The result shows the potential of MERA as an anti-inflammatory drug to reduce the signs ofinflammation devoid of any toxic effect.© 2018 The Authors. Published by Elsevier B.V. on behalf of Institute of Transdisciplinary Health Sciencesand Technology and World Ayurveda Foundation. This is an open access article under the CC BY-NC-NDlicense (

Rev. bras. cancerol ; 66(1)20200129.
Article in Portuguese | LILACS | ID: biblio-1094947


Introdução: O câncer de próstata é considerado a neoplasia maligna mais comum que acomete homens em todas as Regiões do país, à exceção do câncer de pele não melanoma. Se diagnosticado e tratado precocemente, o câncer de próstata tem alta taxa de cura; contudo, terapêuticas como a radioterapia podem gerar complicações agudas que podem impactar as atividades cotidianas. Apesar das complicações no pós-tratamento, a radioterapia tem sido um método bastante praticado e que apresenta resultados positivos, ocasionando melhoria da sobrevida livre de doença. Objetivo: Avaliar os principais fatores preditores de complicações agudas que acometem pacientes em tratamento radioterápico para câncer de próstata. Método: Para identificação de fatores preditores de complicações agudas pós-radioterapia, avaliaram-se, consecutiva e prospectivamente, 208 pacientes diagnosticados com adenocarcinoma de próstata tratados com radioterapia conformacional 3D em um centro referência vinculado ao SUS entre os anos 2016 e 2017. Realizou-se ainda avaliação retrospectiva de prontuários para coleta de dados adicionais. A análise estatística foi realizada por meio dos testes qui-quadrado, exato de Fisher, Anova e regressão logística ordinal. Resultados: Após análise da amostra, evidenciou-se que, entre as complicações agudas, as de maior incidência foram radiodermite, cistite e enterite/retite, de forma que tais complicações tiveram como fatores associados volume irradiado, tratamento prévio e sintomas prévios ao tratamento. Conclusão: O estudo sugere que, apesar da existência de complicações ao final do tratamento, a grande maioria é de baixa complexidade e que pacientes submetidos a procedimentos cirúrgicos prévios podem evoluir com presença de complicações mais graves.

Introduction: Prostate cancer is considered the most common malignancy that affects men in all regions of the country, except for non-melanoma skin cancer. If diagnosed and treated early, prostate cancer has a high cure rate; however, therapies such as radiotherapy can generate acute complications that can impact daily activities. Despite post-treatment complications, radiotherapy has been a widely practiced method and has shown positive results, leading to improved disease-free survival. Objective: To evaluate the main predictive factors for acute complications that affect patients undergoing radiotherapy for prostate cancer. Method: To identify predictive factors for acute post-radiotherapy complications, 208 patients diagnosed with prostate adenocarcinoma treated with 3D conformational radiotherapy were consecutively and prospectively evaluated at a referral center linked to SUS between the years 2016 and 2017. It was carried out retrospective evaluation of medical records to collect additional data. Statistical analysis was performed using the chi-square test, Fisher's exact, Anova and ordinal logistic regression. Results: After analyzing the sample, it was evidenced that among the acute complications, those with the highest incidence were radiodermatitis, cystitis, enteritis/rectitis, so that these complications had associated predictive factors as irradiated volume, previous treatment and symptoms. Conclusion: The study suggests that despite the existence of complications at the end of the treatment, the vast majority are of low complexity and that the patients submitted to previous surgical procedures can evolve with the presence of more severe complications.

Introducción: El cáncer de próstata se considera la neoplasia maligna más común que afecta a los hombres en todas las regiones del país, con la excepción del cáncer de piel no melanoma. Si se diagnostica y trata temprano, el cáncer de próstata tiene una alta tasa de curación; sin embargo, las terapias como la radioterapia pueden generar complicaciones agudas que pueden afectar las actividades diarias. A pesar de las complicaciones posteriores al tratamiento, la radioterapia ha sido un método ampliamente practicado y ha mostrado resultados positivos, lo que lleva a una mejor supervivencia libre de enfermedad. Objetivo: Evaluar los principales predictores de complicaciones agudas que afectan a los pacientes sometidos a radioterapia para el cáncer de próstata. Método: Para identificar los factores predictivos de complicaciones agudas posteriores a la radioterapia, 208 pacientes diagnosticados con adenocarcinoma de próstata tratados con radioterapia conformacional 3D fueron evaluados consecutiva y prospectivamente en un centro de referencia vinculado al SUS entre los años 2016 y 2017. Se realizó evaluación retrospectiva de registros médicos para recopilar datos adicionales. El análisis estadístico se realizó utilizando la prueba de chi-cuadrado, exacta de Fisher, de Anova y la regresión logística ordinal. Resultados: Después de analizar la muestra, se evidenció que, entre las complicaciones agudas, las de mayor incidencia fueron radiodermatitis, cistitis, enteritis/retitis y síntomas obstructivos, por lo que estas complicaciones tenían factores predictivos asociados, como el volumen irradiado, el tratamiento previo y los síntomas. Conclusión: El estudio sugiere que a pesar de la existencia de complicaciones al final del tratamiento, la gran mayoría son de baja complejidad. Como factores predictivos encontrados, se puede mencionar el volumen irradiado, la existencia de tratamiento previo y los síntomas en la consulta inicial.

Humans , Male , Adult , Middle Aged , Aged , Aged, 80 and over , Prognosis , Prostatic Neoplasms/radiotherapy , Adenocarcinoma/radiotherapy , Radiotherapy, Conformal/adverse effects , Radiodermatitis/radiotherapy , Brazil , Adenocarcinoma/complications , Retrospective Studies , Toxicity Tests, Acute , Cystitis/radiotherapy , Enteritis/radiotherapy
China Pharmacy ; (12): 1475-1462, 2020.
Article in Chinese | WPRIM | ID: wpr-822368


OBJECTIVE: To compare the contents of 4 components and toxicity from Miao medicine Chimonanthus nitens samples after drying in the shade ,oven drying ,steam,charring. METHODS :The contents of scopolin,fraxin,scopoletin and isofraxin were simultaneously determined by HPLC. The separation was performed on Welch-C18 column with mobile phase consisted of acetonitrile-water (gradient elution )at the flow rate of 1 mL/min. The detection wavelength was set at 214 nm,and column temperature was 30 ℃,and the sample size was 10 μL. Modified Karber method was used to determine the LD 50 and its 95%CI of different processed C. nitens to mice and evaluate its acute toxicity. RESULTS : The linear range of scopolin , fraxin, scopoletin and isofraxin were 0.019-1.856,0.016-1.616,0.009-0.920,0.006-0.624 μg(R2 were all not lower than 0.999 5). RSDs of precision , stability and reprodu-cibility tests were all lower than 2.0%(n=6). The average recoveries were 104.49%,102.22%, 101.45%,99.26%(all RSDs were lower than 2%,n=6). The contents of scopolin were 1.119 0%,0.904 3%, 1.068 4%and 0.036 4%;those o f fraxin were 0.867 8%,0.453 9%,0.423 7%and 0.020 5%;those of scopoletin ; those of isofraxidin were 0.110 2%,0.202 1%,0.208 1% and 0.249 4%in samples after drying in the shade ,oven CX-2018-001) drying, steam, charring. The LD 50 of 4 processedproducts were 4 118.13,3 733.36,1 643.61,>10 000 mg/kg samples ;95%CI were (3 748.87,4 523.76), (3 422.16,4 072.86),(1 520.90,1 776.23),(>10 000) mg/kg. CONCLUSIONS :HPLC method is reproducible and precise. It can be used to determine the contents of 4 components in different processed products of C. niten s. The contents of 4 components in different processed products , and the contents of glycosides toxicity components are decreased significantly. All the 4 processed products were low or non-toxic.

Article in Chinese | WPRIM | ID: wpr-821631


Objective To assess the acute toxicity of Cu2+, Cd2+, Hg2+ and Pb2+ to Oncomelania hupensis. Methods Cu2+, Cd2+, Hg2+ and Pb2+ solutions were prepared at five concentrations, and 10 snails were exposed to each concentration for 24, 48, 72 h and 96 h. Then, the inhibition of snail activity and snail death was observed, and the half maximal effective concentration (EC50) and median lethal concentrations (LC50) were estimated. Results The 24, 48, 72 h and 96 h EC50 values of Cu2+, Cd2+, Hg2+ and Pb2+ were 0.74, 0.56, 0.46, 0.37 mg/L, 4.79, 3.52, 1.70, 1.26 mg/L, 1.90, 1.49, 0.83, 0.76 mg/L and 21.40, 9.98, 7.90, 5.42 mg/L for snails, respectively. The 96 h LC50 values of Cu2+, Cd2+, Hg2+ and Pb2+ were 0.43, 2.96, 1.12 mg/L and 12.22 mg/L for snails, the safe concentrations were 0.004 3, 0.029 6, 0.011 2, 0.122 2 mg/L, respectively. Conclusion Cu2+ shows a high acute toxicity to snails, and Cd2+ and Hg2+ exhibit a moderate acute toxicity to snails, while Pb2+ is lowly toxic to snails.

Chinese Pharmaceutical Journal ; (24): 96-104, 2020.
Article in Chinese | WPRIM | ID: wpr-857795


OBJECTIVE: To conduct a single dose toxicology study of humanized anti-HER2 antibody drug conjugate for injection (HS630) and small molecular maytansine (DM1) in Sprague-Dawley rats. METHODS: Rats were divided randomly into nine groups including HS630 blank control group (0 mg•kg-1), DM1 vehicle control group (0 mg•kg-1), positive control group (Kadcyla®, 60 mg•kg-1), HS630 low-, middle-, high-dose groups (6, 20, 60 mg•kg-1) and DM1 low-, middle-, high-dose groups (0.10, 0.20, 0.40 mg•kg-1). Each group had twenty rats with female and male in half. Each rat was administered intravenously once. Animals were observed clinical symptoms consisting of behavior, fur and feces daily as well as body weight and food consumption twice or three times per week. Dissection was executed at D2 and D21 to examine gross anatomy with histopathological changes and weight main tissues. RESULTS: Rats given 60 mg•kg-1 HS630 appeared some adverse effects that 1/20 animal was dead. It was found that maximal tolerance dose of HS630 was 20 mg•kg-1 equivalent to 0.34 mg•kg-1 DM1. High dose could lead body weight and food consumption reduced and organ weights changed including liver, kidney, spleen and lung increased and testicle and epididymis decreased. Histopathological changes were observed in liver, spleen, lung, thymus, pancreas, kidney, mesenteric glands, intestinum, seminal vesicle, prostate, testicle, epididymis, adrenal gland, thyroid gland, pituitary body, eye, tongue, sternum (marrow), bone, skin, injection site. Rats given Kadcyla® showed the similar side effects with HS630. Rats given 20 mg•kg-1 HS630, abnormality weren′t observed in clinical symptom, body weight and food consumption. It could lead kidney and lung weighted. Histopathological changes were found in liver, spleen, thymus, pancreas, lung, kidney, mesenteric glands, duodenum, adrenal gland, pituitary body, skin. Rats given DM1 exhibited worse adverse effects that 2/20 animals were dead at 0.40 mg•kg-1 level. The maximal tolerance dose of DM1 was 0.20 mg•kg-1. High dose could lead body weight and food consumption reduced and organ weights changed including liver, spleen and adrenal gland increased and thymus decreased. Histopathological changes were found in liver, spleen, thymus, kidney, mesenteric glands, duodenum, intestinum, seminal vesicle, adrenal gland, pituitary body, eye, tongue, sternum (marrow), bone, skin. CONCLUSION: Rats given single dose of humanized anti-HER2 antibody-drug conjugate for injection (HS630) and chemical maytansine (DM1) respectively, the RESULTS: show that HS630, a kind of ADC products, have similar toxicological profile with Kadcyla® and exhibit better tolerability and wider safety margin when given the comparable dosage with DM1 based on the RESULTS: of tolerance, clinical symptoms, organ weight and histopathological findings.

Eng. sanit. ambient ; 24(6): 1115-1125, nov.-dez. 2019. graf
Article in Portuguese | LILACS-Express | LILACS | ID: biblio-1056116


RESUMO O declínio de anfíbios no mundo está cada vez maior e a perda de riqueza, muitas vezes, está associada a áreas agrícolas. O uso de agrotóxicos, em especial daqueles à base de glifosato, é cada vez maior e novas formulações estão sendo desenvolvidas. O presente trabalho avaliou a toxicidade aguda de um composto comercial com o princípio ativo glifosato e os efeitos comportamentais e morfológicos em girinos de Physalaemus cuvieri e Rhinella icterica. O primeiro mostrou-se mais sensível em relação ao formulado comercial do que o segundo e não houve diferenças significativas em relação às mudanças comportamentais e o aumento das concentrações do formulado entre as espécies, porém houve alterações morfológicas de peso e comprimento dos girinos de ambas espécies.

ABSTRACT The decline of amphibians in the world is increasing and the loss of wealth is often associated with agricultural areas. The use of pesticides, especially those based on glyphosate is increasing and new formulations are being developed. This study evaluated the acute toxicity of a commercial compound with glyphosate and behavioral and morphological effects on Physalaemus cuvieri and Rhinella icterica tadpoles; the former was more sensitive to the commercially formulated compound than R. icterica and there were no significant differences in relation to behavioral changes and increase compound concentrations among species, but there were morphological changes of weight and length of tadpoles of both species.

Braz. j. biol ; 79(4): 646-650, Nov. 2019. tab
Article in English | LILACS | ID: biblio-1001475


Abstract Deionized ammonium (NH3) acute toxicity (LC50-96h) in Patagonian blenny juveniles (Eleginops maclovinus) was assessed. Concentrations of deionized ammonium in salt water were prepared by using 24.09 ± 2.1 g ammonium chloride (NH4Cl). Fish were exposed in triplicates to different ammonium concentrations: 0.05; 0.094; 0.175; 0.325 and 0.605 mg NH3 L-1. Additionally, a control group was included. Experimental fish were kept at a photoperiod of 16:8h. Average temperatures were 16.24 ± 1.40 °C. Oxygen concentration was 7.16 ± 0.40 mg L -1. Water pH was 7.89 ± 0.2. LC50-96 h, was estimated by using Probit statistical method (95% intervals) using EPA software (1993). Juveniles of E. maclovinus showed a LC50-96h of 0.413mg NH3 L-1 value, different from most marine species. This study presents the first record of ammonium toxicity in marine species of Chile.

Resumo A toxicidade aguda (LC50-96h) de amônia deionizada (NH3 ) em Babosas-da-Patagônia (Eleginops maclovinus) juvenis foi avaliada. As concentrações de sal de amônia deionizada em água foram preparados com 24,09 ± 2,1 g de cloreto de amônio (NH4Cl). Os peixes foram expostos em triplicata a diferentes concentrações de amônia: 0,05; 0,094; 0,175; 0,325 e 0,605 mg L-1 de NH3. Além disso, um grupo de controle foi incluído. Peixes experimentais foram mantidos em fotoperíodo de 16: 8h. As temperaturas médias foram 16,24 + 1,40 °C. A concentração de oxigênio foi 16.24 +1.40°C mg L-1 . O pH da água foi de 7,89 + 0,2. h LC50-96h, foi estimada usando o método estatístico de Probit (intervalos de 95%) usando o software EPA (1993). E. maclovinus juvenis apresentaram uma LC 50-96h de 0.413mg NH3 L-1 valor diferente da maioria das espécies marinhas. Este estudo apresenta o primeiro registro de toxicidade amónio em espécies marinhas do Chile.

Animals , Perciformes/growth & development , Perciformes/physiology , Ammonium Compounds/toxicity , Fish Diseases/chemically induced , Temperature , Water Pollutants, Chemical/toxicity , Chile