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1.
Neurotoxicology ; 89: 184-190, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35167857

RESUMEN

Epoxiconazole is among the most widely applied pesticides worldwide. The increased use of these products could cause toxic effects on human health which are mainly associated with its residues in food or occupational exposure in agriculture. The brain is the principal target of lipophilic compounds exposure, while the data of brain injury induced by Epoxiconazole remains unclear. The purpose of our investigation was to assess the cytotoxic and genotoxic effects of the epoxiconazole in rat Pheochromocytoma (PC 12). We found that epoxiconazole could reduce the viability and proliferation of PC12 cells, induce the DNA damage, nuclear condensation, cytoskeleton network disruption and enhance the apoptotic cell death. Intracellular biochemical assay proved that EPX induces the loss of mitochondrial membrane potential (ΔΨm) and activates caspase-3. Indeed, EPX instigated ROS generation in neuronal cells, which is accompanied by an increase of lipid peroxidation as confirmed by the high levels of MDA. Interestingly, Pre-treatment of PC12 cells with the ROS scavenger N-acetylcysteine mitigated EPX-provoked DNA fragmentation and enhancement of apoptosis. Our results demonstrate that the genotoxic and cytotoxic outcomes of EPX are mediated through a ROS-dependent pathway in PC12 cells.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales , Feocromocitoma , Neoplasias de las Glándulas Suprarrenales/inducido químicamente , Animales , Apoptosis , Supervivencia Celular , Daño del ADN , Compuestos Epoxi , Estrés Oxidativo , Células PC12 , Feocromocitoma/inducido químicamente , Ratas , Especies Reactivas de Oxígeno/metabolismo , Triazoles
3.
Endocrine ; 71(2): 459-466, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32965630

RESUMEN

PURPOSE: Bisphenol-A (BPA) is an endocrine-disrupting chemical that may affect the hormones and their receptors. The aim of this study is to determine whether BPA has an effect on the development of nonfunctional adrenal incidentaloma (NFAI). METHODS: Fifty patients who were admitted to endocrinology outpatient clinics and diagnosed as NFAI were included in the study. Fifty healthy people without adrenal mass and adrenal pathology in the upper abdominal computerized tomography or magnetic resonance imaging were also included as control group. Age, gender and body mass index of the study groups were similar. The serum samples for BPA were stored at -80 °C in refrigerator until working in the lab. Serum BPA levels were measured using ELISA technique. RESULTS: Mean serum BPA level was 7.06 ± 3.96 ng/ml in NFAI patients and 4.79 ± 3.01 ng/ml in control group. Serum BPA level was significantly higher in NFAI group than control group (p = 0.001). Serum BPA levels were also found to be significantly higher in women with NFAI than in men with NFAI (p = 0.019). CONCLUSIONS: The mechanisms of NFAI development have not been clarified yet. Increased BPA exposure with developed industrialization may play a role in NFAI formation. For the reduction of BPA exposure, the use of plastic prepacked products, plastic containers, and safety measures are essential for public health.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales , Neoplasias de las Glándulas Suprarrenales/inducido químicamente , Neoplasias de las Glándulas Suprarrenales/diagnóstico por imagen , Compuestos de Bencidrilo/toxicidad , Índice de Masa Corporal , Femenino , Hormonas , Humanos , Hallazgos Incidentales , Masculino
4.
S D Med ; 73(2): 78-80, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32135056

RESUMEN

Catecholamine-induced cardiomyopathy (CIC) and pheochromocytoma are both rare entities, and their exact incidence and prevalence are unknown. Pheochromocytoma has been implicated as one of the causes of CIC or Takotsubo syndrome (TTS) by means of case reports and retrospective reviews. However, the evaluation of any patient with TTS and pheochromocytoma is often faced with multiple challenges due to its rarity and atypical presentations, which subsequently leads to delay in diagnosis. Here, we present a case of a 51-year old female who had three distinct episodes of TTS and now presented in a hypertensive emergency with angina, palpitations, headache, nausea, and vomiting. She was treated for non-ST elevation myocardial infarction (NSTEMI) but coronary angiogram revealed patent coronary arteries. Due to the paroxysmal nature of her hypertensive emergencies and variable blood pressure response, pheochromocytoma was suspected. On further evaluation, she was found to have elevated metanephrines and a 6.3 cm left adrenal mass on CT scan. This case emphasizes the importance of considering or identifying pheochromocytoma as an underlying primary etiology for recurrent episodes of TTS and related concerns such as choice of anti-hypertensive agents.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales , Catecolaminas , Feocromocitoma , Neoplasias de las Glándulas Suprarrenales/inducido químicamente , Neoplasias de las Glándulas Suprarrenales/diagnóstico , Catecolaminas/efectos adversos , Urgencias Médicas , Femenino , Humanos , Persona de Mediana Edad , Feocromocitoma/inducido químicamente , Feocromocitoma/diagnóstico , Estudios Retrospectivos
5.
Biochimie ; 171-172: 147-157, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32105813

RESUMEN

The importance of cytochrome P450 (CYP)-derived arachidonic acid (AA) metabolites, 20-hydroxyeicosatetraenoic acid (20-HETE) and epoxyeicosatrienoic acids (EETs) as tumor growth promotors has already been described in several cancer types. The aim of this study was to evaluate the role of these compounds in the biology of pheochromocytoma/paraganglioma. These tumors originate from chromaffin cells derived from adrenal medulla (pheochromocytomas) or extra-adrenal autonomic paraganglia (paragangliomas), and they represent the most common hereditary endocrine neoplasia. According to mutations in the driver genes, these tumors are divided in two clusters: pseudo-hypoxic and kinase-signaling EETs, but not 20-HETE, exhibited a potent ability to sustain growth in a murine pheochromocytoma cell line (MPC) in vitro, EETs promoted an increase in cell proliferation and a decrease in cell apoptosis. In a mouse model of pheochromocytoma, the inhibition of CYP-mediated AA metabolism using 1-aminobenzotriazol resulted in slower tumor growth, a decreased vascularization, and a lower final volume. Also, the expression of AA-metabolizing CYP monooxygenases was detected in tumor samples from human origin, being their apparent abundance and the production of both metabolites higher in tumors from the kinase-signaling cluster. This is the first evidence of the importance of CYP- derived AA metabolites in the biology and development of pheochromocytoma/paraganglioma tumors.


Asunto(s)
Ácido 8,11,14-Eicosatrienoico/análogos & derivados , Neoplasias de las Glándulas Suprarrenales/inducido químicamente , Sistema Enzimático del Citocromo P-450/metabolismo , Ácidos Hidroxieicosatetraenoicos/farmacología , Feocromocitoma/inducido químicamente , Ácido 8,11,14-Eicosatrienoico/farmacología , Adolescente , Neoplasias de las Glándulas Suprarrenales/patología , Adulto , Animales , Línea Celular Tumoral , Niño , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Neovascularización Patológica , Feocromocitoma/patología , Adulto Joven
6.
J Cell Biochem ; 121(2): 1778-1789, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31642100

RESUMEN

3-Acetyl-11-keto-ß-boswellic acid (AKBA), a pentacyclic triterpenic acid present in gum resin of Boswellia serrata, has been found to possess antioxidant and neuroprotective properties. In this study, we aimed to examine protective properties of AKBA against glutamate-induced neuronal injury. To investigate the effects of AKBA (2.5-10 µM) on glutamate injury in neuron-like cells PC12 and N2a, two treatment regimens (incubation for 2 or 0 hours before glutamate exposure) were used. Then, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method was used to determine viability of the cells. Cellular redox status was evaluated using fluorimetry and comet assays. Annexin V/propidium iodide double staining and Western blot analysis of relative apoptotic proteins were conducted. Based on the results, 24 hours incubation with glutamate (8 mM) increased the cell mortality of PC12 and N2a (P < .001). However, AKBA (2.5-10 µM) enhanced the cell viability in both treatment regimens (P < .001). Also co- and pretreatment with AKBA significantly attenuated lipid peroxidation, reactive oxygen species production, and DNA injury (P < .05 and P < .001). AKBA also restored the activity of cellular superoxide dismutase under glutamate toxicity; this effect was seen to be more significant during the pretreatment regimen (P < .001). Moreover, Western blot analysis indicated that AKBA inhibited glutamate-induced programmed cell death through depressing the elevation of the expression ratio of Bax/Bcl-2 and cleaved-caspase-3 proteins, concentration-dependently. Overall, the present findings suggest the neuroprotective activities of AKBA against glutamate-induced cell injury probably by inhibiting oxidative damage and reducing apoptotic cell death.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales/tratamiento farmacológico , Apoptosis/efectos de los fármacos , Ácido Glutámico/toxicidad , Neuroblastoma/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Feocromocitoma/tratamiento farmacológico , Triterpenos/farmacología , Neoplasias de las Glándulas Suprarrenales/inducido químicamente , Neoplasias de las Glándulas Suprarrenales/patología , Animales , Peroxidación de Lípido/efectos de los fármacos , Ratones , Neuroblastoma/inducido químicamente , Neuroblastoma/patología , Células PC12 , Feocromocitoma/inducido químicamente , Feocromocitoma/patología , Ratas
9.
Am J Emerg Med ; 36(6): 1124.e1-1124.e2, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29534916

RESUMEN

Metoclopramide (MCP) is a commonly used anti-emetic in the emergency department (ED). Its use is generally well tolerated; although infrequent adverse reactions such as extrapyramidal reactions or tardive dyskinesia are reported. However, many ED providers are not familiar with the potentially life-threatening hypertensive emergency that can be precipitated by MCP administration in patients with pheochromocytoma. A previously healthy 36-year-old woman presented to the ED with headache and nausea. She developed acute hypertensive emergency (acute agitation, worsening headache, chest pain and wide complex tachycardia) when her blood pressure (BP) increased to 223/102mmHg (initial BP, 134/86mmHg) after receiving intravenous MCP. Her hospital course was complicated by multi-organ injury, including acute respiratory distress syndrome requiring venous-venous extracorporeal membrane oxygenation, non-ST elevation myocardial infarction, cardiogenic shock, acute liver failure, and oliguric kidney injury requiring continuous renal replacement therapy. CT scan showed previously undiagnosed large right adrenal mass (5.9cm). The diagnosis of pheochromocytoma was confirmed after adrenalectomy. Drug-induced acute pheochromocytoma crisis is a rare event. Early recognition and appropriate blood pressure management with clevidipine, nicardipine, or phentolamine is essential.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales/inducido químicamente , Antieméticos/efectos adversos , Servicios Médicos de Urgencia , Hipertensión/inducido químicamente , Metoclopramida/efectos adversos , Feocromocitoma/inducido químicamente , Choque Cardiogénico/inducido químicamente , Neoplasias de las Glándulas Suprarrenales/fisiopatología , Neoplasias de las Glándulas Suprarrenales/cirugía , Adrenalectomía , Adulto , Antieméticos/administración & dosificación , Femenino , Cefalea , Humanos , Hipertensión/fisiopatología , Metoclopramida/administración & dosificación , Náusea/tratamiento farmacológico , Feocromocitoma/fisiopatología , Feocromocitoma/cirugía , Choque Cardiogénico/fisiopatología , Resultado del Tratamiento
10.
Rev Med Interne ; 37(2): 135-8, 2016 Feb.
Artículo en Francés | MEDLINE | ID: mdl-26404523

RESUMEN

INTRODUCTION: Pheochromocytoma is suggested by the presence of severe and paroxysmal hypertension associated with hyperadrenergy clinical signs. If the diagnosis of pheochromocytoma is ruled out, a pseudo-pheochromocytoma should be considered. We report a clinical observation of pseudo-pheochromocytoma due to iproniazid, a non-selective irreversible monoamine oxidase (MAO) A and B inhibitor in a patient with bipolar disorder. CASE REPORT: A 78-year-old Caucasian male patient treated by iproniazid was hospitalized for depressive relapse. After several episodes of syncopes related to orthostatic hypotension, the patient presented hypertensive crisis. Urinary normetanephrines were increased to twice the upper limit of the normal range. Iproniazid was discontinued. Patient hemodynamic was rapidly stabilized and sympathetic hypertonia diminished. The urinary measurements normalized within two months. The abdominal imaging eliminated an adrenal tumor. CONCLUSION: Iproniazid could be responsible for severe irregular blood pressure associated with abnormal catecholamine metabolism (i.e. pseudo-pheochromocytoma).


Asunto(s)
Neoplasias de las Glándulas Suprarrenales/inducido químicamente , Iproniazida/efectos adversos , Inhibidores de la Monoaminooxidasa/efectos adversos , Feocromocitoma/inducido químicamente , Anciano , Humanos , Masculino
11.
Toxicology ; 333: 195-205, 2015 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-25896363

RESUMEN

Occupational exposure to cobalt is of widespread concern due to its use in a variety of industrial processes and the occurrence of occupational disease. Due to the lack of toxicity and carcinogenicity data following exposure to cobalt, and questions regarding bioavailability following exposure to different forms of cobalt, the NTP conducted two chronic inhalation exposure studies in rats and mice, one on soluble cobalt sulfate heptahydrate, and a more recent study on insoluble cobalt metal. Herein, we compare and contrast the toxicity profiles following whole-body inhalation exposures to these two forms of cobalt. In general, both forms were genotoxic in the Salmonella T98 strain in the absence of effects on micronuclei. The major sites of toxicity and carcinogenicity in both chronic inhalation studies were the respiratory tract in rats and mice, and the adrenal gland in rats. In addition, there were distinct sites of toxicity and carcinogenicity noted following exposure to cobalt metal. In rats, carcinogenicity was observed in the blood, and pancreas, and toxicity was observed in the testes of rats and mice. Taken together, these findings suggest that both forms of cobalt, soluble and insoluble, appear to be multi-site rodent carcinogens following inhalation exposure.


Asunto(s)
Cobalto/toxicidad , Neoplasias de las Glándulas Suprarrenales/inducido químicamente , Neoplasias de las Glándulas Suprarrenales/patología , Médula Suprarrenal/efectos de los fármacos , Médula Suprarrenal/patología , Animales , Pruebas de Carcinogenicidad , Cobalto/química , Femenino , Neoplasias Hematológicas/inducido químicamente , Neoplasias Hematológicas/patología , Exposición por Inhalación , Neoplasias Pulmonares/inducido químicamente , Neoplasias Pulmonares/patología , Masculino , Ratones , Pruebas de Mutagenicidad , Neoplasias Pancreáticas/inducido químicamente , Neoplasias Pancreáticas/patología , Ratas Endogámicas F344 , Sistema Respiratorio/efectos de los fármacos , Sistema Respiratorio/patología , Medición de Riesgo , Salmonella/efectos de los fármacos , Salmonella/genética , Solubilidad , Especificidad de la Especie , Testículo/efectos de los fármacos , Testículo/patología , Factores de Tiempo , Pruebas de Toxicidad Crónica
12.
Eur J Med Res ; 19: 53, 2014 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-25288254

RESUMEN

BACKGROUND: Symptomatic paroxysmal hypertension without significantly elevated catecholamine concentrations and with no evidence of an underlying adrenal tumor is known as pseudopheochromocytoma. METHODS: We describe the case of a female patient with paroxysmal hypertensive crises accompanied by headache, vertigo, tachycardia, nausea and altered mental status. Previously, she was treated for a longer period with alprazolam due to panic disorder. Causes of secondary hypertension were excluded. Neurological triggers (intracranial tumor, cerebral vascular lesions, hemorrhage, and epilepsy) could not be detected. RESULTS: Setting of the diagnosis of pseudopheochromocytoma treatment was initiated with alpha- and beta-blockers resulting in reduced frequency of symptoms. Alprazolam was restarted at a daily dose of 1 mg. The patient's clinical condition improved rapidly and the dosage of alpha- and beta-blockers could be decreased. CONCLUSIONS: We conclude that the withdrawal of an anxiolytic therapeutic regimen may generate sympathetic overdrive resulting in life-threatening paroxysmal malignant hypertension and secondary encephalopathy. We emphasize that pseudopheochromocytoma can be diagnosed only after exclusion of the secondary causes of hypertension. We highlight the importance of a psychopharmacological approach to this clinical entity.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales/patología , Ansiolíticos/administración & dosificación , Hipertensión/patología , Feocromocitoma/patología , Síndrome de Abstinencia a Sustancias/patología , Neoplasias de las Glándulas Suprarrenales/inducido químicamente , Neoplasias de las Glándulas Suprarrenales/complicaciones , Alprazolam/administración & dosificación , Alprazolam/efectos adversos , Ansiolíticos/efectos adversos , Femenino , Cefalea/complicaciones , Cefalea/patología , Humanos , Hipertensión/inducido químicamente , Hipertensión/complicaciones , Persona de Mediana Edad , Náusea/complicaciones , Náusea/patología , Trastorno de Pánico , Feocromocitoma/inducido químicamente , Feocromocitoma/complicaciones , Taquicardia/complicaciones , Taquicardia/patología , Vértigo/complicaciones , Vértigo/patología
13.
Chem Biol Interact ; 224: 1-12, 2014 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-25289773

RESUMEN

The carcinogenicity potential of canagliflozin, an inhibitor of SGLT2, was evaluated in a 2-year rat study (10, 30, and 100 mg/kg). Rats showed an increase in pheochromocytomas, renal tubular tumors, and testicular Leydig cell tumors. Systemic exposure multiples at the highest dose relative to the maximum clinical dose were 12- to 21-fold. Pheochromocytomas and renal tubular tumors were noted in both sexes at 100 mg/kg. Leydig cell tumors were observed in males in all dose groups and were associated with increased luteinizing hormone levels. Hyperplasia was increased in the adrenal medulla at 100 mg/kg, but only a limited increase in simple tubular hyperplasia was observed in the kidney of males at 100 mg/kg. Hyperostosis occurred and was accompanied by substantial effects on calcium metabolism, including increased urinary calcium excretion and decreased levels of calcium regulating hormones (1,25-dihydroxyvitamin D and parathyroid hormone). A separate study with radiolabeled calcium confirmed that increased urinary calcium excretion was mediated via increased calcium absorption from the gastrointestinal tract. It was hypothesized that, at high doses, canagliflozin might have inhibited glucose absorption in the intestine via SGLT1 inhibition that resulted in glucose malabsorption, which increased calcium absorption by stimulating colonic glucose fermentation and reducing intestinal pH. Pheochromocytomas and adrenal medullary hyperplasia were attributed to altered calcium homeostasis, which have a known relationship in the rat. In conclusion, Leydig cell tumors were associated with increased luteinizing hormone levels and pheochromocytomas were most likely related to glucose malabsorption and altered calcium homeostasis. Renal tubular tumors may also have been linked to glucose malabsorption.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales/inducido químicamente , Carcinogénesis/inducido químicamente , Glucósidos/toxicidad , Neoplasias Renales/inducido químicamente , Tumor de Células de Leydig/inducido químicamente , Feocromocitoma/inducido químicamente , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Neoplasias Testiculares/inducido químicamente , Tiofenos/toxicidad , Neoplasias de las Glándulas Suprarrenales/patología , Animales , Canagliflozina , Pruebas de Carcinogenicidad , Relación Dosis-Respuesta a Droga , Glucósidos/química , Neoplasias Renales/patología , Túbulos Renales/efectos de los fármacos , Túbulos Renales/patología , Tumor de Células de Leydig/patología , Masculino , Feocromocitoma/patología , Ratas , Ratas Sprague-Dawley , Transportador 2 de Sodio-Glucosa , Relación Estructura-Actividad , Neoplasias Testiculares/patología , Tiofenos/química
16.
Ind Health ; 52(1): 66-70, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24292955

RESUMEN

Adrenal epithelioidangiosarcoma (AEA) is a rare neoplasm that accounts for less than 1% of sarcomas. Due to its rarity, it can easily be misdiagnosed, both by the clinician and the pathologist. Data on the patient's occupational history was collected and analyzed. The bibliographic data was found on the PUBMED bibliographic search site after entering the word "extrahepaticangiosarcoma". We report a case of adrenal epithelioidangiosarcoma (AEA) in a 68 yr-old Caucasian male factory worker exposed to Vinyl Chloride (VC) for 15 yr. He underwent surgery, chemotherapy and radiotherapy. Hepatic angiosarcoma is a known consequence of VC exposure, but occupational causality of extra-hepatic angiosarcoma is controversial. Extra-hepatic angiosarcomas have been reported in VC workers, but never AEA. Cancerogenic effects of VC involve all endothelial areas of the body and extra-hepatic endothelial tumors may also be caused by this substance. This is the first published report of AEA diagnosed in a worker exposed to VC.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales/inducido químicamente , Carcinógenos/toxicidad , Hemangiosarcoma/inducido químicamente , Enfermedades Profesionales/inducido químicamente , Exposición Profesional/efectos adversos , Cloruro de Vinilo/toxicidad , Neoplasias de las Glándulas Suprarrenales/patología , Anciano , Hemangiosarcoma/patología , Humanos , Masculino , Enfermedades Profesionales/patología
17.
Aging Cell ; 11(4): 675-82, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22587563

RESUMEN

Rapamycin increases lifespan in mice, but whether this represents merely inhibition of lethal neoplastic diseases, or an overall slowing in multiple aspects of aging is currently unclear. We report here that many forms of age-dependent change, including alterations in heart, liver, adrenal glands, endometrium, and tendon, as well as age-dependent decline in spontaneous activity, occur more slowly in rapamycin-treated mice, suggesting strongly that rapamycin retards multiple aspects of aging in mice, in addition to any beneficial effects it may have on neoplastic disease. We also note, however, that mice treated with rapamycin starting at 9 months of age have significantly higher incidence of testicular degeneration and cataracts; harmful effects of this kind will guide further studies on timing, dosage, and tissue-specific actions of rapamycin relevant to the development of clinically useful inhibitors of TOR action.


Asunto(s)
Envejecimiento/efectos de los fármacos , Envejecimiento/patología , Sirolimus/farmacología , Neoplasias de las Glándulas Suprarrenales/inducido químicamente , Envejecimiento/fisiología , Animales , Catarata/inducido químicamente , Endometrio/efectos de los fármacos , Endometrio/patología , Femenino , Hígado/efectos de los fármacos , Hígado/patología , Longevidad/efectos de los fármacos , Longevidad/fisiología , Masculino , Ratones , Ratones de la Cepa 129 , Ratones Endogámicos C3H , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Actividad Motora/efectos de los fármacos , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patología , Especificidad de Órganos , Sirolimus/sangre , Sirolimus/toxicidad , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Tendones/efectos de los fármacos , Tendones/patología , Testículo/efectos de los fármacos , Testículo/patología
18.
Arch Toxicol ; 86(6): 975-82, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22398986

RESUMEN

Developmental exposure to inorganic arsenic is carcinogenic in humans and mice, and adult offspring of mice exposed to inorganic arsenic can develop tumors of the lung, liver, adrenal, uterus, and ovary. It has been suggested that methylarsonous acid (MMA3+), a product of the biological methylation of inorganic arsenic, could be a key carcinogenic species. Thus, pregnant CD1 mice were provided drinking water containing MMA3+ at 0 (control), 12.5, or 25 parts per million (ppm) from gestational days 8 to 18. Tumors were assessed in groups of male or female (initial n = 25) offspring up to 2 years of age. In utero treatment had no effect on survival or body weights. Female offspring exhibited increases in total epithelial uterine tumors (control 0%; 12.5 ppm 26%; 25 ppm 30%), oviduct hyperplasia (control 4%; 12.5 ppm 35%; 25 ppm 43%), adrenal cortical adenoma at 25 ppm (control 0%; 12.5 ppm 9%; 25 ppm 26%), and total epithelial ovarian tumors (control 0%; 12.5 ppm 39%; 25 ppm 26%). Male offspring showed dose-related increases in hepatocellular carcinoma (control 0%; 12.5 ppm 12%; 25 ppm 22%), adrenal adenoma (control 0%; 12.5 ppm 28%; 25 ppm 17%), and lung adenocarcinoma (control 17%; 12.5 ppm 44%). Male offspring had unusual testicular lesions, including two rete testis carcinomas, two adenomas, and three interstitial cell tumors. Overall, maternal consumption of MMA3+ during pregnancy in CD1 mice produced some similar proliferative lesions as gestationally applied inorganic arsenic in the offspring during adulthood.


Asunto(s)
Arsénico/toxicidad , Arsenicales/efectos adversos , Carcinógenos/toxicidad , Exposición Materna/efectos adversos , Neoplasias/inducido químicamente , Complicaciones Neoplásicas del Embarazo/etiología , Efectos Tardíos de la Exposición Prenatal , Adenocarcinoma/inducido químicamente , Adenoma/inducido químicamente , Neoplasias de las Glándulas Suprarrenales/inducido químicamente , Animales , Arsénico/administración & dosificación , Carcinoma Hepatocelular/inducido químicamente , Relación Dosis-Respuesta a Droga , Femenino , Neoplasias Hepáticas/inducido químicamente , Neoplasias Pulmonares/inducido químicamente , Masculino , Ratones , Neoplasias Ováricas/inducido químicamente , Embarazo , Neoplasias Testiculares/inducido químicamente , Neoplasias Uterinas/inducido químicamente
19.
Fitoterapia ; 83(5): 843-8, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22430115

RESUMEN

Three new triterpene saponins, named asperosaponin A-C (1-3), together with seven known triterpene saponins (4-10) were isolated from the roots of Dipsacus asper. The structures of compounds 1-3 were elucidated on the basis of detailed spectroscopic analysis and chemical methods. Compounds 1-3, 6-10 had significantly protective effects in PC12 cells against the Aß(25-35) induced cytotoxicity. All the compounds isolated showed no cytotoxic activity against three human cancer cell lines, A-549, Bel-7402 and BGC-823.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales/tratamiento farmacológico , Antineoplásicos Fitogénicos/uso terapéutico , Dipsacaceae/química , Feocromocitoma/tratamiento farmacológico , Saponinas/uso terapéutico , Neoplasias de las Glándulas Suprarrenales/inducido químicamente , Péptidos beta-Amiloides , Animales , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Humanos , Estructura Molecular , Células PC12 , Fragmentos de Péptidos , Feocromocitoma/inducido químicamente , Fitoterapia , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Raíces de Plantas/química , Ratas , Saponinas/aislamiento & purificación , Saponinas/farmacología
20.
Toxicol Lett ; 209(2): 179-85, 2012 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-22230260

RESUMEN

Inorganic arsenic, an early life carcinogen in humans and mice, can initiate lesions promotable by other agents in later life. The biomethylation product of arsenic, dimethylarsinic acid (DMA), is a multi-site tumor promoter. Thus, pregnant CD1 mice were given drinking water (0 ppm or 85 ppm arsenic) from gestation day 8 to 18 and after weaning male offspring received DMA (0 ppm or 200 ppm; drinking water) for up to 2 years. No renal tumors occurred in controls or DMA alone treated mice while gestational arsenic exposure plus later DMA induced a significant renal tumor incidence of 17% (primarily renal cell carcinoma). Arsenic plus DMA or arsenic alone also increased renal hyperplasia over control but DMA alone did not. Arsenic alone, DMA alone and arsenic plus DMA all induced urinary bladder hyperplasia (33-35%) versus control (2%). Compared to control (6%), arsenic alone tripled hepatocellular carcinoma (20%), and arsenic plus DMA doubled this rate again (43%), but DMA alone had no effect. DMA alone, arsenic alone, and arsenic plus DMA increased lung adenocarcinomas and adrenal adenomas versus control. Overall, DMA in adulthood promoted tumors/lesions initiated by prenatal arsenic in the kidney and liver, but acted independently in the urinary bladder, lung and adrenal.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales/inducido químicamente , Arsénico/toxicidad , Ácido Cacodílico/toxicidad , Neoplasias Renales/inducido químicamente , Neoplasias Hepáticas/inducido químicamente , Neoplasias Pulmonares/inducido químicamente , Efectos Tardíos de la Exposición Prenatal , Animales , Femenino , Histocitoquímica , Masculino , Ratones , Embarazo , Distribución Aleatoria , Análisis de Supervivencia
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