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1.
Regul Toxicol Pharmacol ; 85: 86-97, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28202346

RESUMEN

A new trend has been developed using vanadium and organic ligands to form novel compounds in order to improve the beneficial actions and reduce the toxicity of vanadium compounds. In present study, vanadyl trehalose was explored the oral acute toxicity, 28 days repeated dose toxicity and genotoxicity in Kunming mice. The Median Lethal Dose (LD50) of vanadyl trehalose was revealed to be 1000 mg/kg body weight in fasted Kunming mice. Stomach and intestine were demonstrated to be the main target organs of vanadyl trehalose through 28 days repeated dose toxicity study. And vanadyl trehalose also showed particular genotoxicity through mouse bone marrow micronucleus and mouse sperm malformation assay. In brief, vanadyl trehalose presented certain, but finite toxicity, which may provide experimental basis for the clinical application.


Asunto(s)
Mutágenos/toxicidad , Trehalosa/toxicidad , Compuestos de Vanadio/toxicidad , Animales , Femenino , Intestinos/efectos de los fármacos , Intestinos/patología , Dosificación Letal Mediana , Masculino , Ratones , Pruebas de Micronúcleos , Espermatozoides/anomalías , Espermatozoides/efectos de los fármacos , Estómago/efectos de los fármacos , Estómago/patología , Pruebas de Toxicidad Aguda , Pruebas de Toxicidad Subaguda
2.
Appl Biochem Biotechnol ; 180(5): 841-851, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27240663

RESUMEN

Diabetes has been cited as the most challenging health problem in the twenty-first century. Accordingly, it is urgent to develop a new type of efficient and low-toxic antidiabetic medication. Since vanadium compounds have insulin-mimetic and potential hypoglycemic activities for type 1 and type 2 diabetes, a new trend has been developed using vanadium and organic ligands to form a new compound in order to increase the intestinal absorption and reduce the toxicity of vanadium compound. In the current investigation, a new organic vanadium compounds, vanadyl rosiglitazone, was synthesized and determined by infrared spectra. Vanadyl rosiglitazone and three other organic vanadium compounds were administered to the diabetic mice through oral administration for 5 weeks. The results of mouse model test indicated that vanadyl rosiglitazone could regulate the blood glucose level and relieve the symptoms of polydipsia, polyphagia, polyuria, and weight loss without side effects and was more effective than the other three organic vanadium compounds including vanadyl trehalose, vanadyl metformin, and vanadyl quercetin. The study indicated that vanadyl rosiglitazone presents insulin-mimetic activities, and it will be a good potential candidate for the development of a new type of oral drug for type 2 diabetes.


Asunto(s)
Glucemia/metabolismo , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/tratamiento farmacológico , Homeostasis , Insulina/agonistas , Tiazolidinedionas/uso terapéutico , Vanadio/uso terapéutico , Animales , Peso Corporal/efectos de los fármacos , Modelos Animales de Enfermedad , Conducta de Ingestión de Líquido/efectos de los fármacos , Conducta Alimentaria/efectos de los fármacos , Homeostasis/efectos de los fármacos , Masculino , Metformina/farmacología , Metformina/uso terapéutico , Ratones , Quercetina/farmacología , Quercetina/uso terapéutico , Rosiglitazona , Espectrofotometría Infrarroja , Tiazolidinedionas/farmacología , Trehalosa/farmacología , Trehalosa/uso terapéutico , Vanadio/farmacología
3.
Appl Biochem Biotechnol ; 180(7): 1276-1285, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27350051

RESUMEN

5rolGLP-HV had an ideal therapeutic potential in the prevention of hyperglycemia in type 2 diabetes and delay of the thrombosis. The objective of the study was to investigate the toxicology effects of 5rolGLP-HV and guarantee its safety. In acute toxicity test, the mice were orally receiving 5rolGLP-HV at a single dose of 300 mg/kg or 2000 mg/kg. For sub-chronic toxicity study, the mice received 5rolGLP-HV at doses of 800 mg/kg or 1600 mg/kg for 9 weeks. No significant adverse effects were evident in acute and sub-chronic toxicity tests, indicating that the LD50 value is greater than 2000 mg/kg. Although the liver and kidney exhibited a little abnormal in sub-chronic toxicity study, they could recovery to normal after withdrawal 5rolGLP-HV for 2 weeks. In micronucleus assay, the mice received 5rolGLP-HV at doses of 250, 500, or 1000 mg/kg for two consecutive days. The micronucleus numbers and the polychromatic erythrocytes to normochromatic erythrocytes (PCE/NCE) ratios among 5rolGLP-HV groups were within the normal range. Similarly, sperm aberration test demonstrated that 5rolGLP-HV had no teratogenic effect on the mice sperm. In conclusion, the combined results clearly demonstrated the safety of 5rolGLP-HV and support its use as a drug to treat diabetes and thrombosis.


Asunto(s)
Péptido 1 Similar al Glucagón/toxicidad , Hirudinas/toxicidad , Péptidos/toxicidad , Proteínas Recombinantes de Fusión/toxicidad , Pruebas de Toxicidad , Administración Oral , Animales , Peso Corporal/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Femenino , Péptido 1 Similar al Glucagón/administración & dosificación , Hirudinas/administración & dosificación , Riñón/efectos de los fármacos , Riñón/patología , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Ratones , Pruebas de Micronúcleos , Péptidos/administración & dosificación , Proteínas Recombinantes de Fusión/administración & dosificación , Espermatozoides/efectos de los fármacos , Pruebas de Toxicidad Aguda , Pruebas de Toxicidad Crónica
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