RESUMEN
This study aimed to evaluate and compare the effects of co-treatment with purified annatto oil (PAO) or its granules (GRA, Chronic®) with that of testosterone on the orchiectomy-induced osteoporosis in Wistar rats. After surgery, rats were treated from day 7 until day 45 with testosterone only (TES, 7 mg/kg, IM) or TES + PAO or GRA (200 mg/kg, p.o.). The following parameters were evaluated: food/water intake, weight, HDL, LDL, glucose, triglycerides (TG), total cholesterol (TC), alkaline phosphatase levels, blood phosphorus and calcium contents, femur weight, structure (through scanning electron microscopy), and calcium content (through atomic absorption spectrophotometry). Our results show that orchiectomy could significantly change the blood lipid profile and decrease bone integrity parameters. Testosterone reposition alone could improve some endpoints, including LDL, TC, bone weight, and bone calcium concentration. However, other parameters were not significantly improved. Co-treatment with PAO or GRA improved the blood lipid profile and bone integrity more significantly and improved some endpoints not affected by testosterone reposition alone (such as TG levels and trabeculae sizes). The results suggest that co-treatment with annatto products improved the blood lipid profile and the anti-osteoporosis effects of testosterone. Overall, GRA had better results than PAO.
Asunto(s)
Bixaceae/química , Carotenoides/química , Fémur/efectos de los fármacos , Lípidos/sangre , Orquiectomía , Osteoporosis/sangre , Osteoporosis/etiología , Extractos Vegetales/química , Aceites de Plantas/farmacología , Testosterona/farmacología , Animales , Peso Corporal/efectos de los fármacos , Conducta de Ingestión de Líquido/efectos de los fármacos , Conducta Alimentaria/efectos de los fármacos , Fémur/ultraestructura , Masculino , Sustancias Protectoras/farmacología , Ratas WistarRESUMEN
Artemisinin is an antimalarial compound isolated from Artemisia annua L. that is effective against Plasmodium falciparum. This paper proposes the development of new antimalarial derivatives of artemisinin from a SAR study and statistical analysis by multiple linear regression (MLR). The HF/6-31G** method was used to determine the molecular properties of artemisinin and 10 derivatives with antimalarial action. MEP maps and molecular docking were used to study the interface between ligand and receptor (heme). The Pearson correlation was used to choose the most important properties interrelated to the antimalarial activity: Hydration Energy (HE), Energy of the Complex (Ecplex), bond length (FeO1), and maximum index of R/Electronegativity of Sanderson (RTe+). After the Pearson correlation, 72 MLR models were built between antimalarial activity and molecular properties; the statistical quality of the models was evaluated by means of correlation coefficient (r), squared correlation coefficient (r(2)), explained variance (adjusted R(2)), standard error of estimate (SEE), and variance ratio (F), and only four models showed predictive ability. The selected models were used to predict the antimalarial activity of ten new artemisinin derivatives (test set) with unknown activity, and only eight of these compounds were predicted to be more potent than artemisinin, and were therefore subjected to theoretical studies of pharmacokinetic and toxicological properties. The test set showed satisfactory results for six new artemisinin compounds which is a promising factor for future synthesis and biological assays.
Asunto(s)
Antimaláricos/farmacología , Artemisininas/farmacología , Modelos Moleculares , Plasmodium falciparum/efectos de los fármacos , Animales , Antimaláricos/química , Antimaláricos/farmacocinética , Artemisininas/química , Artemisininas/farmacocinética , Células CACO-2 , Perros , Diseño de Fármacos , Humanos , Ligandos , Modelos Lineales , Células de Riñón Canino Madin Darby , Modelos Estadísticos , Simulación del Acoplamiento Molecular , Relación Estructura-Actividad CuantitativaRESUMEN
The mineral exploration in the Amazon, has determined impacts for the environment and for the populations exposed to different agents of the production process. The extraction and the beneficiation developed in the state of Amapa left environmental damages and issues that influence the population´s health, such as contamination by metals. Researches have shown that some forms of metals are toxic; causing neurological and genetic complications. The present work considers the toxicological evaluation a fundamental prerequisite in the identification of potential damages to the health. Accordingly, the study´s objective is the investigating of the toxic effects through laboratory analysis in a population group of the Elesbao district in Santana-AP municipality exposed to residues of minerals and metals. In this way, the amount of metals in Elesbao´s water region was evaluated by spectrophotometer, hematological and biochemical tests were accomplished for laboratory evaluation. The paired t-test was applied for statistical evaluation with a significance of 5% (p <0.05). It was concluded that iron and manganese are present in high concentrations in the region water. Hematological and biochemical exams presented statistically relevant alterations. Significant differences in the morphology of the cells were detected by microscopic analysis. This study demonstrates the importance of the investigation of sources of metal exposure and preventing the elimination and minimization of the risks of adverse effects to excessive exposure to multiple metals.(AU)