ABSTRACT
Bioassay-guided fractionation of an ethanolic extract of Ochrosia borbonica led to the isolation of two known pyridocarbazole alkaloids, ellipticine (1) and 9-methoxyellipticine (2), and six known monoterpenoid indole alkaloids (3-8). Lipid-lowering assay in 3T3-L1 cell model revealed that 1 and 2 could significantly inhibit the lipid droplet formation (EC = 0.41 and 0.92 μmol·L, respectively) and lower triglyceride levels by 50%-60% at the concentration of 1 μmol·L, being more potent than the positive drug luteolin (EC = 2.63 μmol·L). A mechanistic study indicated that 1 and 2 could intercalate into supercoiled DNA, which consequently inhibited the mitotic clonal expansion of 3T3-L1 cells at the early differentiation phase, leading to the retardance of following adipogenesis and lipogenesis. These findings suggest that 1 and 2 may serve as promising leads for further development of anti-obesity drugs.
ABSTRACT
Os hipolipemiantes são medicamentos de eficácia comprovada no tratamento dos distúrbios do metabolismo dos lipídeos. Essas drogas reduzem a morbidade e a mortalidde em eventos cardiovasculares de forma notória. A suspeita de que esses agentes podem aumentar o risco de câncer tem sido questionada desde o início de seu uso, gerando intensos debates e reanálises de ensaios clínicos sobre o assunto. Recentemente, os resultados do estudo Sinvastatin and Ezetimibe in Aortic Stenosis (SEAS) despertaram novo interesse por esse tema, pois os pacientes submetidos a terapia hipolipemiante intensiva tiveram número aumentado de câncer em comparação com o grupo controle. Este artigo visa a revisar os estudos em busca de evidência sobre associação do uso de hipolipemiantes e baixos níveis de colesterol com incidência de câncer. Até o momento não há evidências concretas de meta-análises, seja com estatinas ou, mais recentemente, com ezetimiba, que indiquem que esses medicamentos induzam o aparecimento de neoplasias ou que elevem o risco de mortalidade pelo câncer.
The efficacy of lipid-lowering agents in the treatment of lipid metabolism disorders is well established. These drugs markedly reduce morbidity and mortality in cardiovascular events. The hypothesis that lipid-lowering drugs might increase the risk of cancer has been questioned from the very beginning of their use and has been subject of intense debate and several attempts to reanalyze clinical trial data. Recently, the results of the Simvastatin and Ezetimibe in Aortic Stenosis Study (SEAS) has sparked new interest on this issue, since patients undergoing intense lipid-lowering therapy had a higher rate of cancer than the control group. This article gives an overview of the clinical evidence on the association of lipid-lowering drugs and low cholesterol levels with the incidence of cancer. So far there are no clear evidences from metanalyses, whether with statins or more recently with ezetimibe, indicating that these drugs induce the development of cancer or increase the risk of mortality due to cancer.
Subject(s)
Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Neoplasms/complications , Lipid Metabolism Disorders/therapyABSTRACT
Mixed dyslipidemia is a common lipid disorder.Coadministrating hypolipidemic drugs for the treatment of mixed dyslipidemia has shown functions,such as enhancement of reaching lipid goals,reduction of side effects associated with increasing dosage.The usual combination is applied to add another agent on statins,including fibrates,niacin or ezetimibe.Special attention should be paid to the safety of such combination therapy.
ABSTRACT
OBJECTIVE: To determine the histopathological effect of statins, fibrates and its combination in rat nervesMETHODOLOGY: This is a pilot experimental study. Four male albino rats were used in this study. Each rat was given therapeutic doses of simvastatin alone, gemfibrozil alone, gemfibrozil and simvastatin combination and placebo. On day 21, the sciatic nerve was harvested for histopathologic examinationRESULTS: Although not marked, the combination of simvastatin and gemfibrozil produced more axonal degeneration than did simvastatin alone or gemfibrozil alone. Axonal degeneration was documented on teased nerve fibers and epon cross sectionsCONCLUSION: The use of lipid lowering agents may induce peripheral neuropathy Recommendation: This pilot study serves as rationale to proceed with an experiment not only to document neuropathy but also correlate the possible association of the pathomechanism of myotoxicity and neurotoxicity of lipid lowering agents.