RESUMO
Myocardial infarction [MI] is a common presentation of the ischemic heart disease. Lavandula angustifolia is an herbaceous plant with antioxidative effects. This study was designed to investigate the cardioprotective effects of lavandula angustifolia essential oil against isoproterenol-induced MI in rats. The dried sample was subjected to hydrodistillation by using a Clevenger and the oils were dried over anhydrous Na[2]SO[4]. Male Wistar rats were assigned to 6 groups of control, sham, isoproterenol and treatment with 5, 10, 20 mg/Kg of the essential oil. MI was induced by subcutaneous injection of Isoproterenol [100 mg/Kg] for 3 consecutive days at an interval of 24 h. The essential oil was given intraperitoneally every 24 h started at MI induction. Following anesthesia, hemodynamic parameters were measured. After sacrificing the animals, the hearts were removed to measure the heart to body weight ratio and histopathological examination. Myeloperoxidase [MPO] and Malondialdehyde [MDA] were measured in heart tissues for evaluating the activity of neutrophils and lipid peroxidation, respectively. The essential oil amended ECG pattern by suppressing ST-segment elevation and increasing R-amplitude. 10 mg/Kg of the essential oil significantly decreased heart to body weight ratio [P<0.001] and the elevation of MDA and MPO in myocardium, it also increased dp/dtmax from 2793 +/- 210 to 4488 +/- 253 mmHg/sec [P<0.001], and 20 mg/Kg of it significantly lowered LVEDP from 14 +/- 3.43 to 4.3 +/- 0.83 mmHg [P<0.001].The results demonstrated that L. angustifolia protects myocardium against isoproterenol-induced MI that it could be related to its antioxidant properties
Assuntos
Animais de Laboratório , Óleos Voláteis , Cardiotônicos , Isoproterenol , Infarto do Miocárdio , Ratos WistarRESUMO
Silicon is the element very similar to carbon, and bioactive siliconized compounds have therefore received much attention. Siliconization of a compound enhances its biological activities. In the present study the hypolipidemic effect and toxicity of clofibrate and its siliconized analog, silafibrate, were compared. The experiments were performed in hypercholesterolemic Wistar rats. Animals received high fat diet with 62.75% normal chow, 2% cholesterol, 0.25% cholic acid, 15% lard oil, 10% wheat flour and 10% sucrose. Silafibrate[40 mg/kg/day] produced a predominant reduction in the serum levels of total cholesterol [28.4%, p < 0.001], triglycerides [62%, p < 0.0001] and low-density lipoproteins [27%, p < 0.001] being more effective than the reference drug clofibrate [20%, 40%, 14.5%; p < 0.05]. Similarly, it increased the total antioxidant levels in serum by 40% [p < 0.05]. Simultaneously, treatment with silafibrate also reduced the malondialdehyde [MDA] concentration by 41% [p < 0.05]. LD[50] of silafibrate, given orally, was greater than 2000 mg/kg body weight in albino mice while LD[50] for clofibrate was calculated to be 1220 mg/kg. Thirty-day subacute toxicity was also evaluated with oral daily dose at 25, 50 and 100 mg/kg body weight in Wistar rats. No significant changes in body weight, food intake, behavior, mortality, hematology, blood biochemistry, vital organ weight were detected. The results of this study indicate that the effectiveness and safety of the hypolipidemic drug, clofibrate, were enhanced remarkably by replacing chlorine atom in its phenoxy ring with trimethylsilyl
Assuntos
Animais , Masculino , Clofibrato/análogos & derivados , Hipolipemiantes/farmacologia , Ratos Wistar , Colesterol na Dieta , Lipoproteínas/sangueRESUMO
A growing body of preclinical data indicates that statins may possess antineoplastic properties; however, some studies have raised the possibility that statins may also have carcinogenic potential. An air pouch model was used for angiogenesis. Single or multiple applications of croton oil on the back of Swiss albino mice with or without initiation by dimethylbenz[a]antheracene [DMBA] were used to evaluate the skin tumorgenesis, ultrastructural and histological alterations. Atorvastatin [orally, 10 mg/kg/day] produced a significant [P<0.05] reduction in angiogenesis. Concurrent administration of mevalonate reversed the antiangiogenic effect of atorvastatin. However, local injection of atorvastatin [200 micro g] into the pouches induced a significant [P<0.5] increase in angiogenesis that was not reversed by co-administration of mevalonate. The disturbance of cell polarity, inflammatory response, thickness of epidermal layer, and mitotic index induced by croton oil were inhibited markedly and dose-dependently [P<0.001] by pre-treatment with atorvastatin. In spite of the strong anti-inflammatory and anti-proliferative effects of atorvastatin on epidermal cell proliferation, it was identified that the same doses of atorvastatin in DMBA-initiated and croton oil-promoted skin tumorgenesis in mice increased the incidence of tumors and their conversion into malignant carcinoma. The reasons for these discrepancies remain unclear, and could be related to ambivalent effects of atorvastatin on angiogenesis or to specific differences in the experimental conditions. It is suggested that the pro-angiogenic effect of the drug, which could be responsible for promotion of skin tumors, is independent of the 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibition that can be mediated directly by atorvastatin
Assuntos
Animais de Laboratório , Indutores da Angiogênese , Proliferação de Células , Neoplasias , Modelos Animais , Camundongos , CarcinogêneseRESUMO
Fibrates, as hypolipidemic drugs known as agonists of peroxisome proliferator-activated receptors, diminish inflammatory responses. Studies have shown that incorporation of a silicon atom into a drug structure improves its pharmacological potency, modifies its selectivity toward a given target, or changes its metabolic rate, in addition to increasing the lipophilicity of the compounds. A siliconized analog of clofibrate, ethyl-2-methyl-2-[4-[trimethylsilyl]phenoxy]propionate was synthesized, whereby the chlorine atom in the phenoxy ring was replaced by a trimethylsilyl group. The anti-inflammatory effects of the siliconized analog [silafibrate] were evaluated in an air-pouch model of inflammation and compared with those of clofibrate. Oral administration of both drugs produced a significant anti-inflammatory action by reducing carrageenan induced pouch leukocyte recruitment, exudates production, and granulated tissue weight. The silicon isostere of clofibrate has improved anti-inflammatory properties
RESUMO
Statins have been shown to exert "pleiotropic effects" independent of their cholesterol lowering actions that include anti-inflammatory properties. We show in this study that atorvastatin dependent on the way of administration may exert anti- or pro- inflammation effects. Carrageenan-induced rat paw edema and mouse air-pouch as inflammatory models were used in this study. Animals were received statins orally prior to induction of inflammation by injection of carrageenan into rat paw or the pouch. The local effect of atorvastatin was determined by injection of the drug into the pouch. Oral administration of statins reduced both the maximal edema response and neutrophils infiltration in the inflammation zone. Lovastatin had the lowest and atorvastatin had the greatest effects. Also, in the mouse air-pouch model oral treatment by atorvastatin produced a very significant [p < 0.0001] reduction in carrageenan-induced pouch leukocyte recruitment and exudates production. Concurrent administration of mevalonate revers ed the anti-inflammatory effect of atorvastatin. However, local injection of atorvastatin into the pouch induced a dose depend and significant increase in leukocyte recruitment into the pouch that was not reversed by co-administration of mevalonate. This study shows that atorvastatin dependent on the way of administration has both pro- and anti- inflammatory properties. Contrary to anti-inflammatory effects, the pro-inflammatory responses are independent of HMG CoA reductase inhibition and can be mediated directly by atorvastatin