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      Efectos del policosanol en los modelos de pleuresía inducida por carragenina y granuloma por algodón Translated title: Effects of policosanol on carrageenan-induced pleurisy and cotton pellet granuloma models

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          Abstract

          Introducción: el policosanol, mezcla de alcoholes alifáticos primarios superiores purificada de la cera de caña, inhibe la actividad de la cicloxigenasa-1 (COX-1) in vitro, efecto que pudiera sustentar su acción antiagregante plaquetaria. Sin embargo, sus posibles efectos en modelos experimentales de inflamación no se habían investigado. Objetivo: determinar el efecto antinflamatorio in vivo del policosanol en un modelo de inflamación aguda (pleuresía por carragenina) y crónico (granuloma por algodón). Métodos: se distribuyeron las ratas Sprague Dawley en siete grupos para el modelo de inflamación aguda: un control negativo (vehículo) y seis a los que se les indujo la inflamación: un control positivo (vehículo), cuatro tratados con policosanol (50-800 mg/kg) y uno con aspirina (100 mg/kg). Se cuantificaron a las 5 h el volumen de exudado pleural, la concentración de proteínas y actividad de la enzima mieloperoxidasa. Se distribuyeron las ratas en seis grupos para el modelo crónico: un control (vehículo), cuatro tratados con policosanol (50-800 mg/kg) y uno con aspirina (100 mg/kg). Se extrajo el granuloma para determinar los pesos húmedo y seco seis días después de implantado el pellet. Resultados: dosis orales únicas de policosanol (200, 400 y 800 mg/kg) redujeron significativa y moderadamente el volumen, la actividad de la enzima mieloperoxidasa (» 12 %) y la concentración de proteínas (» 20 %) del exudado pleural, mientras la aspirina redujo estos indicadores en un 35,3, 19,9 y 19,1%, respectivamente. La administración oral de policosanol (400 y 800 mg/kg) durante 6 días disminuyó significativa y moderadamente el peso húmedo del granuloma (16,4 y 16,2 %), y el peso seco (28,4 y 34,4 %). La aspirina 100 mg/kg redujo estas variables en un 18,5 % (peso húmedo) y 34,4 % (peso seco). Ambos tratamientos produjeron mayores reducciones del peso seco que del peso húmedo del granuloma. Conclusiones: la administración oral de policosanol produjo un moderado efecto antinflamatorio in vivo en modelos de inflamación aguda y crónica.

          Translated abstract

          Introduction: policosanol, a mixture of higher aliphatic alcohols purified from sugarcane wax, inhibits cyclooxygenase-1 (COX-1) activity in vitro, an effect that could support its anti-platelet action. Its putative effects on experimental models of inflammation had not been yet investigated. Objective: to determine the in vivo effect of policosanol on acute (carrageenan-induced pleurisy) and chronic inflammation (cotton-pellet granuloma) in vivo models. Methods: in the acute model, rats were randomly distributed into seven groups: a negative vehicle control, and six with carrageenan-induced pleurisy: a positive control (vehicle), four treated with policosanol (50-800 mg/kg) and one with aspirin (100 mg/kg). Five hours later, volume of pleural exudate, protein concentration and myeloperoxidase activity were quantified. For the chronic model, rats were distributed into six groups: a control (vehicle), four treated with policosanol (50-800 mg/kg) and one group with aspirin (100 mg/kg). The cotton pellet was implanted and six days after treatment, it was extracted to determine the dry and the wet weights. Results: single oral doses of policosanol (200, 400 and 800 mg/kg) reduced significantly and moderately the volume (» 20 %), the myeloperoxidase activity (» 12 %) and the protein concentration (» 20 %) in pleural exudates, whereas aspirin 100 mg/kg decreased significantly these indicators by 35.3, 19.9 and 19.1 %, respectively. Oral administration of policosanol (400 and 800 mg/kg) for 6 days reduced significantly and moderately the wet (16.4 and 16.2 %, respectively) and dry (28.4 and 34.4 %, respectively) granuloma weights. Treatment with 100 mg/kg aspirin reduced these variables by 18.5 % (wet weight) and 34.4 % (dry weight), respectively. Both treatments reduced the dry more than the wet granuloma weight. Conclusion: oral administration of policosanol produced a moderate anti-inflammatory effect in vivo on models of acute and chronic inflammation.

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          Most cited references33

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          Myeloperoxidase: molecular mechanisms of action and their relevance to human health and disease.

          Myeloperoxidase (MPO) is a heme-containing peroxidase abundantly expressed in neutrophils and to a lesser extent in monocytes. Enzymatically active MPO, together with hydrogen peroxide and chloride, produces the powerful oxidant hypochlorous acid and is a key contributor to the oxygen-dependent microbicidal activity of phagocytes. In addition, excessive generation of MPO-derived oxidants has been linked to tissue damage in many diseases, especially those characterized by acute or chronic inflammation. It has become increasingly clear that MPO exerts effects that are beyond its oxidative properties. These properties of MPO are, in many cases, independent of its catalytic activity and affect various processes involved in cell signaling and cell-cell interactions and are, as such, capable of modulating inflammatory responses. Given these diverse effects, an increased interest has emerged in the role of MPO and its downstream products in a wide range of inflammatory diseases. In this article, our knowledge pertaining to the biologic role of MPO and its downstream effects and mechanisms of action in health and disease is reviewed and discussed.
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            Statins and inflammation: an update.

            Randomized trials have suggested that the beneficial effects of statins could extend to mechanisms beyond cholesterol reduction. Investigations have shown that statins are associated with reduced plasma markers of inflammation, reduced T-cell and monocyte activation, and reduced blood clotting. These effects could be explained by the inhibition of L-mevalonic acid synthesis, thus affecting cell-signalling pathways. However, it has been difficult to evaluate whether the nonlipid effects of statins translate into clinically meaningful outcomes. Inflammation, as measured by C-reactive protein (CRP), has been established as an independent cardiovascular risk factor, even in persons with low-density lipoprotein (LDL)-cholesterol. Statins have anti-inflammatory effects, and lower CRP. Reducing both LDL-cholesterol and CRP is important in order to decrease the risk of cardiovascular events. Statins significantly reduce the risk of venous thrombosis. It is probable that this effect goes beyond lipid lowering. The clinical benefit of statin therapy in infectious diseases remains to be determined by randomized controlled trials. Statins have anti-inflammatory properties that are clinically important in lowering cardiovascular risk. It is probable, but not definitely proven, that some of the benefits of statins are due to their nonlipid effects.
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              Policosanol

              R Mas, R Mas (2000)
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Journal
                far
                Revista Cubana de Farmacia
                Rev Cubana Farm
                Editorial Ciencias Médicas (Ciudad de la Habana )
                1561-2988
                December 2013
                : 47
                : 4
                : 492-501
                Article
                S0034-75152013000400009
                5f3d1518-ea25-493a-94c5-7cb15da0d42e

                http://creativecommons.org/licenses/by/4.0/

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                SciELO Cuba

                Self URI (journal page): http://scielo.sld.cu/scielo.php?script=sci_serial&pid=0034-7515&lng=en
                Categories
                PHARMACOLOGY & PHARMACY

                Pharmacology & Pharmaceutical medicine
                policosanol,granuloma,pleurisy,carrageenan,myeloperoxidase,pleuresía,carragenina,mieloperoxidasa

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