Atividade anti-inflamatória do alcaloide caulerpina em modelo murino de lesão pulmonar aguda induzida por LPS

Abstract

Natural products present in marine algae of the genus Caulerpa have been the focus of scientific investigation, due to compounds with different pharmacological activities. Therefore, the aim of this work was to evaluate the effect of the alkaloid caulerpine, obtained from marine algae of the genus Caulerpa, in a murine model of acute lung injury (ALI) induced by bacterial lipopolysaccharide (LPS). For this, we evaluated the dose of caulerpine that could best inhibit cell migration to the lung of animals stimulated with LPS. Thus, Swiss mice were treated orally with different doses of calerpine (4 Mg/Kg and 2 Mg/Kg) or with dexamethasone (1 Mg/Kg) intraperitoneally. One hour after this treatment schedule, the animals received LPS (167 µg/mL) intranasally. After 24 hours, bronchoalveolar lavage (BAL) was obtained to determine the total number of leukocytes. The treatment of mice with caulerpine, at the two doses tested, reduced the migration of leukocytes to the lung cavity in a similar way. In view of these results, the dose of 2 Mg/Kg was used for the other analyses. The same procedure was repeated to evaluate cell migration kinetics, differential cell counts, determination of total protein and pro-inflammatory cytokine levels in BAL, and histological analysis of the lung at 6, 24 or 48 hours. Caulerpine inhibited the migration of leukocytes to the lung in the ALI model at the three times analyzed, with a significant decrease in the migration of polymorphonuclear cells. It is possible to correlate this effect with the decrease in plasma proteins and proinflammatory cytokines IL-6, IL-12 and TNF-α in BAL, especially at 24 and 48 hours. Finally, the inhibition of the inflammatory process colud be followed by a decrease in tissue damage observed in the lungs of animals treated with caulerpine, where there is a lower inflammatory infiltrate, with less edema, similar to what is observed in the lungs of animals treated with dexamethasone. It is concluded that treatment with caulerpine, at a dose of 2 Mg/Kg, was effective in reducing the inflammatory process in the lung in a murine model of acute lung injury.