Estudo farmacológico e fisiopatológico em camundongos infectados com Plasmodium berghei

Abstract

Mice experimentally infected with PZa^two c(Zu.m betg/ieZ , demonstrated the following physiopathological alterations during seven days of malarial infection: reduction in haematocrit, in- creases in parasitized erythrocytes, pulmonary edema,hipothermi_ a, formation of prostaglandin-like substances in the central nervous system, increases of plasma bradykininogen leveis up to the 6th day of infection, and decrease on the 7th day; and fina lly leukócytosis evidenced by neutrophilia, lymphocytosis and monocytosis. Total plasma protein leveis, were not altered during the course of infection. The treatment of infected animais with some pharmacolo gical antagonists, namely phenoxybenzamine, methysergide,p-chlo rophenylalanine (PCPA) and indomethacin, inhibited formation of pulmonary edema in the last 2-3 days of infection. Although tre atment with phenoxybenzamine and indomethacin potentiated malari al hypothermia on 5th, 6th and 7th days of infection, neither a serotonin receptor-blocker (methysergide) nor a serotonin synthe sis inhibitor (PCPA), significantly altered the hypothermia of the infected animais. When normal animais were injected intravenously with supernatant obtained by incubating leukocytes from infected do nors (7th day of infection), they showed a significant fali in body temperature, similar to that observed in P. betgheZ-infected animais. These results showed that: a) The observed physiopathological alterations of mice infected with P. have involvement of endogenous media- tors namely, cathecolamines, serotonin, prostaglandins and pias ma kinins. b) Together with endogenous mediators, leukocytes have participated in the generation and maintenance of these altera tions. '