Fibrose e outras lesÃes hepÃticas em camundongos isogÃnicos ("inbred") desnutridos e eutrÃficos, infectados com Schistosoma mansoni / Fibrosis and other hepatic lesions in undernourished and well-nourished inbred mice infected with

AUTOR(ES)
DATA DE PUBLICAÇÃO

2004

RESUMO

In chronic schistosomiasis mansoni, periovular granulomas and periportal fibrosis are the most important hepatic lesions, besides vascular changes that lead to hypertension within the portal venous system. Well-nourished Swiss outbred mice infected with Schistosoma mansoni develop lesions that mimick those found in advanced clinical forms of human intestinal schistosomiasis. For this reason and due to their easy handle and cheap cost, they are widely used as experimental model. In extensive regions of the world where schistosomiasis is endemic, undernutrition appears frequently as an associated pathology and this is also the case in Northeast Brazil, the study of the pathobiology of the vertebrate host and its nutritional status becoming of deep interest. Concerning the so-called Symmerâs fibrosis (clay pipestem fibrosis) seen in the liver of patients with advanced schistosomiasis, the lesion has been reproduced mainly in monkeys and in Swiss wellnourished mice, but it does not develop in undernourished animals. In order to study the importance of the host genetic background on the pathogenesis of this and other hepatic lesions observed in outbred mice, the present investigation aimed to characterize the hepatic changes in undernourished inbred mice in comparison with those detected in well-nourished inbred and outbred animals. Mice were infected with 30 cercariae of Schistosoma mansoni (SLM strain) by percutaneous route and sacrificed 16 weeks later by cervical dislocation. Undernutrition was induced by feeding mice with the regional basic diet (RBD) which is a lowprotein diet (7,87%) ingested by human populations residing in endemic areas of schistosomiasis in Pernambuco and other States in Northeast Brazil. Control animals were fed with NUVILAB, a standard diet for mice (22% protein). Nutritional status was studied by weekly determinations of body weights and evaluation of growth curves for all the groups throughout the experiment. Inbred mice were of BALB/c and C57BL/10 strains and Swiss otbred albino mice were used as controls. After sacrifice, the portal system was perfused for worm recovering and gross examination was performed. Liver samples were taken for histological examination, morphometry and biochemical quantificatiton of liver collagen through determination of the content of hydroxyproline. Regarding organomegaly, the highest means for liver and spleen weights belonged to well-nourished mice in comparison with undernourished animals of the same strain. Undernourished mice usually developed the lightest worm burdens when compared to well-nourished animals and also produced smaller amounts of eggs regarding the whole liver. Well-nourished groups had better growth curves than undernourished ones, the best weight gains for well-nourished outbred and the worst weight gains for undernourished inbred BALB/c mice. Spontaneous mortality was always higher for undernourished mice, mainly of the BALB/c strain, but it also happened among well-nourished animals (only 106 out of the total number of 285 mice were alive at the end of the experiment), probably due to environmental reasons and changes in the physical structure of the Animals Room of our Institution, which occurred during the experiment. According to morphometric measurements, both well-nourished and undernourished C57BL/10 inbred mice had greater amounts of hepatic collagen than the other mice strains. Biochemical differences, based upon spectrophotometry, were not statistically significant, but morphometry in this cases is considered to be a more sensitive method than spectrophotometry. Undernourished inbred mice developed smaller circumoval granulomas detected through histological examination and morphometric measurements. A lower granuloma volume density and a higher granuloma numerical density were also morphometrically detected, in comparison to well-nourished inbred mice. Both undernourished and well-nourished inbred BALB/c mice did not develop the murine pipestem-like lesion. However, four out of 21 undernourished C57BL/10 mice developed this liver lesion. This finding may be related to the type of parasitic strain since due to technical problems in the laboratory mice infections were performed with a parasitic strain (SLM strain) different from the one that had been used in previous investigations (BH strain). The hepatomegaly was related to the inflammatory infiltrates, increase of collagen deposition and protein content of the control diet (22%). Splenomegaly may be caused by hyperplasia of the mononuclear phagocytic system and venous congestion due to hemodynamic alterations within the portal region. The remaining lesions, such as periportal fatty changes of hepatic cells and scattered foci of acute coagulative necrosis by ischemia were of secondary importance in the histopathologic picture found in chronic schistosomiasis of mice. Results collected so far point to the need of further studies on the role of different types of parasitic strains in the development of the pipestem-like liver lesion in the undernourished murine model

ASSUNTO(S)

parasitic strain anatomia patologica e patologia clinica periportal fibrosis schistosomiasis mansoni camundongos swess fibrose schistosoma mansoni esquitossomose mansÃnica fibrose periportal parasitose schistosoma mansoni hepatic lesions fibrosis lesÃes hepÃticas

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