Caffeine attenuates liver damage and improves neurologic signs in a rat model of hepatic encephalopathy.

INTRODUCTION AND AIMS: Cirrhosis is the common outcome of liver diseases. It can be decompensated and lead to the development of complications, such as encephalopathy. Hyperammonemia that develops due to liver dysfunction is etiopathologically related to hepatic encephalopathy. Caffeine increases the activity of the urea cycle in the liver, augmenting ammonia degradation. By antagonizing adenosine receptors, it also has a hepatoprotective effect, impeding the formation of fibrosis, as well as having a stimulating effect on the central nervous system. The present study analyzed the effects of caffeine on the progression of cholestatic liver fibrosis and hepatic encephalopathy. MATERIALS AND METHODS: An experimental model of cholestatic liver fibrosis, through common bile duct ligature, and of hepatic encephalopathy, through the administration of a high-protein diet, was constructed. Male Wistar rats (n=32) were equally divided into 4 groups. The experiment lasted 28 days, with the administration of 50mg/kg/day of caffeine. Laboratory tests, histologic analyses of the liver and encephalon, open field tests (OFTs), and daily behavioral analyses were carried out. RESULTS: The ligated animals treated with caffeine had lower mean transaminase levels and improved histologic aspects of the liver and encephalon. The untreated ligated animals were clearly lethargic and apathetic at the last week of the experiment, confirmed by reduced exploratory activity during the OFT. CONCLUSION: Caffeine improved the microarchitecture of the liver and encephalon of the cirrhotic animals and prevented the decrease in exploratory behavior of the animals during the OFT.

Quantification of Trypanosoma cruzi in the heart, lymph nodes and liver of experimentally infected mice, using limiting dilution analysis.

Limiting dilution analysis was used to quantify Trypanosoma cruzi in the lymph nodes, liver and heart of Swiss and C57Bl/10 mice. The results showed that, in Swiss and Bl/10 mice infected with T. cruzi Y strain, the number of parasites/mg of tissue increased during the course of the infection in both types of mice, although a greater number of parasites were observed in heart tissue from Swiss mice than from Bl/10. With regard to liver tissue, it was observed that the parasite load in the initial phase of infection was higher than in heart. In experiments using T. cruzi Colombian strain, the parasite load in the heart of Swiss and Bl/10 mice increased relatively slowly, although high levels of parasitization were nonetheless observable by the end of the infection. As for the liver and lymph nodes, the concentration of parasites was lower over the entire course of infection than in heart. Both strains thus maintained their characteristic tissue tropisms. The limiting dilution assay (LDA) proved to be an appropriate method for more precise quantification of T. cruzi, comparing favorably with other direct microscopic methods that only give approximate scores.

Participation of endothelial cells in murine schistosomiasis.

The endothelial cells participate in the morphological events occurring during murine schistosomiasis, taking part in the development of hepatic periovular granuloma. The cells also show an increase in the expression of Factor VIII-related antigen in the portal vessels and hepatic sinusoids during the infection. Endothelial cells are suggested to play an important role in the pathogenesis of the disease and in the balance of the coagulant-anticoagulant mechanisms which favor the intravascular survival of the parasites.

Participation of endothelial cells in murine schistosomiasis

The endothelial cells participate in the morphological events occuring during murine schistosomiasis, taking part in the development of hepatic periovular granuloma. The cells also show an increase in the expression of Factor WIII - related antigen in the portal vessels and hepatic sinusoids during the infection. Endothelial cells are suggested play an important role in the pathogenesis of the disease and in the balance of the coagulant - anticoagulant mechanisms which favor the intravascular survial of the parasites

Eosinophils favor the passage of eggs to the intestinal lumen in schistosomiasis.

The release of Schistosoma mansoni eggs to the intestinal lumen of Swiss Webster albino mice is dependent on the peri-ovular inflammatory cells, especially eosinophils. The cells corrode the epithelial basal membrane and provide an easily penetrated environment for the eggs, allowing them to be passively expelled by intestinal peristalsis.

Congenital and nursing effects on the evolution of Schistosoma mansoni infection in mice.

Modification of the immune response to schistosomal infection in children or offspring born to mother R infected with Schistosoma mansoni has been demonstrated in human and in experimental schistosomiasis. One of the hypothesis to explain this fact could be the transfer of circulating antigens and antibodies from mother to foetus through the placenta or from mother to child by milk. The results of this spontaneous transference are controversial in the literature. In an attempt to investigate these questions, we studied one hundred and twenty offspring (Swiss mice), sixty born to infected-mothers (group A) and sixty born to non-infected mothers (group B). These were percutaneously infected with 50 cercariae/mouse, and divided in six sub-groups (20 mice/sub-group), according to the following schedule: after birth (sub-groups A.I and B.I), 10 days old (sub-groups A.II and B.II) and 21 days old (sub-groups A.III and B.III). After the exposure period, the young mice returned to their own mothers for nursing. Six weeks later, the mice were killed. We obtained the following results: 1) There is transference of antibody to cercariae (CAP), adult worms (SWAP) and egg antigens (SEA) from the infected mothers to the offspring, probably through placenta and milk; 2) Offspring born to infected mothers exhibit much less coagulative hepatic necrosis and show a lower number of eggs in the small intestine and a less intense and predominant exsudative stage of the hepatic granulomas when compared with the exsudative-productive stage of the control groups. The findings suggest that congenital and nursing factors can interfere on the development of the schistosomiasis infection, causing an hyporesponse to the eggs.

"In vivo" kinetics of eosinophils and mast cells in experimental murine schistosomiasis.

During the schistosomiasis infection there is a "dance of the cells", varying from site to site and related to the time of infection. 1--Eosinophil levels exhibit a bimodal pattern, with the first peak related to the egg deposition and maturation and increased Kupfferian hyperplasia; the second peak precedes the death of some adult worms; 2--The peritoneal eosinophilic levels are inversely proportional to the blood eosinophilic levels; 3--Eosinopoiesis in the bone marrow begins at day 40, reaching the highest levels at day 50 and coincides with hepatic eosinophilic and neutrophilic metaplasia; 4--Peritoneal mast cell levels present a bimodal pattern similar to the blood eosinophils, and inverse to the peritoneal eosinophils. They also show a cyclic behaviour within the hepatic and intestinal granulomas. Integral analysis of the events related to the eosinophils in the blood, bone marrow, peritoneal cavity and hepatic and intestinal granulomas allows the detection of two important eosinophilic phases: the first is due to mobilization and redistribution of the marginal pool and the second originates from eosinophilic production in the bone marrow and liver. The productive phase is characterized by an increase in the number of eosinophils and monocyte/macrophages, and a decrease in neutrophils and stabilization of megakariocytes and erithroid lineages.

In vivo kinetics of eosinophils and mast cells in experimental murine Schistosomiasis

During the schistosomiasis infection there is a [quot ]dance of the cells[quot ], varying from site to site and related to the time of infection. 1 - Eosinophil levels exhibit a bimodal pattern, with the first peak related to the egg deposition and maturation and increased Kupfferian hyperplasia; the second peak precedes the death of some adult worms; 2 - The peritoneal eosinophilic levels are inversely proportional to the blood eosinophilic levels; 3 - Eosinopoiesis in the bone marrow begins at day 40, reaching the highest levels at day 50 and coincides with hepatic eosinophilic and neutrophilic metaplasia; 4 - Peritoneal mast cell levels present a bimodal pattern similar to the blood eosinophils, and inverse to the peritoneal eosinophils. They also show a cyclic behaviour within the hepatic and intestinal granulomas. Integral analysis of the events related to the eosinophils in the blood, bone marrow, peritoneal cavity and hepatic and intestinal granulomas allows the detection of two important eosinophilic phases: the first is due to mobilization and redistribution of the marginal pool and the second originates from eosinophilic production in the bone marrow and liver. The productive phase is characterized by an increase in the number of eosinophils and monocyte/macrophages, and a decrease in neutrophils and stabilization of megakariocytes and erithroid lineages.

Congenital and nursing effects on the evolution of Schistosoma mansoni infection in mice

Modification of the immune response to schistosomal infection in children or offspring born to mother R infected with Schistosoma mansoni has been demonstrated in human and in experimental schistosomiasis. One of the hypothesis to explain this fact could be the transfer of circulating antigens and antibodies from mother to foetus through the placenta or from mother to child by milk. The results of this spontaneous transference are controversial in the literature. In an attempt to investigate these questions, we studied one hundred and twenty offspring (Swiss mice), sixty born to infected-mothers (group A) and sixty born to non-infected mothers (group B). These were percutaneously infected with 50 cercariae/mouse, and divided in six sub-groups (20 mice/sub-group), according to the following schedule: after birth (sub-groups A.I and B.I), 10 days old (sub-groups A.II and B.II) and 21 days old (sub-groups A.III and B.III). After the exposure period, the young mice returned to their own mothers for nursing. Six weeks later, the mice were killed. We obtained the following results: 1) There is transference of antibody to cercariae (CAP), adult worms (SWAP) and egg antigens (SEA) from the infected mothers to the offspring, probably through placenta and milk; 2) Offspring born to infected mothers exhibit much less coagulative hepatic necrosis and show a lower number of eggs in the small intestine and a less intense and predominant exsudative stage of the hepatic granulomas when compared with the exsudative-productive stage of the control groups. The findings suggest that congenital and nursing factors can interfere on the development of the schistosomiasis infection, causing an hyporesponse to the eggs.