Navegando por Autor "KAUFFMANN, Nayara"

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Acesso aberto (Open Access)
A infecção por Plasmodium berghei (ANKA) induz um quadro de encefalopatia hepática em modelo murino de malária não complicada
(Universidade Federal do Pará, 2024-02) KAUFFMANN, Nayara; SILVA, Anderson Manoel Herculano Oliveira da; http://lattes.cnpq.br/8407177208423247; https://orcid.org/0000-0003-4022-8096; OLIVEIRA, Karen Renata Herculano Matos; http://lattes.cnpq.br/3032008039259369
Introduction. The main changes in hepatocellular dysfunction associated with malaria are liver failure, hepatosplenomegaly and increased liver enzymes. Several studies have already elucidated that such liver changes can be caused by increased ammonia levels, which can consequently lead to dysfunction in the central nervous system (CNS), causing hepatic encephalopathy, culminating in an increase in the inflammatory response, cerebral edema, deregulation of neurotransmitters and cognitive and locomotor changes. Objective: To characterize possible changes in the central nervous system resulting from liver injury induced by Plasmodium berghei ANKA infection in a murine model of uncomplicated malaria. Methodology. For this, mice of the Balb-c lineage (20- 25g) were used between 45-54 postnatal days (CEUA nº 2229290317), inoculated with ~106 parasitized erythrocytes intraperitoneally. The experimental design was divided into two parts: Firstly, the survival curve, parasitemia, body mass, clinical signs, hepatic and histological changes, neurochemistry, presence of cerebral edema, vascular extravasation, inflammatory response, behavioral changes and quantification of blood levels were characterized. ammonia in the control and PbA groups. Subsequently, a treatment with lactulose was carried out to verify whether the changes found in the previous experiments were due to the increase in ammonia levels in the animals' brains. For this purpose, the groups were divided into: control group, lactulose 3mg/kg, PbA and PbA+lactulose 3mg/kg, in which the survival curve, parasitemia and locomotor activity were evaluated using the SHIRPA protocol. The results were expressed as mean+standard deviation. ANOVA (one way) was performed, post Tukey test, considering p<0.05 as significant. Results. Our data demonstrated that the PbA group presented changes in liver functions such as increased levels of AST and ALP, BT and BD, morphological changes such as hepatosplenomegaly, in addition to histological changes showing inflammatory infiltrate, deposition of malarial pigment and Kupffer cell hyperplasia, thus demonstrating a picture of liver failure. After characterizing the liver injury, we sought to understand whether these changes could generate impairment in the CNS, which we observed cognitive and motor impairment, in addition to changes in the levels of the neurotransmitters GABA and glutamate, accompanied by an increase in the inflammatory response, cerebral edema and dysfunction in the liver. blood-brain barrier. Once liver failure was demonstrated and, consequently, the presence of cognitive and behavioral changes, we sought to evaluate ammonia levels in the brains of control and PbA animals in the initial phase of infection. In this sense, the quantification of ammonia levels showed an increase on the 10th d.p.i., in brain tissue when compared to the control group, in which the levels were within expectations in relation to locomotor activity, when applying the protocol in the infected and treated group with lactulose, it was possible to observe that the PbA group showed changes in motor behavior, when compared to the control group. In contrast, the PbA+Lactulose 3mg/kg group showed an attenuation of cognitive and behavioral changes, showing that therapy with lactulose can attenuate the cognitive condition regarding motor behavior, muscle strength and tone, reflexes, and sensory function. Conclusion. We conclude that liver failure causes hepatic encephalopathy in a murine model of uncomplicated malaria, which culminates in changes in the central nervous system, by increasing ammonia levels in the brain, and by sequestering ammonia with the help of treatment. with lactulose at a dose of 3mg/kg, it can attenuate the neurological damage of animals with uncomplicated malaria, demonstrating that the behavioral changes come from a condition of hepatic encephalopathy, caused by increased levels of ammonia in the cortex of infected animals.
Acesso aberto (Open Access)
O tratamento com glutationa potencializa o dano hepático em camundongos infectados com Plasmodium berghei (ANKA)
(Universidade Federal do Pará, 2016-05-10) KAUFFMANN, Nayara; OLIVEIRA, Karen Renata Herculano Matos; http://lattes.cnpq.br/3032008039259369
Malaria is a disease caused by protozoa of the genus Plasmodium and presents itself as a major public health problems in the world. To evaluate the malaria frame, murine models have been used for its similarities between species infective for mice and species infective to man. The increased production of reactive oxygen species and changes in the activity of enzymes such as glutathione peroxidase and superoxide dismutase have been characterized within the clinical picture of the disease, but little is known about the participation of antioxidant molecules such as glutathione in the evolution of the disease. Given the above, the main objective of this study is to evaluate the effect of glutathione in the evolution of murine malaria frame and front to damage caused by infection with Plasmodium berghei ANKA strain (PbA). To this were Balb-C mice, which were inoculated (~106 parasitized erythrocytes) intraperitoneally. The groups were divided into malaria group (PbA), PbA group + GSH 1 mg, PbA group + GSH 3 mg and PbA group + GSH 8 mg treated for 7 days consecutive. The development of the disease was monitored daily by determining the survival, body mass and parasitaemia was monitored every three days in blood strains, was also analyzed the histological sections of liver tissue was performed and the biochemical analysis of liver transaminases. Our data demonstrated that treatment with GSH (8mg/kg) accelerated mortality of infected animals once between days 13-14 after infection about 43% of the animals progressed to death. In the group infected with PbA that received no treatment with GSH, a similar reduction (40%) was observed only from 23-25 days post infection. In relation to PbA + GSH 1mg groups and GSH + PbA 3 mg, there was no difference when compared to the PbA group. Interestingly, although treatment with GSH 8mg has accelerated mortality in the infected group, no significant difference in parasitaemia level of the four groups analyzed. In relation to body mass was observed a difference between day 0 and 24 in all groups, but when analyzed between groups. In what concerns the histological and biochemical tests, we noted that listen both changes in histology and in transaminase, with the latter being expressed in PbA changes group was treated with glutathione 8mg / kg group than in PbA. Concluding that glutathione when administered intraperitoneally accelerates the mortality of mice infected with the ANKA strain, but this mortality is not associated with increased parasitemia, then indicating that mortality may result from liver changes.