Association of cerebral malaria and TNF-alpha levels: a systematic review

This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) – Código de Financiamento 001.Federal University of Pará. Institute of Biological Sciences. Laboratory of Functional and Structural Biology. Belém, PA, Brazil.Federal University of Pará. Institute of Health Sciences. Postgraduate Program in Pharmaceutical Sciences. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Functional and Structural Biology. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Functional and Structural Biology. Belém, PA, Brazil.University of Alberta. Faculty of Medicine and Dentistry. School of Dentistry. Edmonton, Canada.Federal University of Rio de Janeiro. School of Dentistry. Department of Pediatric Dentistry and Orthodontics. Rio de Janeiro, RJ, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Functional and Structural Biology. Belém, PA, Brazil.Background: Cerebral malaria is the most severe form of infection with Plasmodium falciparum characterized by a highly inflammatory response. This systematic review aimed to investigate the association between TNF-α levels and cerebral malaria. Methods: This review followed the Preferred Reporting of Systematic Review and Meta-analyses (PRISMA) guidelines. The search was performed at PubMed, LILACS, Scopus, Web of Science, The Cochrane Library, OpenGrey and Google Scholar. We have included studies of P. falciparum-infected humans with or without cerebral malaria and TNF-α dosage level. All studies were evaluated using a risk of bias tool and the GRADE approach. Results: Our results have identified 2338 studies, and 8 articles were eligible according to this systematic review inclusion criteria. Among the eight articles, five have evaluated TNF- α plasma dosage, while two have evaluated at the blood and one at the brain (post-Morten). Among them, only five studies showed higher TNF-α levels in the cerebral malaria group compared to the severe malaria group. Methodological problems were identified regarding sample size, randomization and blindness, but no risk of bias was detected. Conclusion: Although the results suggested that that TNF-α level is associated with cerebral malaria, the evidence is inconsistent and imprecise. More observational studies evaluating the average TNF-alpha are needed

Chronic methylmercury exposure causes spinal cord impairment: proteomic modulation and oxidative stress

Conselho Nacional de Desenvolvimento Científico e Tecnológico – Brasil (CNPq) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Brasil (CAPES) - Finance Code 001; Universidade Federal do Pará (PROPESP, UFPA, Brazil)Federal University of Pará. Institute of Biological Sciences. Laboratory of Functional and Structural Biology. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Functional and Structural Biology. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Functional and Structural Biology. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Functional and Structural Biology. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Functional and Structural Biology. Belém, PA, Brazil.University of São Paulo. Department of Biological Sciences. Bauru Dental School. Bauru, SP, Brazil.University of São Paulo. Department of Biological Sciences. Bauru Dental School. Bauru, SP, Brazil.Federal University of Pará. Laboratory of Molecular Pharmacology. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Functional and Structural Biology. Belém, PA, Brazil.Methylmercury (MeHg) is considered by the World Health Organization (WHO) as one of the chemicals of greatest public health concern. Although central nervous system (CNS) is the main target organ, the effects over the spinal cord are not well understood, especially in chronic exposure at similar doses to those faced by humans. This study aimed to investigate possible changes on global proteomic profile and oxidative biochemistry status of rats spinal cord, related to the maintenance and balance of the organism functioning, mimicking a human daily exposure by diet (chronic and with relatively low levels). For this, 28 adults male Wistar rats were divided into two groups: MeHg group, which was intoxicated by intragastric gavage with MeHg at a dose of 0.04 mg/kg/day for 60 days, and control group, that received only vehicle. After the exposure period, the spinal cords were collected for evaluation of total mercury levels, proteomic profile, with further bioinformatic overrepresentation analysis (ORA), and oxidative biochemistry, by analyzing the antioxidant capacity against peroxyl radicals (ACAP), lipid peroxidation (LPO), nitrite levels, measurement of Trolox Equivalent Antioxidant Capacity (TEAC) and Reduced Glutathione (GSH). The MeHg exposure increased total mercury levels in spinal cord parenchyma, which increased lipid peroxidation and nitrite levels, and reduced antioxidant status. The proteomic analysis showed several proteins related to biological processes, cellular components and molecular functions. Moreover, according to the ORA analysis, the proteins are involved in processes such as mitochondrial activity, stress response, cytoskeleton and apoptosis. Therefore, we concluded that exposure to low doses of MeHg can activate the oxidative stress pathway and thus, modulate the status of regulation of several important proteins