RESUMO
Resistance physical exercise has neuroprotective and anti-inflammatory effects on many known diseases and, therefore, it has been increasingly explored. The way in which this type of exercise exerts these actions is still under investigation. In this study, we aimed to analyze the enzymes and components of the purinergic system involved in the inflammatory process triggered by the P2X7R. Rats were divided into four groups: control, exercise (EX), lipopolysaccharide (LPS), and EX + LPS. The animals in the exercise groups were subjected to a 12-week ladder-climbing resistance physical exercise and received LPS after the last session for sepsis induction. Enzymes activities (NTPDase, 5'-nucleotidase, and adenosine deaminase), purinoceptors' density (P2X7R, A1, and A2A), and the levels of inflammatory indicators (pyrin domain-containing protein 3 (NLRP3), Caspase-1, interleukin (IL)- 6, IL-1B, and tumor necrosis factor (TNF) -α) were measured in the cortex and hippocampus of the animals. The results show that exercise prevented (in the both structures) the increase of: 1) nucleoside-triphosphatase (NTPDase) and 5'-nucleotidase activities; 2) P2X7R density; 3) NLRP3 and Caspase-1; and 4) IL-6, IL-1ß, and TNF-α It is suggested that the purinergic system and the inflammatory pathway of P2X7R are of fundamental importance and influence the effects of resistance physical exercise on LPS-induced inflammation. Thus, the modulation of the P2X7R by resistance physical exercise offers new avenues for the management of inflammatory-related illnesses.
Assuntos
Lipopolissacarídeos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Ratos , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Lipopolissacarídeos/toxicidade , 5'-Nucleotidase/metabolismo , Doenças Neuroinflamatórias , Hipocampo/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Exercício Físico , Caspases/metabolismo , Receptores Purinérgicos P2X7/metabolismoRESUMO
Chagas disease (CD) is caused by the parasite Trypanosoma cruzi. CD affects people worldwide, primarily in tropical areas. The central nervous system (CNS) is an essential site for T. cruzi persistence during infection. The protozoan may pass through the blood-brain barrier and may cause motor and cognitive neuronal damage. Once in the CNS, T. cruzi triggers immune responses that the purinergic system can regulate. Treatment for CD is based on benznidazole (BNZ); however, this agent has negative side-effects and is toxic to the host. For this reason, we investigated whether resveratrol (RSV), a potent antioxidant and neuroprotective molecule, would modulate purinergic signaling and RSV alone or in combination with BNZ would prevent changes in purinergic signaling and oxidative damage caused by T. cruzi. We infected mice with T. cruzi and treated them with RSV or BNZ for 8 days. Increases in ATP and ADP hydrolysis by NTPDase in the total cortex of infected animals were observed. The treatment with RSV in infected group diminished ATP, ADP, and AMP hydrolysis compared to infected group. The combination of RSV + BNZ decreased AMP hydrolysis in infected animals compared to the INF group, exerting an anti-inflammatory effect. RSV acted as a neuroprotector, decreasing adenosine levels. Infected animals presented an increase of P2X7 and A2A density of purine receptors. RSV reduced P2X7 and A2A and increased A1 density receptors in infected animals. In addition, infected animals showed higher TBARS and reactive oxygen species (ROS) levels than control. RSV diminished ROS levels in infected mice, possibly due to antioxidant properties. In short, we conclude that resveratrol could act as a neuroprotective molecule, probably preventing inflammatory changes caused by infection by T. cruzi, even though the mice experienced high levels of parasitemia.
Assuntos
Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Doença de Chagas/metabolismo , Nitroimidazóis/administração & dosagem , Receptores Purinérgicos/biossíntese , Resveratrol/administração & dosagem , Doença Aguda , Animais , Antioxidantes/administração & dosagem , Córtex Cerebral/parasitologia , Doença de Chagas/tratamento farmacológico , Feminino , Expressão Gênica , Imunossupressores/administração & dosagem , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Receptores Purinérgicos/genéticaRESUMO
Sepsis is a generalized infection that involves alterations in inflammatory parameters, oxidant status, and purinergic signaling in many tissues. Physical exercise has emerged as a tool to prevent this disease because of its anti-inflammatory and antioxidant properties. Thus, in this study, we investigated the effects of physical exercise on preventing alterations in purinergic system components, oxidative stress, and inflammatory parameters in lipopolysaccharide (LPS)-induced sepsis in rats. Male Wistar rats were divided into four groups: control, exercise (EX), LPS, and EX+LPS. The resisted physical exercise was performed for 12 weeks on a ladder with 1 m height. After 72 hours of the last exercise session, the animals received 2.5 mg/kg of LPS for induction of sepsis, and after 24 hours, lungs and blood samples were collected for analysis. The results showed that the exercise protocol used was able to prevent, in septic animals: (1) the increase in body temperature; (2) the increase of lipid peroxidation and reactive species levels in the lung, (3) the increase in adenosine triphosphate levels in serum; (4) the change in the activity of the enzymes ectonucleotidases in lymphocytes, partially; (5) the change in the density of purinergic enzymes and receptors in the lung, and (6) the increase of IL-6 and IL-1ß gene expression. Our results revealed the involvement of purinergic signaling and oxidative damage in the mechanisms by which exercise prevents sepsis aggravations. Therefore, the regular practice of physical exercise is encouraged as a better way to prepare the body against sepsis complications.