RESUMEN
Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. The crosstalk occurs between the primary focus of infection and lung and other organ systems including the central nervous system via soluble and cellular inflammatory mediators and that this involves both the innate and adaptive immune systems. These interactions are reflected by genomic changes and abnormal rates of cellular apoptosis. The lungs and the brain are rapidly affected due to an inflammatory response and oxidative stress in sepsis. Physical exercise promotes positive responses in the inflammatory cascade and oxidative/antioxidant system. In this sense, we aimed at determining the possible protectant effects of a physical exercise program against inflammation and oxidative stress on the lungs and the brain of rats subjected to sepsis. Adult male Wistar rats were randomly assigned to the sham + sedentary (S), sham + trained (T), and cecal ligation and perforation (CLP) + S and CLP + T and subjected to a physical exercise program using a treadmill for 21 days. Forty-eight hours after the last training session, sepsis was induced by the CLP model. Twenty-four hours later, the animals were euthanized and the lungs, the hippocampus, and the prefrontal cortex were harvested to determine the levels of cytokines by enzyme-linked immunosorbent assay (ELISA) and nitrite and reactive oxygen species production, oxidative damage to proteins, and antioxidant enzymes by spectrophotometric method. Sepsis increased the lung and brain levels of TNF-α, IL-1ß, and IL-6, while diminished IL-10 levels, elevated nitrite levels and reactive oxygen species production, augmented the levels of protein carbonyls and diminished the sulfhydryl content, and decreased SOD activity and GSH levels. The exercise program diminished the levels of TNF-α, IL-1ß, IL-6, nitrite, and reactive oxygen species production, as well as the levels of protein carbonyls but augmented the sulfhydryl content, and elevated SOD activity. In conclusion, the exercise program protected the lungs and the brain of septic rats against inflammation and oxidative stress.
Asunto(s)
Antioxidantes , Estrés Oxidativo , Condicionamiento Físico Animal , Sepsis , Animales , Antioxidantes/metabolismo , Encéfalo/metabolismo , Modelos Animales de Enfermedad , Inflamación/metabolismo , Inflamación/prevención & control , Interleucina-6/metabolismo , Pulmón/metabolismo , Masculino , Nitritos , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno , Sepsis/complicaciones , Sepsis/metabolismo , Superóxido Dismutasa/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BACKGROUND: The choroid plexus (CP), main component of blood-cerebrospinal fluid barrier (BCSFB), protects the brain from peripheral inflammation similar to the blood-brain barrier. Thus, CP is considered a critical target site of oxidative damage, which in sepsis oxidative stress is likely to be a major step in the development of brain damage. Functional alterations in CP may be associated with sepsis-induced brain injury. However, there is no description on the mechanisms associated with BCSFB disruption during sepsis development. MATERIALS AND METHODS: To test this hypothesis, we examined time-dependent oxidative stress markers in CP and permeability of BCSFB in rats submitted to polymicrobial sepsis by cecal ligation and puncture (CLP) or sham surgery (control). We assessed albumin cerebrospinal fluid/plasma concentration quotient (Qalb), an index of BCSFB dysfunction and in CP samples, the oxidative damage in lipids, proteins, antioxidant enzymes and nitrite/nitrate (N/N) concentration in 12, 24 and 48â¯h after CLP. RESULTS: The increase of BCSFB permeability is time-related to the increase of N/N concentration, oxidative damage to lipid and proteins, and decrease of antioxidant enzyme superoxide dismutase activity at 12â¯h in the CP; and decrease of catalase activity in 12 and 24â¯h. CONCLUSIONS: In experimental sepsis the BCSFB dysfunction occurs and oxidative stress seems to be a major step in this dysfunction.