Oxidative stress, superoxide production, and apoptosis of neutrophils in dogs with chronic kidney disease

Autor: Silva, Adriana Carolina Rodrigues Almeida, Almeida, Breno Fernando Martins, Soeiro, Carolina Soares, Ferreira, Wagner Luis, Lima, Valéria Marçal Felix, Paulo César Ciarlini
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Zdroj: Universidade Estadual Paulista "Júlio de Mesquita Filho"
Popis: Oxidative stress is a key component in the immunosuppression of chronic kidney disease (CKD), and neutrophil function may be impaired by oxidative stress. To test the hypothesis that in uremic dogs with CKD, oxidative stress is increased and neutrophils become less viable and functional, 18 adult dogs with CKD were compared with 15 healthy adult dogs. Blood count and urinalysis were done, and the serum biochemical profile and plasma lipid peroxidation (measurement of thiobarbituric acid reactive substances) were determined with the use of commercial reagents. Plasma total antioxidant capacity (TAC) was measured with a spectrophotometer and commercial reagents, superoxide production with a hydroethidine probe, and the viability and apoptosis of neutrophils with capillary flow cytometry and the annexin V-PE system. The plasma concentrations of cholesterol (P = 0.0415), creatinine (P0.0001), and urea (P0.0001) were significantly greater in the uremic dogs than in the control dogs. The hematocrit (P = 0.0004), urine specific gravity (P = 0.015), and plasma lipid peroxidation (P0.0001) were significantly lower in the dogs that were in late stages of CKD than in the control group. Compared with those isolated from the control group, neutrophils isolated from the CKD group showed a higher rate of spontaneous (0.10 ± 0.05 versus 0.49 ± 0.09; P = 0.0033; median ± standard error of mean) and camptothecin-induced (18.53 ± 4.06 versus 44.67 ± 4.85; P = 0.0066) apoptosis and lower levels of superoxide production in the presence (1278.8 ± 372.8 versus 75.65 ± 86.6; P = 0.0022) and absence (135.29 ± 51.74 versus 41.29 ± 8.38; P = 0.0138) of phorbol-12-myristate-13-acetate stimulation. Thus, oxidative stress and acceleration of apoptosis occurs in dogs with CKD, the apoptosis diminishing the number of viable neutrophils and neutrophil superoxide production.Le stress oxydatif est un élément clé dans l’immunosuppression de maladie rénale chronique (MRC), et la fonction des neutrophiles peut être affectée par le stress oxydatif. Afin de vérifier l’hypothèse que chez les chiens urémiques avec MRC le stress oxydatif est augmenté et les neutrophiles deviennent moins viables et fonctionnels, 18 chiens adultes avec MRC ont été comparés à 15 chiens adultes en santé. Des analyses sanguines et urinaires ont été effectuées, de même que le profil biochimique sérique et la peroxydation des lipides plasmatiques (mesures des substances réactives à l’acide thiobarbiturique) ont été déterminés au moyen de réactifs commerciaux. La capacité antioxydante plasmatique totale (CAT) a été mesurée à l’aide d’un spectrophotomètre et de réactifs commerciaux, la production de superoxyde avec une sonde hydroéthidine, et la viabilité et l’apoptose des neutrophiles avec un cytomètre à flux capillaire et le système d’annexine V-PE. Les concentrations plasmatiques de cholestérol (
Databáze: OpenAIRE