ABSTRACT
BACKGROUND: Ischemia-reperfusion injury (IRI) remains a major problem in renal transplantation, and the inflammatory response to IRI exacerbates the resultant renal injury. We have investigated whether the systemic administration of cardiotrophin-1 (CT-1) is able to improve renal function and to decrease inflammatory responses in a rat model of renal IRI. METHODS: IRI was induced by renal pedicle clamping (60 min) followed by reperfusion and contralateral nephrectomy. CT-1 was injected through the penile vein 30 min before clamping release and its effects were compared with a saline-treated group at five different time points of reperfusion. RESULTS: Survival in the CT-1-treated group was higher than in the untreated group and prevented IRI-induced reduction in the glomerular filtration rate, as shown by blunted increases in creatinine and urea plasma levels and less severe decrease in creatinine clearance. These effects of CT-1 seem to be mediated by reduction in oxygen-radical production, increased superoxide dismutase expression, attenuation of neutrophil and macrophage infiltration, lower adhesion molecule expression, lower inflammation demonstrated by a decrease of plasma levels of proinflammatory cytokine secretion such as tumor necrosis factor-α, interleukin-1ß and interferon-γ, lower inducible nitric oxide synthase expression and lower nuclear factor-κB activation, and reduced apoptosis. CONCLUSIONS: Therefore, these results suggest that CT-1 administration prevents IRI and it might be used as a therapeutic strategy to protect the kidney against IRI.
Subject(s)
Cytokines/administration & dosage , Kidney Transplantation/methods , Kidney/pathology , Reperfusion Injury/pathology , Animals , Apoptosis , Inflammation , Interferon-gamma/metabolism , Interleukin-1beta/metabolism , Macrophages/metabolism , Male , NF-kappa B/metabolism , Neutrophils/metabolism , Nitric Oxide Synthase Type II/metabolism , Peroxidase/metabolism , Rats , Rats, Wistar , Reactive Oxygen Species , Reperfusion Injury/prevention & control , Superoxide Dismutase/metabolism , Superoxides/metabolism , Time Factors , Tumor Necrosis Factor-alpha/metabolismABSTRACT
UNLABELLED: Bisphenol-A (BPA) is used to manufacture dental materials such as sealants, fillings and cements. There is evidence of its estrogenic effects on recipients after the placement of dental sealants. Pituitary and especially prolactin (PRL) cells are targets for estrogens. OBJECTIVES: The aim of this research was to determine if BPA eluted from dental resins can alter the proliferation of pituitary cells and PRL cells in the short, medium and long term in a case-control assay. METHODS: Two dental fillings were inserted in the lower incisors of Wistar rats divided into groups sacrificed after one, three, five and seven months. Immunocytochemical treatment was carried out in order to determine proliferating cell nuclear antigen (PCNA) positive cells, PRL-positive cells, PRL- and PCNA-positive cells. RESULTS: A significant increase of PCNA-positive cells after one (p < 0.05), three (p < 0.01) and five months (p < 0.01) was recorded. PRL-positive cells showed no statistically significant difference between intervened animals and controls. PRL- and PCNA-positive cells manifested a significant increase after five months (p < 0.05). A significant decrease in proliferating cells was observed after seven months (p < 0.05) for PCNA-positive cells and (p < 0.01) for PRL- and PCNA-positive cells. CONCLUSION: Low quantities of BPA eluted during mastication can affect immunocytochemical patterns of pituitary cells, increasing cellular proliferation in the short, medium and long term although PRL cell population remained unaffected after dental fillings.
