RESUMO
Hypothermic preservation of the organ for transplantation causes vascular damage; therefore, the preservation of vascular function is important for the organs to function correctly after transplantation. The aim of the present study is to evaluate the influence of prolonged cold storage (72 hours) on vascular responses to 5-hydroxytryptamine (5-HT) and potassium chloride (KCl), each of which causes receptor-dependent and receptor-independent contractions, respectively. We also examined the protective roles of superoxide dismutase (SOD), L-arginine, the precursor of nitric oxide, iloprost, a synthetic analogue of prostaglandin I(2) with vasodilator functions, or endothelium removal for vascular responses. Endothelium-intact rings were prepared from the rat thoracic aorta, and stored at 4 degrees C for up to 72 hours in Krebs solution alone or Krebs solution that contains SOD, L-arginine or iloprost. The vascular responses were investigated daily. The Analysis of Variance (ANOVA) followed by Dunn test was used for statistical analysis. Being kept in cold in Krebs solution diminished the vascular responses to 5-HT and KCl. The presence of SOD in Krebs solution successfully prevented the decline in these responses, while iloprost or L-arginine partially restored them. In the endothelium-denuded rings, the 5-HT-induced contraction remained protected after 72 hours, whereas the KCl-induced contraction was partially restored. These results indicate that cold preservation declines the 5-HT and KCl-induced vascular responses, which can be partially prevented by iloprost or L-arginine, and can be restored by endothelium removal or SOD. Therefore, superoxide anion and endothelium-derived factors contribute to the decline in the contracting function of the aorta during prolonged cold storage.
Assuntos
Aorta Torácica/efeitos dos fármacos , Aorta Torácica/fisiologia , Criopreservação , Contração Muscular/efeitos dos fármacos , Cloreto de Potássio/farmacologia , Serotonina/farmacologia , Acetilcolina/farmacologia , Animais , Técnicas In Vitro , Masculino , Ratos , Ratos Sprague-Dawley , Receptores de Serotonina/metabolismo , Fatores de TempoRESUMO
Ionizing radiation is widely used for the treatment of solid tumors and it is thought to act by directly targeting tumor clonogens, also known as stem cells. Apoptosis is a genetically programmed mechanism of cell death often characterized by internucleosomal DNA cleavage. Although it has been previously shown that lymphocytes readily undergo apoptosis in patients receiving anticancer drugs or treatment with ionizing radiation, this is the first study to investigate the influence of radiotherapy and melatonin on apoptosis in rat lymphocytes at two different times of the day. Melatonin, a free radical scavenger, is an endogenous neurohormone predominantly synthesized in and secreted by the pineal gland. It has been shown that melatonin inhibits apoptosis in normal cells but it increases the rate of apoptosis in various cancer cells. Therefore, in the present study, the effect of melatonin on apoptosis in cultured lymphocytes was studied after total body irradiation (TBI) was given to rats in the morning (1 HALO) or evening (13 HALO) with morphological and DNA fragmentation analysis. Two-way analysis of variance (ANOVA) revealed that radiation increased the rate of apoptosis in rat lymphocytes after TBI, and melatonin treatment did not reduce the rate of apoptosis after TBI at either time point. We conclude that the lack of an effect of melatonin on the apoptosis rate in rat lymphocytes might be due to the dose-dependent effect of melatonin, the time course of apoptosis investigated, or the cell type in which apoptosis was examined.
Assuntos
Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Linfócitos/efeitos dos fármacos , Linfócitos/efeitos da radiação , Melatonina/farmacologia , Animais , Células Cultivadas , Relação Dose-Resposta a Droga , Raios gama , Masculino , Ratos , Ratos Wistar , Fatores de Tempo , Irradiação Corporal TotalRESUMO
Ionising radiation is known one of the most effective tools in the therapy of cancer but in many thoracic cancers, the total prescribed dose of radiation that can be safely administered to the target volume is limited by the risk of complications arising in the normal lung tissue. One of the major reasons for cellular injury after radiation is the formation of reactive oxygen species (ROS). Radiation pneumonitis is an acute phase side-effect which generally subsides after a few weeks and is followed by a chronic phase characterized by inflammation and fibrosis, that can develop months or years after irradiation. Carnosine is a dipeptide composed by the amino acids beta-histidine and l-alanine. The exact biological role of carnosine is not totally understood, but several studies have demonstrated that it possesses strong and specific antioxidant properties, protects against radiation damage,and promotes wound healing. The antioxidant mechanism of carnosine is attributed to its chelating effect against metal ions, superoxide dismutase (SOD)-like activity, ROS and free radicals scavenging ability . Either its antioxidant or anti-inflammatuar properties, we propose that carnosine ameliorates irradiation-induced lung injury. Thus, supplementing cancer patients to whom applied radiation therapy with carnosine, may provide an alleviation of the symptoms due to radiation-induced lung injury. This issue warrants further studies.