RESUMO
Aging and reduced longevity are due in part to the action of free radicals (FR). Melatonin (Mel) and thioctic acid (TA) are effective in protecting against the damage caused by FR. In this study, the effect of Mel and TA on the life cycle of Drosophila melanogaster was determined. We used a control group of flies, another group that was provided with Mel (0.43 mM) throughout their life cycle (Mel-c), a third group received Mel upon reaching adulthood (Mel-a) and two groups were fed with TA (2.15 mM) in the same manner (TA-c and TA-a). The number of eclosed, survival, phenotype changes, motor activity and the content of malondialdehyde (MDA) was evaluated in each group. Mel-c increased the eclosion rate and the motor activity of the flies. Mel-c and Mel-a increased the life span and decreased the concentrations of MDA. By contrast, TA-c diminished the eclosion rate, produced phenotypic changes and increased MDA levels and motor activity of the flies. TA-a extended the life span of flies, and did not alter MDA levels and motor activity when compared with the control group. In conclusion, Mel mitigated the effects caused by FR generated during aging, while TA-c increased lipid peroxidation and altered the phenotype of flies.
Assuntos
Antioxidantes/farmacologia , Drosophila melanogaster/efeitos dos fármacos , Longevidade/efeitos dos fármacos , Melatonina/farmacologia , Ácido Tióctico/farmacologia , Animais , Feminino , Humanos , MasculinoRESUMO
Renal inflammation and oxidative stress are constantly present in experimental hypertension. Since the spontaneously hypertensive rat (SHR) has reduced levels of hepatocyte growth factor (HGF), which suppresses the activation of the proinflammatory nuclear transcription factor kappa B (NF-κB), we speculated that HGF deficiency could play a key role in the pathogenesis of hypertension in the SHR. To test this hypothesis we increased HGF in the SHR by HGF gene delivery. We found that kidneys of 15-week-old SHR had an important reduction in HGF mRNA and protein expression. Adult SHRs were randomly assigned to receive weekly hydrodynamic injection (1mg/kg) of a naked plasmid containing human HGF (hHGF) gene associated with a cytomegalovirus promoter (pCMV-HGF) or empty vector (pcDNA3.1) during 6weeks. WKY rats treated with pcDNA3.1 and pCMV-HGF served as controls. The kidneys in the hypertensive SHR untreated and treated with the empty vector had increased NF-κB activation, elevated mRNA and protein expression of RANTES, MCP-1 and IL-6 and increased oxidative stress. Activity of Na(+)-ATPase was increased while activity of Na(+), K(+)-ATPase was normal. hHGF gene therapy normalized renal NF-κB activity, proinflammatory cytokines, antioxidant status (GSH, SOD and CAT), Na(+)-ATPase activity, reduced renal injury and ameliorated hypertension. Our results suggest that reduction in HGF production plays a major role in the pathogenesis of hypertension in the SHR and increasing HGF is a potential therapeutic target in the treatment of hypertension.
Assuntos
Adenosina Trifosfatases/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Fator de Crescimento de Hepatócito/biossíntese , Hipertensão/genética , Mediadores da Inflamação/metabolismo , Animais , Antioxidantes/metabolismo , Peso Corporal , Quimiocina CCL2/metabolismo , Quimiocina CCL5/metabolismo , Técnicas de Transferência de Genes , Terapia Genética/métodos , Fator de Crescimento de Hepatócito/genética , Fator de Crescimento de Hepatócito/metabolismo , Humanos , Hipertensão/enzimologia , Hipertensão/metabolismo , Inflamação/genética , Inflamação/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Nefropatias/genética , Nefropatias/metabolismo , Masculino , NF-kappa B/metabolismo , Estresse Oxidativo/genética , RNA Mensageiro/genética , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , ATPase Trocadora de Sódio-Potássio/metabolismo , TransgenesRESUMO
Autonomic and peripheral neuropathies are well-described complications in diabetes. Diabetes mellitus is also associated to central nervous system damage. This little-known complication is characterized by impairment of brain functions and electrophysiological changes associated with neurochemical and structural abnormalities. The purpose of this study was to investigate brain structural and ultrastructural changes in rats with streptozotocin-induced diabetes. Cerebral cortex, hypothalamus, and cerebellum were obtained from controls and 8 weeks diabetic rats. Light and electron microscope studies showed degenerative changes of neurons and glia, perivascular and mitochondrial swelling, disarrangement of myelin sheath, increased area of myelinated axons, presynaptic vesicle dispersion in swollen axonal boutoms, fragmentation of neurofilaments, and oligodendrocyte abnormalities. In addition, depressive mood was observed in diabetic animals. The brain morphological alterations observed in diabetic animals could be related to brain pathologic process leading to abnormal function, cellular death, and depressive behavioral.
Assuntos
Cerebelo/ultraestrutura , Córtex Cerebral/ultraestrutura , Diabetes Mellitus Experimental/patologia , Hipotálamo/ultraestrutura , Animais , Apoptose , Axônios/patologia , Depressão , Marcação In Situ das Extremidades Cortadas , Masculino , Microscopia Eletrônica de Transmissão , Mitocôndrias/ultraestrutura , Dilatação Mitocondrial , Bainha de Mielina/ultraestrutura , Oligodendroglia/ultraestrutura , Ratos , Ratos Sprague-Dawley , Sinapses/ultraestruturaRESUMO
Depression is frequently observed among patients with diabetes and depressive status has been associated to activation of inflammatory processes, suggesting a role of depression in the inflammatory events observed in diabetes. To test that proposal, it was studied the effect of depression induced by forced swimming test (FST) on the evolution of early diabetic nephropathy. Diabetes was induced by streptozotocin injection. Rats were submitted to FST for 15 days. Struggle time was determined during FST and motor activity previously to FST. Nitric oxide, malondialdehyde, reduced glutathione and catalase activity were measured in kidney homogenates by enzymatic and biochemical methods. Superoxide anion, monocyte/macrophage (ED-1 positive cells) and RAGE were determined by histochemical and immunohistochemical methods. Diabetic rats had decreased struggle time and locomotor activity at day 1 of FST. Both control and diabetic rats had those parameters decreased at day 15. Renal oxidative stress, RAGE expression and ED-1 cells were observed increased in diabetic animals. Those parameters were not significantly altered by FST. The depressive status does not alter oxidative and immune parameters during the early renal changes of diabetic nephropathy.