Effects of oxidative stress on liver, brain and spinal cord of rats using L-NAME and treated with hydroxyurea. A model of sickle cell complication

Abstract Purpose: To analyze the serum levels of nitric oxide and correlate them with the levels of thiobarbituric acid reactive substances (TBARS) in liver, brain and spinal cord of animals using L-NAME and treated with hydroxyurea. Methods: Eighteen male albino Wistar rats were divided into three groups. NG-nitro-L-arginine methyl ester (L-NAME) was intraperitoneally administered to induce oxidative stress. TBARS and plasma nitric oxide levels were analyzed in all groups. Histopathology of the liver and vascular tissue was performed. Results: Statistically significant differences were seen in liver, brain and spinal cord TBARS levels. Conclusions: Following the use of L-NAME, hepatic tissue increased the number of Kupffer cells as oxidative stress and inflammatory response increased. The use of L-NAME caused an increase in lipid peroxidation products and, consequently, in oxidative stress in animals. Hydroxyurea doses of 35 mg / kg / day reduced TBARS values in liver, brain and spinal cord.

Pathophysiological insights in sickle cell disease.

The first coherent pathophysiological scheme for sickle cell disease (SCD) emerged in the sixties-seventies based on an extremely detailed description of the molecular mechanism by which HbS in its deoxy-form polymerises and forms long fibres within the red blood cell that deform it and make it fragile. This scheme explains the haemolytic anaemia, and the mechanistic aspects of the vaso-occlusive crises (VOCs), but, even though it constitutes the basic mechanism of the disease, it does not account for the processes that actually trigger VOCs. This paper reviews recent data which imply: red blood cell dehydration, its abnormal adhesion properties to the endothelium, the participation of inflammatory phenomenon and of a global activation of all the cells present in the vessel, and finally, abnormalities of the vascular tone and of nitric oxide metabolism. These data altogether have shed a new light on the pathophysiology of the first molecular disease i.e. sickle cell disease.

Radicais livres em eritrócitos falcêmicos e talassêmicos / Free radicals in erythrocytes in sickle cell anemia and thalassemia

Radicais livres derivados de espécies ativadas de oxigênio estao associados a lesoes citológicas, que diminuem a sobrevida dos eritrócitos, especialmente quando contêm defeitos congênitos, como sao os casos da anemia falciforme e da talassemia maior. As atividades antioxidantes dos eritrócitos dependem de três tipos de enzimas: superóxido dismutase, catalase e glutatiao peroxidase. Entretanto, as atividades antioxidantes podem ser ineficazes em situaçoes em que ocorrem o comprometimento dos hidroxiperóxidos da membrana eritrocitária, devido às células falciformes irreversíveis e à ligaçao de hemicromos à membrana dos eritrócitos talassêmicos.