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

Abilio Torres Dos Santos Neto,Geanlucas Mendes Monteiro,Maria Lucia Ivo,Rondon Tosta Ramalho,Iandara Schettert Silva,Eduardo Benedetti Parisotto,Camila Tozaki Rodrigues

doi:10.1590/s0102-865020200030000001

Abilio Torres Dos Santos Neto, Geanlucas Mendes Monteiro + Show 5 more

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https://doi.org/10.1590/s0102-865020200030000001

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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.

Highlights

Sickle cell disease (SCD) is a term associated with the group of hemoglobinopathies, characterized by the mutation of chromosome 11 that causes the change of a nitrogen base pair in the sixth position of the beta globin chain; this change causes a replacement of glutamic acid with a valine, producing hemoglobin S (HbS)[1]
Following the reduction of NO, the administration of HU has shown to be able to modulate the physiology of red blood cells and, of nitric oxide synthase, causing its higher bioavailability[17]
After the use of L-NAME, liver tissue showed an increase in the number of Kupffer cells as oxidative stress and inflammatory response rose

Summary

Introduction

Hemoglobin S may occur in the homozygous SS form, called sickle cell anemia, or in association with other structural variants SC, SD as well as in association with β, Sβ + thalassemia, Sβ0 thalassemia. The punctual mutation that occurs with this process leads to frequent hemoglobin polymerization, causing cellular deformation, so that the red blood cell acquires an elongated shape of “sickle”. By adopting this format, several events occur in blood cells, such as vasoocclusion, chronic hemolysis and consequent episodes of pain. The mechanisms of vaso-occlusion are not yet fully understood[3]

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