Carnosine protects erythrocytes from the oxidative stress caused by homocysteic acid (original) (raw)

Doklady Biochemistry and Biophysics, 2008

Abstract

In this work, we demonstrate that homocysteic acid provokes oxidative stress in erythrocytes and decreases their hemolytic resistance, whereas the natural antioxidant carnosine [9] protects erythrocytes from its toxic effect. The discovered property can be used for development of new methods for protecting erythrocytes in hyperhomocysteinemia. Homocysteine and homocysteic acid (HCA), the product of spontaneous homocysteine oxidation, are important risk factors for neurodegenerative and cardiovascular diseases [1]. These compounds induce oxidative stress in brain neurons [2, 3] and lymphocytes [4], resulting from their toxic effect on the nervous and immune systems. The prooxidant effect of homocysteine and homocysteic acid on cell structures can be realized via both the glutamate receptors [3, 4] and the activation of NO synthase or inhibition of Na/KATPase, as was demonstrated for the vascular endothelium [5, 6]. It is known that erythrocytes are capable of accumulating homocysteine and excreting it into the extracellular medium [7, 8]. Erythrocytes constitute the main part of blood cells; correspondingly, the toxic effect of homocysteine and HCA may cover these cells as well. However, the effect of these compounds on the erythrocyte stability has not been studied. The goal of this work was to analyze the effect of HCA on human erythrocytes and to assess the effect of carnosine on the oxidative stress in erythrocytes caused by HCA. Various factors can cause erythrocyte hemolysis, including a decreased ambient osmotic pressure, decreased pH, and oxidants [10‐12]. The resistance of erythrocytes to hemolytic action is an integral parameter characterizing their integrity and viability as well as a criterion of their physiologically native state. Two models of hemolysis were used in this work, namely, the osmotic hemolysis and the hemolysis caused by hydrochloric acid. The former takes place with a decrease in the tonicity of medium produced by diluting cell suspension with distilled water. In this process, cells swell with subsequent disruption of the cell membrane. The latter is induced by supplementing cell suspension with hydrochloric acid, which leads to a decrease in the pH in the cytoplasm, impairments in the cytoskeleton structure, and, eventually, cell swelling and destruction [13].

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