**1. Introduction**

30 Blood Cell – An Overview of Studies in Hematology

*12* (68), 6511-6518.

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Red blood cells are responsible for oxygen transport from lung to tissues. Oxygen transport depends on reduced state of iron (Fe2+) in hemoglobin. To accomplish their delivery function erythrocytes must accommodate to the environment conditions as they change along the vascular branches. Both element oxygen (O2) and iron are able to quickly shift their oxidative state in response to different external/internal emerging stimuli. Moreover in erythrocyte nitric oxide (NO●) a vasodilalatory messenger is present. All these elements act in normal condition in well established mechanisms but they may generate alone or together high reactive species, named free radicals, that damage red blood cells as well as vascular endothelium. Free radicals may be generated from both oxygen and nitrogen and are known as reactive oxygen species (ROS) respectively nitrogen reactive species (RNS). However erythrocytes have intracellular enzyme/non enzyme defense system. When reactive species are quickly and intensely generated under external/internal stimuli the activity of antioxidant defense system is overwhelmed. Free radicals generation is triggered by normal, adaptive or pathological stimuli such as: superoxide detoxification, decreasing oxygen saturation in vascular branches, shear stress or atherosclerosis, ischemic attack and bacterial infections.

One of the most potent oxidant agents in living cells is homocysteine (Hcy) a metabolic compound from methionine metabolism. The already mention metabolism requires vitamin B12, B6 and folic acid involvement. Every deficiency in vitamins supplies or enzymes activity triggers the onset of different diseases and erythrocyte is first affected in megaloblastic or Biermer anemia. A secondary consequence of vitamins deficiency is hyperhomocysteinemia. HyperHcy represents a high risk in cardiovascular diseases and not only. Nowadays is generally accepted that Hcy disturbs the normal endothelial function, promoting thrombosis and inhibiting fibrinolysis through many mechanisms which can possibly integrate and are

© 2012 Cristiana et al., licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2012 Cristiana et al., licensee InTech. This is a paper distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2012 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

not mutually exclusive; oxidative processes, decreasing NO bioavailability and specific protein targeting.

Homocysteine in Red Blood Cells Metabolism – Pharmacological Approaches 33

Transitional metals (Fe belongs to this group) particularly behave. They have a single unpaired electrons in theirs outer orbitals, but they don't behave as free radicals because within cells they are attached to proteins in most cases. However they are able to catalyze

Reactive species of oxygen refers to a group of highly reactive O2 metabolites, including superoxide anion (O2•-), hydrogen peroxide (H2O2), singlet oxygen (1O2), and hydroxyl radical (OH•), that can be formed within cells. Reactive oxygen species are constantly formed as byproducts in normal enzymatic reaction in all human cells through normal aerobic processes as mitochondrial oxidative phosphorylation or as necessary products in neutrophils in order to kill invading pathogens. The above mentioned phenomena are

Erythrocytes must save oxygen for delivering it to the cells; as a consequence red blood cells lack mitochondrion the main oxygen consumer within cell. In this particular condition the

In order to understand oxygen behavior an inside in its structure is needed. The ground state of oxygen is triplet oxygen meaning that the molecule has two unpaired electrons

These electrons can't travel both in the same orbital because they have parallel spin (they spin in the same direction). As a consequence molecular oxygen is paramagnetic and from this feature it was concluded that the structure in the right may be assigned to O2 (figure1). Although O2 is very reactive from thermodynamic standpoint its single electrons cannot react rapidly with already paired electrons in the covalent bond of organic molecules (abundant in living cells). As a consequence it is harmless to these molecules. Instead molecular oxygen can rapidly react with single unpaired electrons from transitory metals (e.g. Fe, Cu, Mn). One mole of properly chelated cooper could catalyze consumption of all of

In fact oxygen O2 is both kinetically stable thus not reactive and very reactive promoting

Within cells where transitional metals are bounded to proteins (in metal containing proteins or enzymes) oxidative attack of O2 tend to be slow, meaning that a first single electron is

) will form very slow.

electron transfer in many processes and sometimes generate radicals.

source of ROS in erythrocyte may be the carried oxygen itself.

*2.1.2. Reactive oxygen species* 

consuming oxygen processes.

occupying two different molecular orbitals.

**Figure 1.** The structure of oxygen molecule

the oxygen in an average room within one second in [2].

fast reactions, depending the surrounding conditions.

relatively difficult to add. As a consequence superoxid radical (O2

The already specified free radicals are not all "bad". NO● can be regarded as a "good radical" but it is inactivated by many Hcy-dependent Mechanisms that finally impair its vasodilatatory function. Thus damaging Hcy effects expands to the environment where erythrocytes move and act. As a consequence directly and indirectly Hcy has a big impact on erythrocytes whose deformability in shear stress is crucial for circulatory function. Taken into account all these factors pharmacological approaches envisage lowering homocysteine levels by different ways such as: vitamins B supplementation, antioxidant drugs, hypotensive agent, antithrombotic drugs etc. Some of these patterns such is vitamins supplementation proved to have limited clinical benefits while others as nitrite/nitrate are still in debates. Because most pathological processes mentioned above involve oxidative pathway mechanism, pharmacological presentation will focus on drugs with antioxidant properties

As a conclusion the effect of elevated homocysteine appears multifactorial affecting both the vascular wall structure, function as well as erythrocytes metabolism.
