**4. Reactive oxygen species and oxidative stress**

In physiological conditions a delicate balance exists between ROS production and the antioxidant capacity. A higher ROS production and/or a decreased antioxidant capacity is responsible for the harmful effects of free radicals or the oxidative stress (OS). Oxidative stress represents an important pathogenic mechanism involved in inflammation, cancerogenesis or aging [24].

End products of free radicals action, aldehydes, inhibit the activity of membrane enzymes (glucose-6-phosphate, adenylate cyclase). These aldehydes react selectively with proteins or enzymes containing SH groups and cause tissue destructions.

The emergence of OS is one of the most important pathogenic mechanisms involved in inflammation, carcinogenesis, radiation disease and aging.

#### 30 Lipid Metabolism

The objective of various experimental models was to study erythrocyte response to oxidant substances action. Erythrocyte characteristics and test substance dosing allowed the evaluation of OS; these experiments can be extrapolated to explain various physiological or pathological processes in the body.

Oxidative Stress and Lipid Peroxidation – A Lipid Metabolism Dysfunction 31

radicals

produced in quantities which do not exceed the antioxidant capacity. Thus, the superoxide anion is produced by leukocytes during phagocytosis and in smooth muscle cells, epithelial

The anion produced by macrophages and endothelial cells induces conformational changes of receptors on the LDL lipoprotein surface, allowing their recognition and involvement in

It is also involved in cascade-type metabolic reactions of arachidonic acid and in achieving

Formation of peroxides, especially lipid ones, is a consequence of the activation of O2, the interconversion of reactive species and natural systems protection overcoming. In biological environments, the most favorable substrate for peroxidation is represented by

Peroxidation is a complex process that includes three phases: initiation, propagation, end-decomposition, which interpose, so that only end products can be determined chemically: aldehydes (malondialdehyde), polymerized carbonyl compounds

A radical character initiator (which may have different structures and origins, including peroxy ROO. radicals) removes a hydrogen atom from polyunsaturated fatty acid diallyl

which become hydroperoxides result. In fact, due to side reactions, other locations of the

Since the formation of peroxides and their decomposition products, the sequence of reactions passes from a molecular level to a cellular one due to structural changes that occur in membranes: structural disorganization of the membrane and deterioration of pores crossing the double phospholipid layers. Peroxidation leads to changes in fatty acid qualitative composition of phospholipids composition with changing the ratio between PUFA and other acids. The first two effects induce the third, which consists in a decrease in membrane fluidity and altered active ion transport; these effects finally lead to changes in

Numerous experimental studies have shown that tissue injury caused by free radicals determined at one point an imbalance of Ca2+ (i.e., increases in intracellular Ca2+ concentration). Under physiological conditions, there are effective homeostatic mechanisms (enzyme systems, protein transporters) to keep an optimum ratio between intracellular (0.1- 0.4 microM) and extracellular of the mM order concentration. Overcoming these mechanisms (in this case by producing free radicals) determines the accumulation of

polyunsaturated fatty acids (PUFA), components of cell and subcellular membranes.

carbon, forming a favorable reactive center for oxygen action. The peroxy ROO.

cells, skin fibroblasts and endothelial cells [27].

platelet adhesion and aggregation function.

peroxide group per PUFA molecule occur [28].

ion and other intracellular compounds concentration [26].

**5.3. Cell structural alterations** 

atherogenesis [10, 12].

**5.2. Lipid peroxidation** 

(lipofuscin) [9].

Oxidative stress is an ongoing process in the body, and under physiologic conditions there are effective mechanisms that negate its effects, thus high concentration of erythrocyte GSH and related enzyme equipment provide a defense against ROS.

Erythrocyte congenital enzyme deficiencies confer erythrocytes an increased sensitivity to OS.

A section of the body intensely studied to assess OS is the liver due to its role in the metabolism of a wide range of endogenous and exogenous products. Thus, by the metabolism of aromatic compounds, drugs or carcinogenic hydrocarbons in the live, a large amount of FR occurs, which will initiate in the next phase OS from this level.

Liver antioxidant systems are represented by SOD, GSH and dependent enzymes (transferase and peroxidase). Using ESR and spin trapping, FR resulting from chemical pollutants metabolism were identified, and a strong correlation between the functional impairment of the hepatic parenchyma, free radicals formation and decrease in GSH was noted. Under these conditions, free radicals of that substance occur which can cause tissue destructions also without O2 activation.

The experimental poisoning of rats with alcohol (1.5 mmol/kg) showed significant decrease at one hour of ingestion of GSH, vitamin E and C along with hepatic necrosis and formation of lipid peroxides [2, 11].

GSH is an important protective factor against OS. Its level is interrelated with other antioxidants (vitamin C and E) that stimulate its preservation in reduced form.

*Stress proteins*. Structurally altered intracellular protein group, whose synthesis is induced by oxidative stress has been named stress proteins group. Of particular interest is the 32 kDa protein whose synthesis is induced by the action of ionizing radiation, hydrogen peroxide. This protein is a marker of generalized response to oxidative stress. Free radicals affect cytokines (endogenous pyrogens: IL-1, IL-2, TNF-a, IFN) that play a role in regulating signal transmission in response to stress which will cause the synthesis of these proteins. It is considered that SOD itself is a stress protein.

The tissue repair process is enzymatically catalyzed (repair enzymes) that break down damaged cellular particles, take intact aminoacids to synthesize new defense proteins.
