Markers of oxidative stress in erythrocytes and plasma during aging in humans

Abstract

Aging is an inevitable universal biological process, which can be characterized by a general decline in physiological function with the accumulation of diverse adverse changes and increased probability of death. Among several theories, oxidative stress/free radical theory offers the best mechanistic elucidation of the aging process and other age -related phenomenon. In the present paper , we discuss the aging process and have focused on the importance of some reliable markers of oxidative stress which may be used as biomarkers of the aging process.

Figure 1

Reactive oxygen species (ROS) generated by endogenous as well as exogenous sources, cause damage and accumulation of proteins, lipids and DNA s, when defensive (repair) mechanisms of body become weak. These ROS also modulate the signal transduction pathways. These disturbances cause organelle damage, changes in gene expression followed by altered cellular responses which ultimately results into aging.

Figure 2

Development of oxidative stress in erythrocytes. Hb; hemoglobin, SOD; superoxide dismutase, CAT; catalase. Under normal conditions, reactive oxygen radicals are buffered by endogenous defensive enzymes i.e., superoxide dismutase and catalase but due to reduced reducing/antioxidant capacity during aging or in other pathological conditions, reactive oxygen radicals escape and destroy the macromolecules, which ultimately results in altered erythrocytic behavior.

Figure 3

Pathways of free radical mediated lipid peroxidation, proceeds by a chain mechanism, that is, one initiating free radical can oxidize many molecules of lipids. Chain progression is carried by lipid peroxyl radicals independent of the type of chain-initiating free radicals. The major reactions include abstraction of bisallylic hydrogen from polyunsaturated fatty acids to give carboncentered radicals which rearranges to more stable cis,trans-pentadienyl radicals, addition of oxygen to the pentadienyl radical to give lipid peroxyl radicals, release of oxygen from the peroxyl radical to give oxygen and pentadienyl radicals, which rapidly react with oxygen to give a thermo chemically more stable trans, trans form preferentially than cis, trans form and intramolecular addition of the peroxyl radical to the double bond to yield bicyclic prostaglandin-type products. The important chain propagation step is the abstraction of bisallylic hydrogen from lipids by lipid peroxyl radicals to give conjugated diene lipid hydroperoxide and new lipid radicals, which continues another chain reaction (Niki et al. 2009).

Figure 4

Schematic representation of ascorbate (ASC) recycling between erythrocytes and plasma. Under normal conditions, the plasma membrane redox system (PMRS) and ascorbate free radical (AFR) reductase function to transfer reducing equivalents from intracellular electron donors to plasma. These electrons are used to reduce the AFR to reduced ASC. During aging, the condition of oxidative stress is generated in the plasma, leading to higher rate of conversion of ASC to AFR. The increase in erythrocyte AFR reductase/PMRS activity is a compensatory mechanism to protect against increased oxidative stress (Rizvi et al. 2009).

Figure 5

Superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and catalase (CAT) are the main endogenous enzymatic defense systems of all aerobic cells. They give protection by directly scavenging superoxide radicals and hydrogen peroxide, converting them to less reactive species. SOD catalyzes the dismutation of superoxide radical (•O₂) to hydrogen peroxide (H₂O₂). Although H₂O₂ is not a radical, it is rapidly converted by fenton reaction into •OH radical which is very reactive. GPx neutralizes hydrogen peroxide by taking hydrogens from two GSH molecules resulting in two H₂O and one GSSG. GR then regenerates GSH from GSSG. CAT the important part of enzymatic defense, neutralizes H₂O₂ into H₂O.

Figure 6

Status of important biomarkers of oxidative stress during aging is shown. AFR reductase; ascorbate free radical reductase, PMRS; plasma membrane redox system, HNE ; 4-hydroxy-2,3-trans-nonenal, 8OHdG; 8-Hydroxy-2′deoxyguanosine, GSSG-R; glutathione reductase, GSH-S-T; glutathione S-transferase, SOD; superoxide dismutase, CAT; catalase.