History of Biomarkers - Ecological Biomarkers: Indicators of Ecotoxicological Effects - page 23

2.3.6 Enzymatic and Nonenzymatic Antioxidant Defenses

In biological systems, reactive oxygen species (ROS) are continuously produced by several
mechanisms involving exo- or endogenous compounds such as xenobiotics (Di Giulio et
al. 1989; Livingstone et al. 1990; Winston and Di Giulio 1991). In aerobic organisms, they
are part of basal cellular metabolism such as cellular respiration or phagocytosis activity
(Cossu et al. 1997; Valavanidis et al. 2006). Their production is also a result of the activity of
different oxidative enzymes such as tryptophan dioxygenase, xanthine oxidase, and cyto-
chrome P450 reductase that produce superoxide anions, and guanyl cyclase and glucose
oxidase, which are able to generate hydrogen peroxide.
Moreover, chemical pollutants are important producers of ROS. The xenobiotics known
for their redox properties such as quinones, transition metals, diazoïc staining, bipyridyl
herbicides, and nitric aromatic compounds induce the formation of superoxide radicals.
The imbalance in favor of ROS production instead of their neutralization by antioxidant
systems corresponds to oxidative stress. At the cellular level, it results in the alteration and
more particularly in the oxidation of components such as DNA, proteins, and lipids and
in a total disturbance of the redox balance (e.g., ratios GSH/GSSG and NADH/NAD + ). Its
cytotoxic effects are expressed by structural and functional perturbations such as enzy-
matic inhibition, protein damage, lipid peroxidation, inflammatory processes, and apop-
tosis (Figure 2.2).
During evolution, aerobic organisms have developed antioxidant defense mechanisms
whose main function is to block off and to deactivate ROS. The extent of oxidative damage
is directly related to the efficiency of antioxidant systems occurring in the different species.
The systems are composed of a suite of cytosolic enzymes [mainly superoxide dismutases
(SODs), peroxidases, catalases], reducing molecules of low molecular weight (glutathione,
ascorbates, urates) and several liposoluble vitamins (α-tocophérol, β-carotene).
Among enzymatic antioxidant systems, SODs correspond to a metallo-enzyme family
(containing Cu, Zn, Fe, or Mn) known to convert superoxide anion in hydrogen peroxide,
H 2 O 2 . Among peroxidases, glutathione peroxidase (GPx), depending or not on selenium,

Environmental stress

ROS

Lipid peroxidation

Antioxidant defense
systems

DNA damage

Aldehydes among
them MDA

Defense and damage
biomarkers

FIGURE 2.2
Environmental stress in organisms could generate ROS able to induce damage to membrane lipids and DNA
molecules but also to antioxidant defenses. The cellular damage and the induction of defense systems could be
used as defense or damage biomarkers.