il\VOLVEMENT OF RETII\OIC ACID II{ - MSpace at the University of ...

II. Oxidative stress
II.a. Introduction and seneral facts.
Oxygen is prone to producing its reactive forms such as singlet oxygen, hydrogen
peroxide and hydroxyl radicals. These species, formed by partial reduction of oxygen
molecule, can damage DNA structure, structural proteins, carbohydrates? enzymes and
components of lipid membranes and can ultimately lead to necrosis and apoptosis in
affected tissues. These chemical species include a highly reactive superoxide (Oz'-),
hydrogen peroxide (H2Oz) and hydroxyl (OH') radicals. Due to their high reactivity, most
of the reactive oxygen species (ROS) react with local molecules in the proximity of their
production sights causing the damage to adjacent cellular structures. However, some of
oxygen free radicals such as hydrogen peroxide, have relatively longer half lives and can
diffuse away from their generation sights thus producing a damage in more distant
structures (Fantone and'Ward 1 985).
Over the last two decades it has became clear that free radicals are critical mediators
of pathological processes in the cardiovascular system such as: hypertrophy and
congestive heart failure (Hill and Singal 1996; Singal and Iliskovic i998), ischemia and
reperfusion injury (Slezak et al. t995; van Jaarsveld et al. 1994), coronary artery disease
(McMurray et al. 1990; Prasad and Kalra 7993), diabetic cardiomyopathy (Slezak et al.
1995), and adriamycin-induced cardiomyopathy (Doroshow 1983; Singal et aL 1997;
Singal and Iliskovic 1998).
II.b. Molecular mechanisms of free radical iniurv
Oxidative stress-induced damage to the cells is caused by the reaction of oxygen
free radicals with a number of bio-molecules. Oxidative stress-induced modification of
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