215
[ 123 – 125 ]. Although not fully understood, this transient increase has been
suggested to be mediated through rigorous cardiac contractions which increase the
flow of electrons through the electron transport chain and formation of O 2 •. It
seems that this burst of ROS is critical in the cardiac response to exercise. In line
with this, the beneficial cardiac responses in rodents [ 126 ] as well as health pro-
moting effects of exercise in humans [ 127 ] have been impaired on antioxidant
therapies. Prolonged acute exercise increases ROS production, uncoupled respira-
tion and mitochondrial membrane potential in mitochondria isolated from rat
hearts as described by Bo et al. [ 124 ]. Continued exercise resulted in normalization
of the mitochondrial ROS levels.
6.3 Benefits of Exercise on NADPH Oxidase-Dependent ROS
Production
NADPH oxidases (NOXs) represent a major source of ROS in cardiomyocytes
[ 128 ]. NOXs generate ROS physiologically as a mean of cellular defense against
pathogens [ 129 ]. NOX2 and NOX4 are the primary cardiac isoforms [ 130 ] that
Fig. 12.2 Superoxide (O 2 •) production through electron transport chain leakage. Under hypergly-
cemic conditions, the electron transport chain become saturated and electrons are forced to be
transferred to oxygen and generates O 2 •. NAD nicotinamide adenine dinucleotide, FA D flavin
adenine dinucleotide, SOD superoxide dismutase, GPx glutathione peroxidase
12 Exercise Amaliorates Metabolic Disturbances and Oxidative Stress in Diabetic...