Free radicals such as superoxide radical or hydroxyl radical are
constantly produced as a normal consequence of aerobic
metabolism
27. Oxidative stress results from an imbalance
between radical generating and radical-scavenging systems
leading to cell membrane impairment or DNA damage
27.
MDA is a reflection of lipid peroxidation, whereas SOD and
GSH-Px are important antioxidant defenses. These enzymes
are involved in the clearance of superoxide and hydrogen
peroxide (H
2O
2) to maintain the structure and function of
biological membranes
27. SOD dismutases superoxide H
2O
2
and this compound is catabolized by catalase and GSH-Px. In
higher organisms, GSH-Px appears to have largely supplanted
the need for catalase membranes
27. Thus, our findings
support the existence of oxidative stress from mechanically
ventilated animals during exposure to sevoflurane. Moreover,
anesthesia conducted with EGCg reduced oxidative stress and
enhanced antioxidant defense mechanisms expressed by larger
concentrations of free radical scavengers.
Oxidative stress leads to the accumulation of lipid
peroxidation products MDA in the heart, and causes impaired
cell function, while antioxidant enzyme SOD and GSH-Px play
great roles in cellular defense against oxidative stress. In this
study, to confirm the presence of increased oxidative stress in
cardiac tissue from mechanically ventilated animals during
exposure to sevoflurane, we quantified myocardial levels of
MDA, NO content, and SOD, GSH-Px and CAT activities. The
results showed that the level of MDA, GSH-Px and SOD in
cardiac tissue increased, while the activities of NO and CAT
was not changed vs the sham-operated control, indicating a
significant oxidative stress. The treatment with EGCg almost
completely prevented the Sevoflurane effects in SOD and
GSH-Px levels, and MDA formation both in cardiac tissue.
These results suggest that the protective effects of EGCg on
cardiac tissue were correlated. EGCg can generate H2O2
28,29, and H2O2 can lead to eNOS activation and
vasorelaxation in aortic rings 27. In a recent study 30
demonstrates that endothelium-dependent vasorelaxation
induced by the tea-derived catechin EGCg occurs in response to a potent, dose-dependent activation of eNOS in endothelial
cells. The resulting increase in eNOS activity is observed
within a few minutes, suggesting posttranslational regulation of
eNOS as an underlying mechanism. In agree with this study,
we also found that level of NO in cardiac tissue incresed with
EGCg supplementation.
Impairment of non-enzymatic antioxidant scavenging
activity is related to elevation of toxic metabolites such as
superoxide free radicals (O2.−), hydrogen peroxide (H2O2), or
hydroxyl radicals (•OH). Elevation of O2.−, which is the
substrate of SOD might be the reason of the higher enzyme
activity. Also H2O2 which is produced by SOD might be the
cause of CAT and GSH-Px production and higher activity of
this enzyme with the same mechanism. In this study, we
observed an elevation of SOD and GSH-Px levels in group I.
Elevation of SOD and GSH-Px activities due to increased
production of free radicals such as O2 .− and •OH were also
observed. However these compansatory mechanisms were not
able to prevent cellular lipid peroxidation. Therefore, these
findings might be as a result of more production of radicals due
to sevoflurane administration. Another finding supporting this
hypothesis is MDA levels which have the highest values in
group 1 Enzymatic findings may be important signs of effects
of administration of sevoflurane and EGCg at the cellular level.
The volatile anaesthetic sevoflurane protects the heart
against ischaemia-induced adenosine triphosphate (ATP)
depletion, Ca2+ overload and oxidative stres through activation
of protein kinase C (PKC), opening of mitochondrial K+ ATP
channels (mitoK+ATP) and the production of ROS (4, 31-33).
But Sevoflurane 34 have been proposed to cause formation of
ROS directly in cardiac tissues. It may be possible that an
anesthetic can cause free radical release from itself or the tissue
with which it interacts.
In conclusion, the amount of lipid peroxidation and
antioxidant enzyme activities were more increased in following
sevoflurane administration in the 3% concentration. The
administration of intravenous EGCg (40 mg/kg/d) significantly
protected cardiac tissue. These conclusions were supported by
the improved reduced levels of MDA.
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