DISCUSSION
Today, abdominal aortic clamping, which is used in cardiovascular
surgery operations, is frequently used. Although vascular clamping
provides surgeons with many working advantages, when the clamping area
is examined, swelling, flattening, loss of intercellular connectivity
and endothelial cell peeling are observed in the endothelial cells20,21. At the same time, it causes damage to the
vascular endothelium and tissues with the ischemia it creates and the
subsequent reperfusion.
Ischemia reperfusion injury is based on free oxygen radicals that emerge
as a result of tissue oxygenation during reperfusion. Necrotic changes
due to the formation of free oxygen radicals can be seen in the
reperfusion tissue. Reactive oxy radicals can be released from many
sources. The most important are the activated neutrophils. In addition,
cytokines (IL-6; IL-8; TNF), platelet activating factor, and
leukotrienes, which are plasma pro-inflammatory agents, also cause
endothelial cell damage to the complementary factors. Pulmonary
vasoconstriction, hypertension, and increased pulmonary vascular
permeability are the most common side effects of impaired endothelial
cell function 22,23. Endothelial cells play a vital
and dynamic role in maintaining vascular hemostasis (current, selective
permeability and cell traffic). These cells are very sensitive for both
ischemia and reperfusion. Prolonged hypoxia causes intracellular volume
increase and cytoskeletal organization disorders with cell membrane
potential changes, ion distribution disorders and decrease in viscosity24. With tissue reperfusion, ischemic endothelial
changes become evident and endothelial dysfunction develops localized in
the I / R area. Morphological changes following prolonged ischemia and
subsequent reperfusion are cellular swelling, membrane depolarization,
pinocytotic vesicle loss, endothelial cell basement membrane separation,
and adhesion of activated leukocytes (especially neutrophils) to the
endothelial cell surface 24,25. The primary indicator
of I / R injury in arterioles is impairment and hyperreactivity in
endothelium-dependent vasodilation. It was observed that
endothelium-dependent arteriolar vasodilation disappeared in the early
period and smooth muscle function in the late period after
ischemia-reperfusion injury. Therefore, reperfusion of tissues is
difficult in prolonged ischemia 25,26. The arteriolar
I/R response varies from tissue to tissue as well. The clinical
reflection of I / R damage in the arterial capillary endothelium is in
the form of increased fluid filtration to the interstitial tissue and a
decrease in the number of capillaries that provide tissue perfusion26. Increased interstitial fluid filtration is due to
an increase in endothelial barrier hydraulic permeability rather than an
increase in intracapillary pressure. After tissue reperfusion, the
decrease in arterial capillaries due to obstruction causes an increase
in I-R damage by further disrupting tissue perfusion. Microvascular
dysfunction mechanisms occur on the basis of leukocyte-endothelial
adhesion. Leukocyte-derived ROS also contributes to this dysfunction.
Therefore, prevention of leukocyte-endothelial adhesion and antioxidant
treatment can reduce microvascular dysfunction 27.
Curcumin is a cardioprotective antioxidant that has lipid-lowering
properties and reduces oxidative stress 10,28-30.
Curcumin also has a protective effect on endothelial dysfunction31. In several ways, curcumin demonstrates its
endothelial protective effect. Decreased NO bioavailability or decreased
NO synthesis increases endothelial dysfunction. Curcumin decreases
endothelial dysfunction by upregulating eNOS during the phase in which
oxidative stress is induced 16. In addition, it
decreases vascular superoxide anion production and enhances this effect
by inhibiting vascular protein kinase C (PKC-bII) 31.
It also functions as a TNF_ alpha blocker through the Nrf-2 / Heme
oxygenase-1 (OH-1) pathway. Thus, by inhibiting oxidative stress and
inflammatory cytokines, it reduces the ROS load and inflammatory damage
in the vascular endothelium 32,33. With all these
mechanisms, Curcumin protects the vascular endothelium and reduces the
remodeling that occurs in the endothelium.
In this study, it has been shown that with curcumin therapy, oxidative
and vascular endothelial cell harm induced by infrarenal abdominal aorta
clamping can be covered. Systemic oxidative stress that occurs during
ischemia and subsequent phases of reperfusion has been minimized through
cross-clamping with curcumin. The fact that the TAC, TOS and OSI values
in the group given curcumin were significantly lower than the control
group confirms this. Although TAC, TOS and OSI values differed between
the groups, two reasons were attributed to the lack of histopathological
changes in the abdominal aortic tissue. The first explanation was deemed
to be that the I/R duration was not long enough. It was reported in some
of the studies that this time was determined to be 120 minutes for I/R34. The second reason is that it is assumed that
abdominal aortic tissue (due to variations in perfusion) is more
resistant than other tissues to I/R injury.
Many studies have been conducted on the protective effects of curcumin.
I / R injury models have been investigated in a wide variety of organ
systems (heart, kidney, lung, intestine, mesentery, liver, skeletal
muscle) in rats 35-38. In the literature, ischemia
reperfusion studies directed towards the aorta are extremely limited.
Therefore, this study gives an idea about the sensitivity of the
abdominal aorta to ischemia / reperfusion and to what extent Curcumin
can protect the vascular endothelium.
The study has several limitations. The first is that Curcumin was given
intraperitoneally, and the effects of oral intake were not seen. Second,
in order to support previous studies, basic biochemical parameters and
histopathological samples from different tissues are not taken with TAC,
TOS, OSI.