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.