Research Information System
in: INFLAMMATION AND in vitro DIAGNOSTICS, KOÇDOR HİLAL,PABUÇÇUOĞLU NEFİSE AYSUN,ZİHNİOĞLU FİGEN, Editor, Turkiye Klinikleri, Ankara, pp.166-169, 2024
ABS TRACT Oxidative stress is a major and recurrent cause of inflammation in organ transplantation. The ischemia-reperfusion damage that occurs during organ transplantations causes emergence of free oxygen radicals and pathological nitrogen products. This increases oxidative stress. Reducing oxidative stress leads to increased consumption of endogenous antioxidants. Depending on the degree of oxidative stress, various degrees of damage may occur in the transplanted organ, and as a result, the function of the graft may be impaired. The decrease in adenosine triphosphate (ATP) level formed during ischemia leads to acidification in the intracellular and extracellular environment. This results in accumulation of sodium and calcium in the intracellular environment. Calcium ion accumulation leads to activation of calcium-dependent proteases, which initiates irreversible cell membrane damage that causes necrosis, apoptosis, and autophagic mechanisms. Especially increase in superoxide radicals and proinflammatory factors, decrease in nitric oxide production and activation of hypoxatine-xanthine oxidase system in the liver increase hepatocellular damage by increasing oxidative stress. While ischemia creates serious tissue damage, reperfusion of the organ can lead to more severe damage. The increase in oxygen levels with reperfusion may contribute to the increase of reactive oxygen products. It has been shown that the main cells that initiate ischemia-reperfusion injury in the liver are Kupfer Cells, and the main mediators are reactive oxygen and reactive nitrogen products. Reactive oxygen products include hydrogen peroxide (H2O2), superoxide anion and hydroxyl radicals. The most biologically relevant reactive nitrogen product is nitric oxide (NO). Activation of Kupfer Cells together with reactive oxygen products causes formation of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1). DNA damage and endothelial dysfunction may also occur during ischemia-reperfusion injury. There is no proven treatment to prevent ischemia-reperfusion injury during reperfusion, other than ischemic preconditioning. During reperfusion, Kupfer Cells stimulate the secretion of CD4+ T lymphocytes; proinflammatory cytokines such as TNF-alpha and IL-1 are activated. Anti-inflammatory cytokines such as IL-4 and IL-10 also work to reduce ischemia-reperfusion injury. Meanwhile, there is a decrease in the levels of many antioxidants. In the late phase of reperfusion, reactive oxygen products and proinflammatory mediators can activate sinusoidal endothelial and CD4+ T cells, and they attract neutrophils to the injury site. Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecules (VCM-1) secreted by endothelial cells increase neutrophil infiltration. Activation of innate immune responses is observed during ischemia-reperfusion injury. As a result, reactive oxygen products from damaged cells and damage associated molecular patterns (DAMP) such as high mobility group box-1 (HMGB-1) and heat shock proteins (HSPs) emerge. These are recognized by Toll-like receptors (TLRs). Activation of signal transduction proteins and transcription factors by TLRs results in the production and release of inflammatory cytokines and chemokines that enhance dendritic cell maturation. N-acetyl cysteine is beneficial in many stages in reducing ischemia-reperfusion injury. In addition, to reduce inflammation in the graft; antiischemic interventions, therapies targeting TLRs and Nuclear factor KappaB, therapies that reduce inflammatory cytokines and adhesion molecules, complement inhibition and antiapoptotic strategies can be used. Transplanted tissues can be rejected as hyperacute, acute and chronic. The most important mechanism in the prevention of rejections is immunosuppression treatments that prevent the activation and functions of T cells. Keywords: Inflammation; organ transplantation; ischemia-reperfusion injury