Ischaemic postconditioning reduces peroxide formation, cytokine expression and leukocyte activation in reperfusion injury after abdominal aortic surgery in rat model

Abstract

Objective: We studied the protective effects of ischaemic postconditioning (PS) on ischemia-reperfusion injury of the lower extremities in a rat model of abdominal aortic intervention. We aimed to examine the evoked oxidative stress, cytokine expression and leukocyte activation after revascularisation surgery.Methods: Anesthetized animals (48 Whistar rats) underwent a 60 min infrarenal aorta cross-clamping. After the ischaemic period, an intermittent 4 times 15 s reperfusion -15 seconds ischaemic episodes -were applied (ischaemic postconditioning: group PS). Then we started a 120 min reperfusion in the aorta. In untreated group animals underwent a long ischaemia (60 min) and the following reperfusion (group IR). Peripherial blood samples were collected before operation, and in early (5, 10, 15, 30, 60 and 120 min) reperfusion periods. Serum peroxide level, TNF-alpha concentration, myeloperoxidase (MPO) activity and PMA-induced leukocyte ROS production were measured.Results: In PS group, plasma peroxide level elevation was significantly lower in very early reperfusion (5-30 min) comparing to non-conditioned IR group (10.04 ± 1.9 µM/l vs. 16.91 ± 3.67 µM/l, p < 0.05). PS also reduced serum TNF-alpha concentration (167.41 ± 31.26 µg/ml vs. 116.55 ± 12.04 µg/ml, p < 0.05), MPO activity (1.759 ± 0.239 µM/ml vs. 1.22 ± 0.126 µM/ml, p < 0.05) and leukocyte activation detected by PMA-induced leukocyte ROS production (5.7 ± 0.96 AU/10 3 cells vs. 4.63 ± 0.69 AU/10 3 cells).Conclusions: Ischaemic postconditioning could reduce ROI production after IR in early reperfusion period, thus limiting ROI mediated tissue lesion, cytokine-leukocyte activation and inflammatory responses. PS seems to be an effective tool in vascular surgery to reduce reperfusion injuries after revascularization interventions.

Inhibition of tumor necrosis factor alpha reduces the outgrowth of hepatic micrometastasis of colorectal tumors in a mouse model of liver ischemia-reperfusion injury

“…Furthermore, development of IR has been shown to cause a remarkable increase in the serum level of tumor necrosis factor alpha (TNF-α), mainly through release from activated Kupffer cells [ 9 , 10 ]. Other studies have shown TNF-α to further induce cytokines and production of granulocyte colony-stimulating factor, which in turn further enhance Kupffer cell activation and promote neutrophil infiltration in the liver [ 11 , 12 ].…”

Combined Preconditioning and Postconditioning Provides Synergistic Protection against Liver Ischemic Reperfusion Injury

“…Shortly after the hepatic ischemia and reperfusion injury (1-6 hours), the Kupffer cells are activated and release the pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF α) and interleukin-1 beta (IL-1β). These cytokines have dual role: over range expression of TNFα and IL-1β can induce more production of cytokines and granulocyte colony-stimulating factor, which enhance Kupffer cells activation and promote neutrophil infiltration in microcirculation of liver 6 , 7 , then aggravate hepatic sterile inflammation after ischemia and reperfusion. On the other hand, TNFα and IL-1 are indispensable for liver regeneration 8 .…”

Indispensable role of β-arrestin2 in the protection of remifentanil preconditioning against hepatic ischemic reperfusion injury

“…KC is the major source of oxidative stress substrates in response to ischemic injury 21,22 , releasing inflammatory cytokines, such as TNF-α and IL-β, which contributes to ischemic hepatocytes injury. It’s well known that LPS can induce TLR4 activation followed by inflammatory cytokine release 23,24 , which also results in KCs activation and hepatic inflammatory injury 25 .…”