To study the role of Kupffer cells (KC) as a cellular source of proinflammatory cytokines in hepatic ischemia/reperfusion, Sprague-Dawley rats were subjected to 20 min global hepatic ischemia. Sham-operated animals served as controls. Blood levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha), and interleukin 6 (IL-6) were determined after 10, 30, 60, 120, and 240 min of reperfusion and compared with spontaneous cytokine release by KC isolated after 60 min of reperfusion. Hepatic ischemia/reperfusion resulted in an enhanced (p < .01) spontaneous release of TNF-alpha (+482%), IL-1 alpha (+33%), and IL-6 (+175%) by KC. Kinetic analysis of cytokinemia revealed an early increase (p < .01) of TNF-alpha and IL-1 alpha within minutes upon reperfusion, while an elevation of IL-6 serum levels was observed with a delay of 2 h. Early cytokinemia was associated with dysfunction/injury of the liver, lung, and kidney after 4 and 24 h of reperfusion, respectively. These data indicate that hepatic ischemia/reperfusion results in Kupffer cell activation and increased cytokine levels, which may produce systemic inflammation and may be responsible for tissue injury locally and on remote sites.
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http://dx.doi.org/10.1097/00024382-199601000-00008 | DOI Listing |
Naunyn Schmiedebergs Arch Pharmacol
January 2025
Department of Physiology, College of Medicine, King Saud University, 12271, Riyadh, Saudi Arabia.
Ischemia-reperfusion injury (IRI) is a common pathogenic situation that arises throughout all liver surgeries, including liver transplants. We aimed to compare the preventive effects of valsartan (VST) against valsartan + sacubitril (LCZ696) on hepatic injury caused by IRI. A total of thirty-six male Westar albino rats were split into six groups randomly: sham, IRI, VST + IRI, LCZ696 + IRI, VST, and LCZ696.
View Article and Find Full Text PDFJ Hepatol
January 2025
Department of Minimal Invasive Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China; Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, China; Lead contact. Electronic address:
Background & Aims: Hepatic ischemia‒reperfusion injury (HIRI) is a critical complication of liver surgery and transplantation that contributes significantly to severe organ failure. GRINA, a calcium-regulating endoplasmic reticulum (ER) protein, plays an essential role in controlling the unfolded protein response; however, its role in HIRI remains unclear. The aim of this study was to investigate the function of GRINA in HIRI and explore its potential as a therapeutic target.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
Liver Transplant Center, Transplant Center, West China Hospital, Sichuan University, Chengdu, 610041, China.
Recipients often suffer from hyperlactatemia during liver transplantation (LT), but whether hyperlactatemia exacerbates hepatic ischemia-reperfusion injury (IRI) after donor liver implantation remains unclear. Here, the role of hyperlactatemia in hepatic IRI is explored. In this work, hyperlactatemia is found to exacerbate ferroptosis during hepatic IRI.
View Article and Find Full Text PDFCurr Top Med Chem
January 2025
College of Sports Medicine and Rehabilitation, Shandong First Medical University & Shandong Academy Medical Sciences, 619 Changcheng Road, Taian 271016 Shandong, PR China.
Background And Objective: Hepatic ischemia reperfusion injury (HIRI) is a common complication closely related to the prognosis of liver surgery, and effective treatment methods are still unavailable. SRT1720 has the characteristics of multifunction and multitarget which may cope with the multidirectional complex pathological process caused by HIRI. The present study aimed to explore the potential mechanism of SRT1720 in HIRI through a combination of network pharmacology, in vitro experiments and in vivo models.
View Article and Find Full Text PDFNaunyn Schmiedebergs Arch Pharmacol
January 2025
Gastroenterology and Hepatology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran.
Intestinal ischemia-reperfusion injury (IIR/I) significantly increases morbidity and mortality. This study examines the therapeutic effects of geraniol (GNL), which is noted for its anti-inflammatory and antioxidant properties, on intestinal I/R injury in rats. Forty-nine male Wistar-Albino rats were divided into seven groups.
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