Dorn, Christoph and Massinger, Sabine and Wuzik, Andreas and Heilmann, Joerg and Hellerbrand, Claus (2013) Xanthohumol suppresses inflammatory response to warm ischemia-reperfusion induced liver injury. EXPERIMENTAL AND MOLECULAR PATHOLOGY, 94 (1). pp. 10-16. ISSN 0014-4800,
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Liver ischemia/reperfusion (I/R) leads to formation of reactive oxygen species (ROS), which cause hepatic injury and initiate an inflammatory response, which is a critical problem after liver surgery and transplantation. Xanthohumol, the major prenylated chalcone found in hops, has been discussed for its anti-inflammatory and ROS-scavenging properties, and thus, we aimed to investigate the effect of xanthohumol in a model of warm I/R liver injury. Xanthohumol was applied to BALB/c mice orally at a dose of 1 mg/g body weight for 5 days before I/R-injury was induced by clamping the vascular blood supply to the median and left lateral liver lobe for 1 h followed by a 6 h period of reperfusion. At this time, HPLC analysis revealed hepatic xanthohumol levels of approximately 2 mu M, a concentration which has been shown to inhibit inflammatory effects in vitro. Assessment of hepatic HMOX1 expression, hepatic glutathione content and immunohistochemical analysis for proteins conjugated with the reactive aldehyde 4-hydroxynonenal indicated that I/R-induced oxidative stress was significantly inhibited in xanthohumol-fed compared to control mice. Histological analysis, TUNEL staining and determination of transaminase serum levels revealed no significant effects of xanthohumol on acute hepatocellular injury. However, at the same time point, pretreatment with xanthohumol almost completely blunted the I/R-induced AKT and NFkB activation and the expression of the proinflammatory genes IL-1alpha, IL-6, MCP-1 and ICAM-1, which are known to play a crucial role in the subacute phase of I/R-induced liver damage. In conclusion, these data indicate the potential of xanthohumol application to prevent adverse inflammatory responses to I/R-induced liver damage such as after surgical liver resection or transplantation. (C) 2012 Elsevier Inc. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | FACTOR-KAPPA-B; ISCHEMIA/REPERFUSION INJURY; HEPATIC ISCHEMIA; RAT-LIVER; HEPATOCELLULAR-CARCINOMA; HUMULUS-LUPULUS; REACTIVE OXYGEN; KUPFFER CELLS; EXPRESSION; HOPS; Xanthohumol; Inflammation; ROS; NEkB; Liver; Warm ischemia-reperfusion injury |
| Subjects: | 600 Technology > 610 Medical sciences Medicine 600 Technology > 615 Pharmacy |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I Chemistry and Pharmacy > Institute of Pharmacy Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical Biology (Prof. Heilmann) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 27 Apr 2020 05:13 |
| Last Modified: | 27 Apr 2020 05:13 |
| URI: | https://pred.uni-regensburg.de/id/eprint/17203 |
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