Z Gastroenterol 2012; 50(1): 34-40
DOI: 10.1055/s-0031-1282046
© Georg Thieme Verlag KG Stuttgart · New York

The Multiple Functions of Heme Oxygenase-1 in the Liver

Die Bedeutung der Hämoxygenase-1 bei Lebererkrankungen
G. Sass
R. Barikbin
G. Tiegs
Further Information

Publication History

17 October 2011

02 December 2011

Publication Date:
05 January 2012 (online)


Heme oxygenases (HO) are essential enzymes which degrade heme into carbon monoxide (CO), biliverdin and free iron. Due to its anti-inflammatory, anti-apoptotic and, as recently described, anti-viral properties the inducible HO isoform HO-1 is an important molecule which could find its way into therapy of gastrointestinal diseases. Acute and chronic liver injuries including acute liver failure, alcoholic or viral hepatitis, chronic inflammation, fibrosis, cirrhosis, and hepatocellular carcinoma are life threatening diseases and as a consequence might result in the necessity of liver transplantation. HO-1 as well as its reaction products of heme degradation has been linked to cytoprotection. HO-1 induction in rodent models of acute and chronic hepatic inflammation resulted in improvement of liver damage and down-regulation of pro-inflammatory cytokine levels. Furthermore HO-1 induction interfered with fibrosis progression in mice and partially resolved existing fibrosis. Likewise, HO-1 induction interfered with replication of hepatitis viruses B and C, which frequently are the reason for chronic hepatitis and subsequent tumor growth. Liver transplantation is limited by ischemia/reperfusion (I/R) injury, which is characterized by hypoxia and nutrient deficiency resulting in oxidative stress, apoptosis and immune activation. Induction of HO-1 and application predominantly of CO have been shown to interfere with I/R liver injury and to improve recipient and graft survival. On the other hand HO-1 has been shown to be over-expressed in various tumors, including hepatocellular carcinoma (HCC). Due to its anti-apoptotic properties this bears the risk to promote tumor growth. Anti-apoptotic effects are predominantly mediated by CO. This review aims to summarize beneficial as well as detrimental effects of HO-1 and its products within the liver.


Hämoxygenasen (HO) sind essenzielle Enzyme, die Häm zu Kohlenmonoxid, Biliverdin und freiem Eisen abbauen. Aufgrund der antientzündlichen, antiapoptotischen und der erst kürzlich beschriebenen antiviralen Eigenschaften der einzigen induzierbaren Hämoxygenase-Isoform, der HO-1, birgt dieses Molekül ein großes therapeutisches Potenzial in Bezug auf gastrointestinale Erkrankungen in sich. Akute und chronische Lebererkrankungen, wie bspw. akutes Leberversagen, alkoholische oder virale Hepatitis, eine mögliche hieraus resultierende chronische Entzündung, Fibrose, Zirrhose und hepatozelluläres Karzinom stellen lebensbedrohliche Erkrankungen dar, in deren Folge eine Lebertransplantation unumgänglich sein kann. HO-1, aber auch deren Abbauprodukte wurden als hepatoprotektiv beschrieben. So führte die Induktion der HO-1 in Mausmodellen zu einer Hemmung akuter Leberentzündungen verbunden mit einer Reduktion proinflammatorischer Zytokine. Im Modell einer chronischen Leberentzündung wirkte HO-1-Induktion antifibrotisch. Hepatitis B und C Virus Infektionen führen oft zu chronischer Leberentzündung und können die Entstehung des hepatozellulären Karzinoms begünstigen. Interessanterweise hemmen HO-1 sowie deren Produkt Biliverdin die Replikation dieser Viren. Der Erfolg einer Lebertransplantation ist durch Ischämie/Reperfusionsschäden limitiert, die durch oxidativen Stress, Entzündung und hepatozelluläre Apoptose charakterisiert sind. Die Induktion von HO-1 sowie die Applikation von Kohlenmonoxid konnten Ischämie/Reperfusionsschäden verringern und das Überleben des Transplantats und des Transplantatempfängers selbst verlängern. Andererseits konnte gezeigt werden, dass HO-1 in verschiedenen Tumoren, inklusive Lebertumoren, häufig überexprimiert vorliegt. Die hauptsächlich durch Kohlenmonoxid vermittelte antiapoptotische Funktion der HO-1 könnte in diesem Fall das Tumorwachstum unterstützen. Dieser Review-Artikel soll einen Überblick über positive sowie negative Eigenschaften der HO-1 und ihrer Produkte in der Leber geben.

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