The Heme Oxygenase System: Its Role in Liver Inflammation

Wunder, Christian; Potter, Richard F.

doi:10.2174/1568006033481410

Cited by 82 publications

(74 citation statements)

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“…The mechanism by which HO-1 confers protection against oxidative stress has not yet been fully understood. It has been suggested that HO-1 possesses antioxidant activity deriving from the elimination of prooxidant heme and from the biological activities of its reaction products: biliverdin, bilirubin and iron [22][23][24] . Both biliverdin and bilirubin possess antioxidant properties [25] , whereas iron released during heme catabolism can stimulate ferritin synthesis [26] .…”

Section: Basic Researchmentioning

confidence: 99%

Heme oxygenase-1 overexpression increases liver injury after bile duct ligation in rats

Froh

Conzelmann²,

Walbrun³

et al. 2007

WJG

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AIM:To investigate the effects of heme oxygenase-1 (HO-1) against oxidant-induced injury caused by bile duct ligation (BDL). METHODS:Either cobalt protoporphyrin (CoPP), a HO-1 inducer, or saline were injected intraperitoneally in male SD-rats. Three days later, BDL or sham-operations were performed. Rats were sacrificed 3 wk after BDL and livers were harvested for histology. Fibrosis was evaluated by sirius red staining and image analysis. Alpha-smooth muscular actin, which indicates activation of stellate cells, was detected by immunohistochemical staining, and cytokine and collagen-Ⅰα (Col-Ⅰα) mRNA expression was detected using RNase protection assays. RESULTS:Serum alanine transaminase increased 8-fold above normal levels one day after BDL. Surprisingly, enzyme release was not reduced in rats receiving CoPP. Liver fibrosis was evaluated 3 wk after BDL and the sirius red-positive area was found to be increased to about 7.8%. However, in CoPP pretreated rats sirius redpositive areas were increased to about 11.7% after BDL. Collagen-Ⅰα and TGF-β mRNA increased significantly by BDL. Again, this effect was increased by HO-1 overexpression.

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Section: Basic Researchmentioning

confidence: 99%

Heme oxygenase-1 overexpression increases liver injury after bile duct ligation in rats

Froh

Conzelmann²,

Walbrun³

et al. 2007

WJG

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“…[13][14][15][16] Accumulating evidence reveals the protective role of HO-1 by virtue of the antiinflammatory, antiapoptotic and antiproliferative activities of the products released by the heme breakdown reaction. [17][18][19] The acute phase response (APR) is a defense reaction of the organism directed to restrict the area of damage and to eliminate, or at least isolate, the damaging agent. Every agent that leads to loss of tissue integrity induces a local reaction known as inflammation.…”

mentioning

confidence: 99%

Upregulation of heme oxygenase-1 gene by turpentine oil-induced localized inflammation: involvement of interleukin-6

Tron¹,

Novosyadlyy²,

Dudás³

et al. 2005

Laboratory Investigation

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Heme oxygenase-1 (HO-1) is the inducible isoform of an enzyme family responsible for heme degradation and was suggested to be involved in the acute phase response in the liver. However, the mechanisms of the HO-1 regulation under inflammatory conditions are poorly understood. Therefore, the purpose of the current work was to study the expression of HO-1 in the liver and other organs of rats with a localized inflammation after intramuscular injection of turpentine oil (TO). Since interleukin-6 (IL-6) is known to be a principal mediator of inflammation, the levels of this cytokine were also estimated in the animal model used. HO-1 and IL-6 expression was evaluated by Northern blot, in situ hybridization, Western blot, immunohistochemistry and enzyme-linked immunosorbent assay. In the liver and injured muscle, the HO-1 mRNA levels were dramatically increased 4-6 h after TO administration. HO-1 protein levels in the liver were elevated starting from 6-12 h after the treatment. In other internal organs such as the heart, kidney and large intestine, only a slight induction of HO-1 mRNA was observed. IL-6-specific transcripts appeared only in the injured muscle and were in accordance with serum levels of IL-6. In turn, temporal expression of IL-6 in the muscle and circulatory IL-6 levels correlated well with HO-1 expression in the liver and injured muscle. In the liver of control rats HO-1 protein was detected in Kupffer cells, while in TO-injected rats also hepatocytes became strongly HO-1 positive. Conversely, in the injured muscle, HO-1 immunoreactivity was attributed only to macrophages. Our data demonstrate that during localized inflammation HO-1 expression was rapidly and strongly induced in macrophages of injured muscle and in hepatocytes, and IL-6 derived from injured muscle seems to be responsible for the HO-1 induction in the liver.

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“…HO-1 catabolizes free heme into CO, biliverdin, and iron (20,21). According to many animal studies, HO-1 has protective effects against oxidative stress (22)(23)(24).…”

Section: Discussionmentioning

confidence: 99%

Heme breakdown and ischemia/reperfusion injury in grafted liver during living donor liver transplantation

et al. 2011

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Abstract. Living donor liver transplantation (LDLT) requires ischemia/reperfusion (I/R), which can cause early graft injury. However, the detailed mechanism of I/R injury remains unknown. Heme oxygenase-1 (HO-1) is a rate-limiting enzyme in heme catabolism and results in the production of iron, carbon monoxide (CO), and biliverdin IXα. Furthermore, in animals, HO-1 has a protective effect against oxidative stress associated with I/R injury. However, in humans, the molecular mechanism and clinical significance of HO-1 remain unclear. We previously demonstrated that exhaled CO levels increase during LDLT, and postulated that this may indicate I/R injury. In this study, we elucidate the origin of increased exhaled CO levels and the role of HO-1 in I/R injury during LDLT. We studied 29 LDLT donors and recipients each. For investigation of HO-1 gene expression by polymerase chain reaction and HO-1 localization by immunohistological staining, liver biopsies from the grafted liver were conducted twice, once before and once after I/R. Exhaled CO levels and HO-1 gene expression levels significantly increased after I/R. In addition, HO-1 levels significantly increased after I/R in Kupffer cells. Furthermore, we found a significant positive correlation between exhaled CO levels and HO-1 gene expression levels.These results indicated that increased heme breakdown in the grafted liver is the source of increased exhaled CO levels. We also found a significant relationship between HO-1 gene expression levels and alanine aminotransferase (ALT) levels; i.e., the higher the HO-1 gene expression levels, the higher the ALT levels. These results suggest that HO-1-mediated heme breakdown is caused by I/R during LDLT, since it is associated with increased exhaled CO levels and liver damage.

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The Heme Oxygenase System: Its Role in Liver Inflammation

Cited by 82 publications

References 0 publications

Heme oxygenase-1 overexpression increases liver injury after bile duct ligation in rats

Heme oxygenase-1 overexpression increases liver injury after bile duct ligation in rats

Upregulation of heme oxygenase-1 gene by turpentine oil-induced localized inflammation: involvement of interleukin-6

Heme breakdown and ischemia/reperfusion injury in grafted liver during living donor liver transplantation

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