1. Anti-CD163-dexamethasone protects against apoptosis after ischemia/reperfusion injuries in the rat liver
- Author
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Kasper Jarlhelt Andersen, Anders Riegels Knudsen, Jens R. Nyengaard, Pia Svendsen, Jonas Heilskov Graversen, Søren K. Moestrup, Frank Viborg Mortensen, Stephen Hamilton-Dutoit, Lin Nanna Okholm Møller, Holger Jon Møller, and Elise Marie Okholm Møller
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Pathology ,medicine.medical_specialty ,MP, methylprednisolone ,Ischemia ,Aspartate transaminase ,Ischemia/reperfusion injury ,Pharmacology ,HE, hematoxylin & eosin ,Dexamethasone ,ROS, reactive oxygen species ,AST, aspartate transaminase ,ALT, alanine aminotransferase ,medicine ,GGT, gamma-glutamyl transferase ,HDD, high-dose dexamethasone ,Interleukin 6 ,Receptor ,LDD, low-dose dexamethasone ,TNF-α, tumor necrosis factor α ,Original Research ,biology ,business.industry ,Inflammatory response ,General Medicine ,medicine.disease ,IRI, ischemia/reperfusion injury ,IL-1, interleukin 1 ,Hp, haptoglobin ,BR, bilirubin ,IL-6, interleukin 6 ,Anti-CD163-dex, anti-CD163-dexamethasone ,AP, alkaline phosphatase ,Liver ,CD-163 ,Apoptosis ,biology.protein ,PM, pringles maneuver ,Surgery ,SURS, systematic, uniform, random sampling ,business ,NVR, necrotic volume ratio ,CD163 ,Reperfusion injury ,medicine.drug - Abstract
Aim The Pringle maneuver is a way to reduce blood loss during liver surgery. However, this may result in ischemia/reperfusion injury in the development of which Kupffer cells play a central role. Corticosteroids are known to have anti-inflammatory effects. Our aim was to investigate whether a conjugate of dexamethasone and antibody against the CD163 macrophage cell surface receptor could reduce ischemia/reperfusion injury in the rat liver. Methods Thirty-six male Wistar rats were used for the experiments. Animals were randomly divided into four groups of eight receiving anti-CD163-dexamethasone, high dose dexamethasone, low dose dexamethasone or placebo intravenously 18 h before laparotomy with subsequent 60 min of liver ischemia. After reperfusion for 24 h the animals had their liver removed. Bloods were drawn 30 min and 24 h post ischemia induction. Liver cell apoptosis and necrosis were analyzed by stereological quantification. Results After 24 h' reperfusion, the fraction of cell in non-necrotic tissues exhibiting apoptotic profiles was significantly lower in the high dose dexamethasone (p = 0.03) and anti-CD163-dex (p = 0.03) groups compared with the low dose dexamethasone and placebo groups. There was no difference in necrotic cell volume between groups. After 30 min of reperfusion, levels of haptoglobin were significantly higher in the anti-CD163-dex and high dose dexamethasone groups. Alanine aminotransferase and alkaline phosphatase were significantly higher in the high dose dexamethasone group compared to controls after 24 h' reperfusion. Conclusions We show that pharmacological preconditioning with anti-CD163-dex and high dose dexamethasone reduces the number of apoptotic cells following ischemia/reperfusion injury., Highlights • We investigated the effect of pharmacologic preconditioning with HDD, LDD and anti-CD163-dex on ischemia/reperfusion injury. • Liver cell apoptosis and necrosis were analyzed by stereological quantification. • Anti-CD163-dex and high dose dexamethasone reduces the number of apoptotic cells following ischemia/reperfusion injury.
- Published
- 2015
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