Anti-CD163-dexamethasone protects against apoptosis after ischemia/reperfusion injuries: An experimental study in rats (original) (raw)

Intraoperative blood loss is a major concern during liver surgery. Pringles maneuver is one way to reduce blood loss. This method however may result in ischemia/reperfusion injury (IRI). Kupffer cells play a central role in the development of IRI. Corticosteroids are known to have anti-inflammatory effects. Our aim was to investigate whether a newly developed conjugate of dexamethasone and antibody against the CD163 macrophage cell surface receptor could reduce IRI in the rat liver. Methods: Thirty-six male Wistar rats were randomly divided into four groups of eight rats: 1) anti-CD163dexamethasone (anti-CD163-dex), 2) high dose dexamethasone (HDD), 3) low dose dexamethasone (LDD) or 4) placebo. All rats were subjected to 60 minutes of partial liver ischemia followed by 24 hours of reperfusion. Blood and liver tissue were sampled for further analysis. Liver cell apoptosis and necrosis were analyzed using stereological quantification. Results: After 24 hours' reperfusion, the fraction of apoptotic cell profiles was significantly lower in the HDD (p = 0.03) and anti-CD163-dex (p = 0.03) groups compared with the LDD and groups. There was no difference in necrotic cell volume between groups. After 30 minutes of reperfusion, haptoglobin level were significantly higher in the anti-CD163-dex and HDD groups compared with the other groups. Alanine aminotransferase and alkaline phosphatase were significantly higher in the HDD group compared with the control group after 24 hours' reperfusion. Conclusions: We show that pharmacological preconditioning with anti-CD163-dex and HDD reduces the number of apoptotic cells following IRI compared with controls. There was no difference regarding the amount of necrosis. The present study did not allow us to conclude whether the effect of anti-CD163-dex on IRI was caused by an inhibition of the inflammatory response.