ABSTRACT
BACKGROUND AND AIMS: If temporary inflow occlusion is required during liver resection, the postoperative course might be complicated by ischaemia-reperfusion injury. Steroids protect against ischaemia-reperfusion injury; however, due to its anti-proliferative character concerns exist on its use on liver regeneration after resection. We investigated the effects of methylprednisolone on hepatocyte proliferation after partial hepatectomy with temporary inflow occlusion. PATIENTS AND METHODS: Prior to surgery, one group of Wistar rats received methylprednisolone, while a second group served as non-treated controls. Ischaemia-reperfusion injury was indicated by AST, ALT, and GLDH at 6 h after surgery. Immunohistochemistry tools were used to determine the mitotic index and Ki-67 expression, while cyclin D1 expression characterized the proliferative activity on days 1, 4, 7, and 10. RESULTS: The post-ischaemic liver enzyme release had significantly decreased in the methylprednisolone group, while expression of cyclin D1, percentage of Ki-67-positive cells, and mitotic cell index were comparable in both groups. Similar results were found for bilirubin and albumin and for weight of proliferating liver. CONCLUSION: Although steroid administration significantly reduced ischaemia-reperfusion-associated tissue injury, it has no apparent effects on hepatic regeneration. Thus, steroids could be recommended if a temporary liver ischaemia is required during surgery, in order to reduce complications caused by severe ischaemia-related organ dysfunction.
Subject(s)
Anti-Inflammatory Agents/administration & dosage , Cyclin D1/analysis , Hepatectomy , Ki-67 Antigen/analysis , Liver Regeneration , Methylprednisolone/administration & dosage , Reperfusion Injury/prevention & control , Animals , Blotting, Western , Data Interpretation, Statistical , Immunohistochemistry , Injections, Intravenous , Male , Postoperative Period , Preoperative Care , Rats , Rats, Wistar , Time FactorsABSTRACT
BACKGROUND: Ischemic preconditioning (I/P) and methylprednisolone (MP) have been suggested to protect against ischemia-reperfusion (IR) injury, which results in an increased tolerance against organ hypoxia. METHODS: Before 45 minutes of hepatic ischemia, male Wistar rats were pretreated with either I/P (5/30 minutes) or MP (30 mg/kg BW). The degree of IR injury and the postischemic inflammatory (leukocyte infiltration, myeloperoxidase, intercellular adhesion molecule-1) and apoptotic (TUNEL, caspase 3, cytochrome C) activity was measured in both groups and compared with non-pretreated (ischemic) animals. RESULTS: Histology and enzyme release revealed that I/P and MP treatment provided significant protection as compared with ischemic controls. TUNEL-positive cells, as well as caspase 3 and cytochrome C expression, were clearly reduced in hepatic tissue of MP-treated animals and partially reduced in I/P-treated animals when compared with ischemic animals. The inflammatory response was considerably reduced in MP- and I/P-treated animals, especially in the early period after ischemia. NF-kappaB/Rel-binding activity was increased after I/P and decreased in MP-treated animals, whereas ischemic controls showed a constant binding activity. CONCLUSIONS: MP (probably by downregulation of NF-kappaB-binding activity) and I/P attenuated the postischemic apoptotic and inflammatory response. Both treatments equally reduced IR-related hepatocellular damage, and, thus, may also be applied equally in surgery involving warm organ hypoxia.