Intestinal inflammatory and redox responses to the perioperative administration of teduglutide in rats

Abstract Purpose: To investigate the inflammatory and redox responses to teduglutide on an animal model of laparotomy and intestinal anastomosis. Methods: Wistar rats (n=62) were allocated into four groups: "Ileal Resection and Anastomosis" vs. "Laparotomy", each one split into "Postoperative Teduglutide Administration" vs. "No Treatment"; and euthanized at the third or the seventh day. Ileal and blood samples were recovered at the baseline and at the euthanasia. Flow cytometry was used to study the inflammatory response (IL-1α, MCP-1, TNF-α, IFN-γ and IL-4 levels), oxidative stress (cytosolic peroxides, mitochondrial reactive species, intracellular glutathione and mitochondrial membrane potential) and cellular viability and death (annexin V/propidium iodide double staining). Results: Postoperative teduglutide treatment was associated with higher cellular viability index and lower early apoptosis ratio at the seventh day; higher cytosolic peroxides level at the third day and mitochondrial overgeneration of reactive species at the seventh day; higher tissue concentration of IL-4 and lower local pro-to-anti-inflammatory cytokines ratio at the seventh day. Conclusion: Those findings suggest an intestinal pro-oxidative and anti-inflammatory influence of teduglutide on the peri-operative context with a potential interference in the intestinal anastomotic healing.

Study of hepatocellular function in the murine model following hepatic artery selective clamping

PURPOSE: To investigate the impact of selective hepatic artery clamping (SHAC) in hepatocellular function. METHODS: Three groups of Wistar male rats were subjected to SHAC ischemia period of 60min: Group A continuous SHAC were subjected to SHAC ischemia period of 60min, Group B intermittent SHAC of 30min with 5min of reperfusion and Group C intermittent SHAC of 15min with 5min of reperfusion. Animals without SHAC were included-Group D. To evaluate hepatocellular function blood markers and hepatic extraction function (HEF) using 99mTc-mebrofenin were performed before and after surgery. Flow cytometry was used to analyze oxidative stress and cell viability. RESULTS: A mortality rate of 7.6% in Group A was observed. HEF maintained normal values between the groups. Flow cytometry demonstrated no significant differences between the groups in viability, type of cell death as well as in the production of reactive oxygen species. CONCLUSIONS: The selective hepatic artery clamping compared to other clamping techniques results on increased cell viability and decreased hepatocyte death. The SHAC is a potential alternative to decrease per-operative bleeding while maintaining hepatocellular function.