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Nephroprotective Effect of Octreotide and Liraglutide in Renal Ischemia Reperfusion Injury in Mice
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| Author:
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ZAHRAA SALEEM, MAYSAA ALI ABDUL KAHALEQ, MUNTHER ABOSAAODA, NAJAH R. HADI, NASSER GHALY YOUSIF
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| Abstract:
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Renal ischemia reperfusion injury is a pathological event that can lead to acute renal failure (ARF), and found that 45% of the cases of ARF in the intensive care unit due to IRI in one study. It is also a common cause of graft failure after kidney transplant and increase both morbidity and early loss of transplanted kidney. Several previous studies had been reported that the underlying path physiological mechanisms of acute kidney IR injury are largely due to the generation of oxidative stress and reactive oxygen species (ROS), intense inflammatory response, and enhancement of cellular apoptosis after prolonged or even transient IR injury. Experimental studies had been demonstrated that prevention of inflammatory reaction and inhibition of the production of pro-inflammatory cytokines and oxidative stress using immunological or pharmacological therapy significantly provide protection against ischemic acute kidney injury. Mice were divided randomly into five groups (6 mice in each group): sham group: mice were underwent anesthetic and surgical procedures the same as that in ischemia group except the induction of ischemia, ischemia reperfusion group (control group): mice were underwent 30 minutes bilateral renal ischemia by clamping of right and left renal arteries and 2 hours reperfusion, vehicle group: IRI + normal saline (for both drugs) by intraperitoneal injection, 30minutes before the induction of ischemia and underwent bilateral renal ischemia for 30 minutes followed by 2 hours reperfusion, octreotide treated group: treated with a dose of octreotide (30µg/kg) by intraperitoneal injection, 30 minutes before ischemia and underwent 730 minutes bilateral renal ischemia followed by 2 hours reperfusion, Liraglutide treated group: treated with a dose of Liraglutide (1mg/kg) by intraperitoneal injection, 30min before ischemia and underwent 30 minutes bilateral renal ischemia followed by 2 hours reperfusion. At the end of the research, we observed that mean serum and kidney tissue levels of MCP-1, IL-1ß, P2X7 and renal function indices (blood urea and serum creatinine) were significantly increased in I/R (control) group in compare with sham group (P<0.05). All mice in the control group showed a significant (P<0.05) renal injury and increase in renal histology score. Both of Liraglutide and Octreotide drugs cause significant lowering of serum and tissue levels of MCP-1, IL-1ß, P2X7 in addition to cause significant reduction in renal function indices (blood urea and serum creatinine) (P<0.05). Histological found that both of drugs markedly decreased the renal injury in ischemia reperfusion injury (P<0.05). We concluded that both of octreotide and Liraglutide have a protective effect in renal I/R injury in male mice via their effects mainly as anti-inflammatory and anti-oxidant effects. Renal ischemia/ reperfusion injury (IRI), is a harmful event that result in acute kidney injury (AKI) [1]. Ischemic injury happens when there is impairment of blood flow to the tissues of the kidney, nevertheless it increase in severity when the blood flow is restored on reperfusion [2]. Also there is either localized or generalized impairment in the delivery of oxygen(O2) and nutrients to tissues of the kidney, accumulation of cell waste product [3]. There is unevenness of local tissue o2 supply and demand and the aggregation of waste products of anabolism and catabolism.
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| Keyword:
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Octreotide, Liraglutide, RIR
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| EOI:
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| DOI:
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https://doi.org/10.31838/ijpr/2020.12.01.177
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