The Anti-Apoptotic, Anti-Inflammatory And Anti-Oxidant Effects Of Olmesartan On Renal I / R Injury In Male Rat Model

Abstract

Ahmed M. Abdul Hameed, Murooj L. Altemimi, Rihab H. Al-Mudhafar, Dhefaf H. Al-Mudhafar, Najah R. Hadi

Background: Ischemia reperfusion injury (IRI) is considered the main important factor that determined the morbidity and mortality in many disorders as example acute kidney injury (AKI), myocardial infarction (MI), ischemic stroke and sepsis. In certain situations as major surgery and organ transplantation, IRI is considered the main challenge that affected on healing and clinical outcomes. During ischemia, there is reduction in blood supply to ischemic organ and this will lead to poorly supply of oxygen (hypoxia) and nutrients and decrease the discharge of metabolic waste products and so will lead to accumulate carbon dioxide (CO2) and other debris. Severe ischemia and hypoxia for long time lead to micro-vascular changing in structure and dysfunction. When the ischemic tissue is reperfused by rapidly new blood that rich in oxygen and nutrient this will lead to micro vascular injury that is occur due to increase vascular permeability and leakage of fluid and protein from the capillaries to tissues lead to edema and damage. Also when the rapidly reperfusion occurred by highly oxygenated and nutrient blood to ischemic or damaging tissues lead to releasing of reactive oxygen species (ROS) from endothelial layer of capillaries and potentiate the inflammatory process and releasing of inflammatory mediators and factors such as tumor necrosis factor alpha (TNF-α), interferon gamma, interleukin 6 (IL-6), and interleukin-1β (IL-1β)and also releasing matrix metalloproteinase 9 enzyme (MMP9), complement protein and inflammatory or immunity cells as Neutrophil, macrophage, lymphocyte and others. Objective: This experimental research is done to investigate the possible Nephroprotective effect of Olmesartanon bilateral renal I/R injury in male rats through determining several renal function biomarkers as U & C, several inflammatory mediators as TNFα and MMP-9, antioxidant markers as TAC, several apoptotic markers as BCL-2 and BAX and also through histopathology scores. Materials and Method: In this study, 20 adult Wister Albino rats were used with 20-24 weeks in age and weighing 200-350 g. The adult rats were divided randomly into equal 4 groups (5 rats in each group) as the following:
1. Sham group: All 5 rats underwent the same anesthetic and surgical procedures for an identical period of time for ischemia and reperfusion without ischemia reperfusion induction. Renal tissues and blood samples were collected.
2. Control group: All 5 rats underwent median laparotomy under anesthesia, followed by 30min bilateral renal ischemia, and then renal tissues and blood samples were collected after 2h of reperfusion.
3. Vehicle group: All 5 rats pretreated with intraperitoneally injection of DMSO 30 min before ischemia reperfusion injury and undergo bilateral renal ischemia for 30 min and reperfusion for 2 hours.
4. Olmesartan treated group: All 5 rats were pretreated with by intraperitoneally injection of Olmesartan 10 mg/kg 30 min before ischemia reperfusion injury and undergo bilateral renal ischemia for 30 min and reperfusion for 2 hours.
Results: At the end of this experimental study, we showed that the serum level of U & C and tissue level of TNFα, MMP-9and BAX in sham group are significantly lowered than those in control and vehicle groups, also we showed that the serum level of U & C and tissue level of TNFα, MMP-9and BAX in OLM group is significantly lowered than those of control and vehicle groups. On the other hand, we showed that the tissue level of TAC and Bcl-2 in sham group are significantly higher than those in both control and vehicle groups. Also we showed that the tissue level of TAC and Bcl-2 in OLM group is significantly higher than those of both control and vehicle groups. In histopathology examination, we revealed that the OLM can significantly reduce the kidney injury and minimize the severity of tubular damage and deterioration in comparison with control and vehicle groups that are showed seve