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Potential Nephroprotective Effect of Valsartan in Renal Ischemia Reperfusion Injury Role of NF-KBP65 Pathway in Rat
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| Author:
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BASIM MOHAMMAD, MAYSAA ALI ABDUL KAHALEQ, MUNTHER ABOSAOODA, ALAA K. MOSA, MOHAMMED A. ABDULHUSSEIN, NAJAH R. HADI
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| Abstract:
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Acute kidney injury (AKI) with all advances in nursing measures and therapeutic strategies, such as kidney transplantation and dialysis, mortality rate of patients with AKI is very high in past 30 years. Despite the pathophysiology of IRI is not totally understood, several critical mechanisms cause reversal of kidney damage have been demonstrated. In ischemic kidney and successive of generation of reactive oxygen species (ROS), re-oxygenation at reperfusion phase activate a cascade of destroying cellular responses causing to cell death, inflammation, and acute kidney failure. Valsartan is an Angotensin2 receptor blocker which is used as antihypertensive drug. It demonstrates organ protective effects in hypertension, attenuated renal injury possibly through its anti-inflammatory and antioxidant effects and it offer kidney protection as evidence by significant reduction in kidney injury score.
Objective: To study the potential Nephroprotective effect of Valsartan in RIRI
Materials & methods: After one week of acclimatization, the rat was randomly classified into four groups (6 rat in each) as follows:
1-IRI (control) group: rats subjected to the renal ischemia for 30 min by clamping renal artery and reperfusion for 2 hour.
2-sham group: rats underwent the same anesthetic and surgical procedure except clamping of bilateral renal artery.
3-control vehicle group: rats received 10 % dimethyl sulfoxide by I.P route and underwent renal ischemia for 30 min by clamping of renal artery and then 2hour reperfusion.
4-Valsartan treated group: rats pretreated with Valsartan 10 mg/kg I.P, 30 min before clamping of renal artery and then underwent renal ischemia for 30 min and then reperfusion for 2 hour. At the end of reperfusion time renal tissue and blood samples were collected. Blood samples used for measurement of IL1ß, NF-KB p65, TLR4, NGAL and urea and creatinine for measurement of renal function. Renal tissue used for determination of histopathological changes.
Results: Renal IRI causes significant (p=0.05) increase in tissue level of IL-1ß, NGAL, TLR-4 and NF-KB p65 and serum urea, creatinine, pretreatment with Valsartan cause significant (p =0.05) decrease in tissue level of IL-1ß, NF-KB p65, TLR-4, NGAL and serum urea, creatinine, also cause significant reversal of tissue damage when compared with IRI group.
Conclusion: Pretreatment with Valsartan significantly decreases renal ischemia reperfusion injury in the rat via their pleiotropic effects as anti-oxidant, anti-inflammatory and anti- apoptotic activity
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| Keyword:
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(RIRI), Valsartan
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| EOI:
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| DOI:
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https://doi.org/10.31838/ijpr/2020.12.01.176
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| Download:
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