|
|
|
|
|
|
Article Detail
|
|
Label
|
|
|
Label
|
|
|
|
The Anti-apoptotic, Anti-inflammatory and Anti-oxidant Effects of Ranolazine on Renal Ischemia Reperfusion Injury in Adult Male Rats
|
|
| Author:
|
, LAMAAN M.ABBAS, AHMED M.ABDUL HAMEED, WEAAM J.ABBAS, MAYS ABDULSATAR, NAJAH R.HADI
|
| Abstract:
|
Background: Renal ischemia and reperfusion is the main cause of acute injury of the kidney and associated with increase morbidity, mortality, and long stage hospitalization. Renal ischemia and reperfusion occurs in approximately 10 -20% of kidney transplant recipients. If ischemia and reperfusion occurs, this will induce oxidative stress, inflammatory process and apoptosis. Objectives: This research aimed to investigate the anti-apoptotic, anti-inflammatory and anti-oxidant effects of ranolazine in renal ischemia reperfusion injury in rat model. Materials & Methods: 24 adult male Wistar Albino rats were divided randomly into 4 groups (six rats in each group): Sham group underwent laparotomy without induction of ischemia reperfusion, Control group (Rats underwent 30 minutes bilateral renal ischemia followed by 2 hours reperfusion), Vehicle group (same as in control group+ DMSO), and Ranolazine group (same as in control group+ 30mg/kg ranolazine). After 2 hrs of reperfusion, the kidney and blood were harvested. Blood sample was used to assess serum creatinine and blood urea nitrogen (S.cr &BUN). Renal tissue was used to assess Bax, Bcl2, TNF-alpha, F2-isoprostane and Notch2/Hes1 as well as histological examination. Results: At the end of experiment, S.cr. BUN, and renal tissue level of Bax, TNF-alpha, F2-isoprostane, Notch2/Hes1, were significantly increased in control group as compared with sham group. There was also a significant decrease in the level of anti-apoptotic protein Bcl2 in the control group as compared with sham group. Histopathology study demonstrated severe kidney injury in the control group as compared with sham group. Kidneys of rats in ranolazine treated group demonstrated functional and histological improvement by significant decrease in S.cr. BUN, and renal tissue level of Bax, TNF-alpha, F2-isoprostane, Notch2/Hes1.Anti apoptotic protein Bcl2 was significantly (p value = 0.01) higher level in ranolazine treated group as compared with control and vehicle groups. The severity score of tubular injury also significantly decreased in ranolazine treated group as compared with control and vehicle groups. Conclusion: From the overall results, ranolazine significantly decreases renal ischemia reperfusion injury in rats which was achieved by significantly decrease pro-apoptotic protein Bax, and increase anti apoptotic protein Bcl2. The inflammatory marker TNF-alpha, and oxidative stress marker F2-isoprostane, Notch2/Hes1 signaling pathway were significantly decreased and down regulated in ranolazine treated group as compared with control and vehicle groups.
|
| Keyword:
|
Ranolazine, Ischemia reperfusion injury, Bax, Bcl2, TNF-alpha, F2-isoprostane, Notch2/Hes1.
|
| EOI:
|
-
|
| DOI:
|
https://doi.org/10.31838/ijpr/2021.13.01.658
|
| Download:
|
Request For Article
|
|
|
|
|
|
|
|
|
|
|