|
|
|
|
|
|
Article Detail
|
|
Label
|
|
|
Label
|
|
|
|
The Anti-apoptotic, Anti-inflammatory and Antioxidant Effects of Enoxaparin on Renal Ischemia Reperfusion Injury in Adult Male Rats
|
|
| Author:
|
NAJAH R. HADI, LAMAN MANSOUR, ABDULLAH JASIM, DINA JAMIL, HAYDER AL-AUBAIDY
|
| 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 occur, this will induce oxidative stress, inflammatory process and apoptosis.
Objectives: This research aimed to investigate the anti-apoptotic, anti-inflammatory and antioxidant effects of enoxaparin in renal ischemia reperfusion injury in rat model.
Materials & Methods: 15 adult male Wistar Albino rats were randomly divided into 3 groups (five rats in each group): Sham group underwent laparotomy incision without induction of ischemia reperfusion), Control group (Rats underwent 30 minutes bilateral renal ischemia followed by 2 hours reperfusion), Enoxaparin group (same as in control group+ 250 IU/kg enoxaparin). After 2 hrs. of reperfusion, the kidneys and blood were harvested. Blood samples were used to assess serum creatinine and urea. Renal tissues were used to assess the following markers (Bax, Bcl2, TNF-alpha, F2-isoprostane and Notch2/Hes1) as well as histological examination.
Results: Serum creatinine, serum urea, 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. Histopathological studies demonstrated severe kidney injury in the control group as compared with sham group. Kidneys of rats in enoxaparin treated group demonstrated functional and histological improvement by significant decrease in serum creatinine and urea, and renal tissue level of Bax, TNF-alpha, F2-isoprostane, Notch2/Hes1. Anti-apoptotic protein Bcl2 was significantly (p value = 0.05) increased in the enoxaparin treated group as compared with control group. The severity score of tubular injury also significantly decreased in enoxaparin treated group as compared with control group.
Conclusion: Enoxaparin significantly decreased renal ischemia reperfusion injury in rats as manifested by the significant reduction in the pro-apoptotic protein Bax, associated with the significant increase in the 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 enoxaparin treated group as compared with control group.
Abbreviations: I/R: ischemia reperfusion, RIRI: renal ischemia reperfusion injury, AKI: acute kidney injury, CKD: chronic kidney disease, ROS: reactive oxygen species, NFkB: Nuclear factor kappa-light-chain-enhancer of activated B cells, TNF-alpha: Tumor necrosis factor-alpha, Notch2/Hes1: Notch2/Hes1 receptor, Bax: BCL2 associated X protein, Bcl2: B-cell lymphoma2 protein family, R/I (renal ischemia), IHC (immunohistochemistry).
|
| Keyword:
|
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 occur, this will induce oxidative stress, inflammatory process and apoptosis. Objectives: This research aimed to investigate the anti-apoptotic, anti-inflammatory and antioxidant effects of enoxaparin in renal ischemia reperfusion injury in rat model. Materials & Methods: 15 adult male Wistar Albino rats were randomly divided into 3 groups (five rats in each group): Sham group underwent laparotomy incision without induction of ischemia reperfusion), Control group (Rats underwent 30 minutes bilateral renal ischemia followed by 2 hours reperfusion), Enoxaparin group (same as in control group+ 250 IU/kg enoxaparin). After 2 hrs. of reperfusion, the kidneys and blood were harvested. Blood samples were used to assess serum creatinine and urea. Renal tissues were used to assess the following markers (Bax, Bcl2, TNF-alpha, F2-isoprostane and Notch2/Hes1) as well as histological examination. Results: Serum creatinine, serum urea, 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. Histopathological studies demonstrated severe kidney injury in the control group as compared with sham group. Kidneys of rats in enoxaparin treated group demonstrated functional and histological improvement by significant decrease in serum creatinine and urea, and renal tissue level of Bax, TNF-alpha, F2-isoprostane, Notch2/Hes1. Anti-apoptotic protein Bcl2 was significantly (p value = 0.05) increased in the enoxaparin treated group as compared with control group. The severity score of tubular injury also significantly decreased in enoxaparin treated group as compared with control group. Conclusion: Enoxaparin significantly decreased renal ischemia reperfusion injury in rats as manifested by the significant reduction in the pro-apoptotic protein Bax, associated with the significant increase in the 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 enoxaparin treated group as compared with control group. Abbreviations: I/R: ischemia reperfusion, RIRI: renal ischemia reperfusion injury, AKI: acute kidney injury, CKD: chronic kidney disease, ROS: reactive oxygen species, NFkB: Nuclear factor kappa-light-chain-enhancer of activated B cells, TNF-alpha: Tumor necrosis factor-alpha, Notch2/Hes1: Notch2/Hes1 receptor, Bax: BCL2 associated X protein, Bcl2: B-cell lymphoma2 protein family, R/I (renal ischemia), IHC (immunohistochemistry).
|
| EOI:
|
-
|
| DOI:
|
https://doi.org/10.31838/ijpr/2021.13.01.820
|
| Download:
|
Request For Article
|
|
|
|
|
|
|
|
|
|
|