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Original Article
Egyptian Journal of Basic and Clinical Pharmacology
Vol. 7 (2017), Issue 2, pp. 25-36
doi:10.32527/2017/101423

Nicorandil Mitigates Renal Oxidative Damage, Apoptotic, and Fibrotic Changes Induced by Cyclosporine-A in Rats

Heba M. Hafez1, Mervat Z. Mohamed1, Hend Abdel-Ghany2, Nagwa M. Zenhom2, Manal A. Khalaf3, and Maram Elhussieny3

1Department of Pharmacology, Faculty of Medicine, Minia University, 61511 Minia, Egypt

2Department of Biochemistry, Faculty of Medicine, Minia University, 61511 Minia, Egypt.

3Department of Pathology, Faculty of Medicine, Minia University, 61511 Minia, Egypt.

Copyright © 2017 Heba M. Hafez et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Cyclosporine A (CsA) is one of the immunosuppressive drugs broadly used in transplantation rejection. However, nephrotoxicity arising from its long-term use constrained its efficacy. This study investigated the advantageous role of nicorandil against CsA nephrotoxicity in rats. Rats were assigned into 5 groups (n= 6 each): control group, nicorandil group, CsA group, CsA+nicorandil group, CsA+nicorandil+glibenclamide group. CsA induced Nephrotoxicity orally for 21 days. The results exhibited that CsA nephrotoxicity manifested by increasing serum urea, creatinine, and uric acid in the orchestra with histopathological changes. There was a significant rise in oxidative damage parameters;malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) without relevant effect on nitric oxide (NO) level. CsA increased the expression of transforming growth factor beta (TGF-β) and collagen 1A1 by reverse transcriptase (RT-PCR) method with reduction of immunohistochemical expression of the Bcl2 level and increasing caspase-3 level. Administration of nicorandil significantly amelioratedoxidative changes with elevation in NO level. Nicorandil prevented the elevated serum markers associated with significant improvement in TGF-β, collagen IA1 and endothelial nitric oxide synthase (eNOS) expression. Besides,immunohistochemical expression of Bcl2 significantly augmented with a reduction in caspase-3 in comparison with CsA. Glibenclamidedid not significantly have a role when combined with CsA and nicorandil. The renal protective effect of nicorandil was thought to be in part through anti-oxidant, anti-fibrotic, and antiapoptotic mechanisms. These results may offer additional nephroprotective mechanisms for nicorandil independent on its vasodilator effect.

Original Article
Egyptian Journal of Basic and Clinical Pharmacology
Vol. 7 (2017), Issue 2, pp. 25-36
doi:10.32527/2017/101423

Nicorandil Mitigates Renal Oxidative Damage, Apoptotic, and Fibrotic Changes Induced by Cyclosporine-A in Rats

Heba M. Hafez1, Mervat Z. Mohamed1, Hend Abdel-Ghany2, Nagwa M. Zenhom2, Manal A. Khalaf3, and Maram Elhussieny3

1Department of Pharmacology, Faculty of Medicine, Minia University, 61511 Minia, Egypt

2Department of Biochemistry, Faculty of Medicine, Minia University, 61511 Minia, Egypt.

3Department of Pathology, Faculty of Medicine, Minia University, 61511 Minia, Egypt.

Copyright © 2017 Heba M. Hafez et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Cyclosporine A (CsA) is one of the immunosuppressive drugs broadly used in transplantation rejection. However, nephrotoxicity arising from its long-term use constrained its efficacy. This study investigated the advantageous role of nicorandil against CsA nephrotoxicity in rats. Rats were assigned into 5 groups (n= 6 each): control group, nicorandil group, CsA group, CsA+nicorandil group, CsA+nicorandil+glibenclamide group. CsA induced Nephrotoxicity orally for 21 days. The results exhibited that CsA nephrotoxicity manifested by increasing serum urea, creatinine, and uric acid in the orchestra with histopathological changes. There was a significant rise in oxidative damage parameters;malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) without relevant effect on nitric oxide (NO) level. CsA increased the expression of transforming growth factor beta (TGF-β) and collagen 1A1 by reverse transcriptase (RT-PCR) method with reduction of immunohistochemical expression of the Bcl2 level and increasing caspase-3 level. Administration of nicorandil significantly amelioratedoxidative changes with elevation in NO level. Nicorandil prevented the elevated serum markers associated with significant improvement in TGF-β, collagen IA1 and endothelial nitric oxide synthase (eNOS) expression. Besides,immunohistochemical expression of Bcl2 significantly augmented with a reduction in caspase-3 in comparison with CsA. Glibenclamidedid not significantly have a role when combined with CsA and nicorandil. The renal protective effect of nicorandil was thought to be in part through anti-oxidant, anti-fibrotic, and antiapoptotic mechanisms. These results may offer additional nephroprotective mechanisms for nicorandil independent on its vasodilator effect.

Original Article
Egyptian Journal of Basic and Clinical Pharmacology
Vol. 7 (2017), Issue 2, pp. 25-36
doi:10.32527/2017/101423

Nicorandil Mitigates Renal Oxidative Damage, Apoptotic, and Fibrotic Changes Induced by Cyclosporine-A in Rats

Heba M. Hafez1, Mervat Z. Mohamed1, Hend Abdel-Ghany2, Nagwa M. Zenhom2, Manal A. Khalaf3, and Maram Elhussieny3

1Department of Pharmacology, Faculty of Medicine, Minia University, 61511 Minia, Egypt

2Department of Biochemistry, Faculty of Medicine, Minia University, 61511 Minia, Egypt.

3Department of Pathology, Faculty of Medicine, Minia University, 61511 Minia, Egypt.

Copyright © 2017 Heba M. Hafez et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

How to Cite this Article

Heba M. Hafez, Mervat Z. Mohamed, Hend Abdel-Ghany, Nagwa M. Zenhom, Manal A. Khalaf, and Maram Elhussieny, “Nicorandil Mitigates Renal Oxidative Damage, Apoptotic, and Fibrotic Changes Induced by Cyclosporine-A in Rats,” Egyptian Journal of Basic and Clinical Pharmacology, Vol. 7, Issue 2, pp. 25-36, 2017. doi:10.32527/2017/101423