Effect of combination sildenafil and gemfibrozil on cisplatin-induced nephrotoxicity; role of heme oxygenase-1
Background/aim: Cisplatin-induced nephrotoxicity in large proportion of patients. The aim of this work is to clarify the effect of combination of sildenafil and gemfibrozil on cisplatin-induced nephrotoxicity either before or after cisplatin treatment and determination of nephrotoxicity predictors a...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2018-10-01
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| Series: | Renal Failure |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/0886022X.2018.1455596 |
| _version_ | 1818408697200640000 |
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| author | Safaa Behiry Ahmed Rabie Mahmoud Kora Wesam Ismail Dina Sabry Ahmed Zahran |
| author_facet | Safaa Behiry Ahmed Rabie Mahmoud Kora Wesam Ismail Dina Sabry Ahmed Zahran |
| author_sort | Safaa Behiry |
| collection | DOAJ |
| description | Background/aim: Cisplatin-induced nephrotoxicity in large proportion of patients. The aim of this work is to clarify the effect of combination of sildenafil and gemfibrozil on cisplatin-induced nephrotoxicity either before or after cisplatin treatment and determination of nephrotoxicity predictors among the measured tissue markers. Methods: Thirty two adult male albino rats were divided into four equal groups (G) GI control, GII received cisplatin, GIII received sildenafil and gemfibrozil before cisplatin, GIV received sildenafil and gemfibrozil after cisplatin. Creatinine and urea were measured and animals were sacrificed and kidney was taken for histopathology. The following tissue markers were measured, heme oxygenase-1 (HO-1) activity, reduced glutathione, quantitative (real-time polymerase chain reaction) RT-PCR for gene expression of tumor necrosis factor alpha (TNF-α) and endothelial nitric oxide synthase (ENOS) level. Results: GII developed AKI demonstrated by significantly high urea and creatinine and severe diffuse (80–90%) tubular necrosis. TNF-α was highly and significantly elevated while the rest of tissue markers were significantly reduced in GI1 compared to other groups. GIV showed better results compared to GIII. There was a significant positive correlation between creatinine and TNF-α when combining GI and GII while there were significant negative correlation between creatinine and other tissue markers in same groups. Linear regression analysis demonstrated that HO-1 was the independent predictor of AKI demonstrated by elevated creatinine among GI and GII. Conclusions: Combination of sildenafil and gemfibrozil can be used in treatment of cisplatin-induced nephrotoxicity. HO-1 is a promising target for prevention and/or treatment of cisplatin-induced nephrotoxicity. |
| first_indexed | 2024-12-14T09:47:51Z |
| format | Article |
| id | doaj.art-1e33fdd174104f869899d5cae38bcf17 |
| institution | Directory Open Access Journal |
| issn | 0886-022X 1525-6049 |
| language | English |
| last_indexed | 2024-12-14T09:47:51Z |
| publishDate | 2018-10-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Renal Failure |
| spelling | doaj.art-1e33fdd174104f869899d5cae38bcf172022-12-21T23:07:35ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492018-10-0140137137810.1080/0886022X.2018.14555961455596Effect of combination sildenafil and gemfibrozil on cisplatin-induced nephrotoxicity; role of heme oxygenase-1Safaa Behiry0Ahmed Rabie1Mahmoud Kora2Wesam Ismail3Dina Sabry4Ahmed Zahran5Cairo UniversityMenoufia UniversityMenoufia UniversityBeni Suef UniversityCairo UniversityMenoufia UniversityBackground/aim: Cisplatin-induced nephrotoxicity in large proportion of patients. The aim of this work is to clarify the effect of combination of sildenafil and gemfibrozil on cisplatin-induced nephrotoxicity either before or after cisplatin treatment and determination of nephrotoxicity predictors among the measured tissue markers. Methods: Thirty two adult male albino rats were divided into four equal groups (G) GI control, GII received cisplatin, GIII received sildenafil and gemfibrozil before cisplatin, GIV received sildenafil and gemfibrozil after cisplatin. Creatinine and urea were measured and animals were sacrificed and kidney was taken for histopathology. The following tissue markers were measured, heme oxygenase-1 (HO-1) activity, reduced glutathione, quantitative (real-time polymerase chain reaction) RT-PCR for gene expression of tumor necrosis factor alpha (TNF-α) and endothelial nitric oxide synthase (ENOS) level. Results: GII developed AKI demonstrated by significantly high urea and creatinine and severe diffuse (80–90%) tubular necrosis. TNF-α was highly and significantly elevated while the rest of tissue markers were significantly reduced in GI1 compared to other groups. GIV showed better results compared to GIII. There was a significant positive correlation between creatinine and TNF-α when combining GI and GII while there were significant negative correlation between creatinine and other tissue markers in same groups. Linear regression analysis demonstrated that HO-1 was the independent predictor of AKI demonstrated by elevated creatinine among GI and GII. Conclusions: Combination of sildenafil and gemfibrozil can be used in treatment of cisplatin-induced nephrotoxicity. HO-1 is a promising target for prevention and/or treatment of cisplatin-induced nephrotoxicity.http://dx.doi.org/10.1080/0886022X.2018.1455596Acute kidney injurycisplatin nephrotoxicitygemfibrozilheme oxygenase-1oxidative stress and sildenafil |
| spellingShingle | Safaa Behiry Ahmed Rabie Mahmoud Kora Wesam Ismail Dina Sabry Ahmed Zahran Effect of combination sildenafil and gemfibrozil on cisplatin-induced nephrotoxicity; role of heme oxygenase-1 Renal Failure Acute kidney injury cisplatin nephrotoxicity gemfibrozil heme oxygenase-1 oxidative stress and sildenafil |
| title | Effect of combination sildenafil and gemfibrozil on cisplatin-induced nephrotoxicity; role of heme oxygenase-1 |
| title_full | Effect of combination sildenafil and gemfibrozil on cisplatin-induced nephrotoxicity; role of heme oxygenase-1 |
| title_fullStr | Effect of combination sildenafil and gemfibrozil on cisplatin-induced nephrotoxicity; role of heme oxygenase-1 |
| title_full_unstemmed | Effect of combination sildenafil and gemfibrozil on cisplatin-induced nephrotoxicity; role of heme oxygenase-1 |
| title_short | Effect of combination sildenafil and gemfibrozil on cisplatin-induced nephrotoxicity; role of heme oxygenase-1 |
| title_sort | effect of combination sildenafil and gemfibrozil on cisplatin induced nephrotoxicity role of heme oxygenase 1 |
| topic | Acute kidney injury cisplatin nephrotoxicity gemfibrozil heme oxygenase-1 oxidative stress and sildenafil |
| url | http://dx.doi.org/10.1080/0886022X.2018.1455596 |
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