Effect of combination sildenafil and gemfibrozil on cisplatin-induced nephrotoxicity; role of heme oxygenase-1
| العنوان: | Effect of combination sildenafil and gemfibrozil on cisplatin-induced nephrotoxicity; role of heme oxygenase-1 |
|---|---|
| المؤلفون: | Ahmed Zahran, Wesam Ismail, Mahmoud A Kora, Ahmed A Rabie, Dina Sabry, Safaa Behiry |
| المصدر: | Renal Failure Renal Failure, Vol 40, Iss 1, Pp 371-378 (2018) |
| بيانات النشر: | Taylor & Francis, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Apoptosis, Pharmacology, Critical Care and Intensive Care Medicine, medicine.disease_cause, lcsh:RC870-923, Kidney, chemistry.chemical_compound, oxidative stress and sildenafil, 0302 clinical medicine, Laboratory Study, Neoplasms, Gemfibrozil, Urea, Renal Insufficiency, heme oxygenase-1, cisplatin nephrotoxicity, General Medicine, Glutathione, Acute kidney injury, medicine.anatomical_structure, Treatment Outcome, Nephrology, 030220 oncology & carcinogenesis, gemfibrozil, Creatinine, cardiovascular system, Drug Therapy, Combination, medicine.drug, Sildenafil, Antineoplastic Agents, Sildenafil Citrate, Nephrotoxicity, 03 medical and health sciences, medicine, Animals, Humans, Cisplatin, business.industry, fungi, lcsh:Diseases of the genitourinary system. Urology, respiratory tract diseases, Rats, Heme oxygenase, Disease Models, Animal, Oxidative Stress, 030104 developmental biology, chemistry, business, Oxidative stress, Biomarkers |
| الوصف: | 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. |
| اللغة: | English |
| تدمد: | 1525-6049 0886-022X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::52ab7cad530ae4b536f7a86921c69383 http://europepmc.org/articles/PMC6014327 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....52ab7cad530ae4b536f7a86921c69383 |
| قاعدة البيانات: | OpenAIRE |
PDF full text from Publisher | تدمد: | 15256049 0886022X |
|---|