Short-Term Diet Restriction but Not Alternate Day Fasting Prevents Cisplatin-Induced Nephrotoxicity in Mice
Cisplatin (CP) is one of the most preferred platinum-containing antineoplastic drugs. However, even in nontoxic plasma concentrations, it may cause kidney injury. To be able to increase its effective pharmacological dose, its side effects need to be regarded. Diet restriction (DR) has been demonstra...
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MDPI AG
2020-02-01
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| Online Access: | https://www.mdpi.com/2227-9059/8/2/23 |
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| author | Evrin Gunebakan Esra Yalcin Esra Cikler Dulger Ahmet Yigitbasi Nilay Ates Aysun Caglayan Mustafa C. Beker Kazim Sahin Hasan Korkaya Ertugrul Kilic |
| author_facet | Evrin Gunebakan Esra Yalcin Esra Cikler Dulger Ahmet Yigitbasi Nilay Ates Aysun Caglayan Mustafa C. Beker Kazim Sahin Hasan Korkaya Ertugrul Kilic |
| author_sort | Evrin Gunebakan |
| collection | DOAJ |
| description | Cisplatin (CP) is one of the most preferred platinum-containing antineoplastic drugs. However, even in nontoxic plasma concentrations, it may cause kidney injury. To be able to increase its effective pharmacological dose, its side effects need to be regarded. Diet restriction (DR) has been demonstrated to improve cellular survival in a number of disorders. In this context, we investigated the role of DR in CP-induced nephrotoxicity (CPN). Besides alternate DR, animals were exposed to DR for 3 days prior or after CP treatment. Here, we observed that both 3 days of DR reverses the nephrotoxic effect of CP, which was associated with improved physiological outcomes, such as serum creatine, blood-urea nitrogen and urea. These treatments significantly increased phosphorylation of survival kinases PI3K/Akt and ERK-1/2 and decreased the level of stress kinase JNK were noted. In addition, the activation level of signal transduction mediator p38 MAPK phosphorylation was higher particularly in both three-day DR groups. Next, animals were fed with carbohydrate-, protein- or fat-enriched diets in the presence of CP. Results indicated that not only fasting but also dietary content itself may play a determinant role in the severity of CPN. Our data suggest that DR is a promising approach to reduce CPN by regulating metabolism and cell signaling pathways. |
| first_indexed | 2024-12-13T01:54:36Z |
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| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-12-13T01:54:36Z |
| publishDate | 2020-02-01 |
| publisher | MDPI AG |
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| series | Biomedicines |
| spelling | doaj.art-ccbe71fbf0bc4b2db1e7ed9d281577922022-12-22T00:03:26ZengMDPI AGBiomedicines2227-90592020-02-01822310.3390/biomedicines8020023biomedicines8020023Short-Term Diet Restriction but Not Alternate Day Fasting Prevents Cisplatin-Induced Nephrotoxicity in MiceEvrin Gunebakan0Esra Yalcin1Esra Cikler Dulger2Ahmet Yigitbasi3Nilay Ates4Aysun Caglayan5Mustafa C. Beker6Kazim Sahin7Hasan Korkaya8Ertugrul Kilic9Department of Physiology, School of Medicine, Istanbul Medipol University, Istanbul 34810, TurkeyDepartment of Physiology, School of Medicine, Istanbul Medipol University, Istanbul 34810, TurkeyDepartment of Histology and Embryology, Hamidiye Medical School, University of Health Sciences, Istanbul 34668, TurkeyDepartment of Internal Medicine, School of Medicine, Trakya University, Edirne 22030, TurkeyDepartment of Pharmacology, School of Medicine, Istanbul Medipol University, Istanbul 34810, TurkeyDepartment of Physiology, School of Medicine, Istanbul Medipol University, Istanbul 34810, TurkeyDepartment of Physiology, School of Medicine, Istanbul Medipol University, Istanbul 34810, TurkeyAnimal Nutrition Department, School of Veterinary Medicine, Firat University, Elazig 23119, TurkeyDepartment of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USADepartment of Physiology, School of Medicine, Istanbul Medipol University, Istanbul 34810, TurkeyCisplatin (CP) is one of the most preferred platinum-containing antineoplastic drugs. However, even in nontoxic plasma concentrations, it may cause kidney injury. To be able to increase its effective pharmacological dose, its side effects need to be regarded. Diet restriction (DR) has been demonstrated to improve cellular survival in a number of disorders. In this context, we investigated the role of DR in CP-induced nephrotoxicity (CPN). Besides alternate DR, animals were exposed to DR for 3 days prior or after CP treatment. Here, we observed that both 3 days of DR reverses the nephrotoxic effect of CP, which was associated with improved physiological outcomes, such as serum creatine, blood-urea nitrogen and urea. These treatments significantly increased phosphorylation of survival kinases PI3K/Akt and ERK-1/2 and decreased the level of stress kinase JNK were noted. In addition, the activation level of signal transduction mediator p38 MAPK phosphorylation was higher particularly in both three-day DR groups. Next, animals were fed with carbohydrate-, protein- or fat-enriched diets in the presence of CP. Results indicated that not only fasting but also dietary content itself may play a determinant role in the severity of CPN. Our data suggest that DR is a promising approach to reduce CPN by regulating metabolism and cell signaling pathways.https://www.mdpi.com/2227-9059/8/2/23cisplatinfastingrenal protectionacute kidney injurynephrotoxicitymapk pathway |
| spellingShingle | Evrin Gunebakan Esra Yalcin Esra Cikler Dulger Ahmet Yigitbasi Nilay Ates Aysun Caglayan Mustafa C. Beker Kazim Sahin Hasan Korkaya Ertugrul Kilic Short-Term Diet Restriction but Not Alternate Day Fasting Prevents Cisplatin-Induced Nephrotoxicity in Mice Biomedicines cisplatin fasting renal protection acute kidney injury nephrotoxicity mapk pathway |
| title | Short-Term Diet Restriction but Not Alternate Day Fasting Prevents Cisplatin-Induced Nephrotoxicity in Mice |
| title_full | Short-Term Diet Restriction but Not Alternate Day Fasting Prevents Cisplatin-Induced Nephrotoxicity in Mice |
| title_fullStr | Short-Term Diet Restriction but Not Alternate Day Fasting Prevents Cisplatin-Induced Nephrotoxicity in Mice |
| title_full_unstemmed | Short-Term Diet Restriction but Not Alternate Day Fasting Prevents Cisplatin-Induced Nephrotoxicity in Mice |
| title_short | Short-Term Diet Restriction but Not Alternate Day Fasting Prevents Cisplatin-Induced Nephrotoxicity in Mice |
| title_sort | short term diet restriction but not alternate day fasting prevents cisplatin induced nephrotoxicity in mice |
| topic | cisplatin fasting renal protection acute kidney injury nephrotoxicity mapk pathway |
| url | https://www.mdpi.com/2227-9059/8/2/23 |
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