Short-Term Diet Restriction but Not Alternate Day Fasting Prevents Cisplatin-Induced Nephrotoxicity in Mice

Biomedicines

Kazim Sahin¹  Hasan Korkaya²  Esra Cikler Dulger³  Ahmet Yigitbasi⁴  Nilay Ates⁵  Ertugrul Kilic⁶  Aysun Caglayan⁶  Esra Yalcin⁶  Evrin Gunebakan⁶  MustafaC. Beker⁶ 

[1] Animal Nutrition Department, School of Veterinary Medicine, Firat University, Elazig 23119, Turkey;Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA;Department of Histology and Embryology, Hamidiye Medical School, University of Health Sciences, Istanbul 34668, Turkey;Department of Internal Medicine, School of Medicine, Trakya University, Edirne 22030, Turkey;Department of Pharmacology, School of Medicine, Istanbul Medipol University, Istanbul 34810, Turkey;Department of Physiology, School of Medicine, Istanbul Medipol University, Istanbul 34810, Turkey;

关键词: cisplatin;    fasting;    renal protection;    acute kidney injury;    nephrotoxicity;    mapk pathway;   

DOI  :  10.3390/biomedicines8020023

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown