Beneficial Effects of Short-Term Calorie Restriction against Cisplatin-Induced Acute Renal Injury in Aged Rats

Background: The therapeutic use of the antineoplastic drug cisplatin (DDP) in the elderly is limited by its nephrotoxic effects. The aim of this study was to examine the effect of short-term calorie restriction (CR) on DDP-induced nephrotoxicity in aged rats. Methods: A group of 25-month-old male Sprague-Dawley rats were divided into two groups: ad libitum (AL) and CR, which were fed 60% of the food consumed by AL rats for 8 weeks. The two groups were each further randomly divided into two subgroups: OAL control, OAL+DDP, OCR control, and OCR+DDP. A single dose of DDP ( 6 mg/kg) was injected intraperitoneally. Functional and structural changes of the kidneys were evaluated quantitatively by biochemical, histopathological, and morphometric analyses. Results: At the end of the 8 weeks, rats in the OCR group lost 14.8% more body mass than rats in the OAL group. Pretreatment with CR had several effects: ( 1) it reduced the levels of blood urea nitrogen and serum creatinine, ( 2) it reduced the magnitude of the renal tubular epithelial damage, and ( 3) it significantly reduced the incidence of activated caspase-3 and TUNEL-positive cells in kidneys injured by DDP. However, SIRT1 had the opposite trend after DDP application between the two groups. Conclusions: Short-term CR exhibits a renoprotective effect in experimental DDP-induced renal injury, the mechanism of which may involve CR antiapoptotic effects and promotion of SIRT1. (c) 2014 S. Karger AG, Basel