Abstract
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.
Journal Section:
Original Paper
References
1.
Muggia FM: Cisplatin update. Semin Oncol 1991;18:1-4.
2.
Gadducci A, Brunetti I, Bruzzone M, Carnino F, Chiara S, Conte PF, Fioretti P, Foglia G, Ragni N: Cisplatin-based combination chemotherapy with or without doxorubicin in advanced epithelial ovarian cancer: 8-year update of a randomized multicentric clinical trial. The Gruppo Oncologico Nord Ovest (GONO). Eur J Gynaecol Oncol 1992;13:36-39.
[PubMed]
3.
Arany I, Safirstein RL: Cisplatin nephrotoxicity. Semin Nephrol 2003;23:460-464.
[PubMed]
4.
Mohan IK, Khan M, Shobha JC, Naidu MU, Prayag A, Kuppusamy P, Kutala VK: Protection against cisplatin-induced nephrotoxicity by spirulina in rats. Cancer Chemother Pharmacol 2006;58:802-808.
[PubMed]
5.
Omodei D, Fontana L: Calorie restriction and prevention of age-associated chronic disease. FEBS Lett 2011;585:1537-1542.
[PubMed]
6.
Longo VD, Fontana L: Calorie restriction and cancer prevention: metabolic and molecular mechanisms. Trends Pharmacol Sci 2010;31:89-98.
[PubMed]
7.
Weindruch R, Sohal RS: Seminars in medicine of the Beth Israel Deaconess Medical Center. Caloric intake and aging. N Engl J Med 1997;337:986-994.
[PubMed]
8.
Masoro EJ: Caloric restriction and aging: an update. Exp Gerontol 2000;35:299-305.
[PubMed]
9.
Peng W, Robertson L, Gallinetti J, Mejia P, Vose S, Charlip A, Chu T, Mitchell JR: Surgical stress resistance induced by single amino acid deprivation requires Gcn2 in mice. Sci Transl Med 2012;4:118ra111.
10.
Kaushal GP, Kaushal V, Herzog C, Yang C: Autophagy delays apoptosis in renal tubular epithelial cells in cisplatin cytotoxicity. Autophagy 2008;4:710-712.
[PubMed]
11.
Do Amaral CL, Francescato HD, Coimbra TM, Costa RS, Darin JD, Antunes LM, Bianchi Mde L: Resveratrol attenuates cisplatin-induced nephrotoxicity in rats. Arch Toxicol 2008;82:363-370.
[PubMed]
12.
Maines MD, Raju VS, Panahian N: Spin trap (N-t-butyl-alpha-phenylnitrone)-mediated suprainduction of heme oxygenase-1 in kidney ischemia/reperfusion model: role of the oxygenase in protection against oxidative injury. J Pharmacol Exp Ther 1999;291:911-919.
[PubMed]
13.
Jung YJ, Lee JE, Lee AS, Kang KP, Lee S, Park SK, Lee SY, Han MK, Kim DH, Kim W: Sirt1 overexpression decreases cisplatin-induced acetylation of NF-kappaB p65 subunit and cytotoxicity in renal proximal tubule cells. Biochem Biophys Res Commun 2012;419:206-210.
[PubMed]
14.
Kim DH, Jung YJ, Lee JE, Lee AS, Kang KP, Lee S, Park SK, Han MK, Lee SY, Ramkumar KM, Sung MJ, Kim W: Sirt1 activation by resveratrol ameliorates cisplatin-induced renal injury through deacetylation of p53. Am J Physiol Renal Physiol 2011;301:F427-F435.
[PubMed]
15.
Tauchi H, Tsuboi K, Okutomi J: Age changes in the human kidney of the different races. Gerontologia 1971;17:87-97.
[PubMed]
16.
Long DA, Mu W, Price KL, Johnson RJ: Blood vessels and the aging kidney. Nephron Exp Nephrol 2005;101:e95-e99.
[PubMed]
17.
Qiao X, Chen XM, Wu D, Ding R, Wang J, Hong Q, Shi S, Li J, Xie Y, Lu Y, Wang Z: Mitochondrial pathway is responsible for aging-related increase of tubular cell apoptosis in renal ischemia/reperfusion injury. J Gerontol A Biol Sci Med Sci 2005;60:830-839.
[PubMed]
18.
Cui J, Bai XY, Shi S, Cui S, Hong Q, Cai G, Chen X: Age-related changes in the function of autophagy in rat kidneys. Age (Dordr) 2012;34:329-339.
[PubMed]
19.
Brandhorst S, et al: Short-term calorie and protein restriction provide partial protection from chemotoxicity but do not delay glioma progression. Exp Gerontol 2013;48:1120-1128.
[PubMed]
20.
Lee C, Safdie FM, Raffaghello L, Wei M, Madia F, Parrella E, Hwang D, Cohen P, Bianchi G, Longo VD: Reduced levels of IGF-I mediate differential protection of normal and cancer cells in response to fasting and improve chemotherapeutic index. Cancer Res 2010;70:1564-1572.
[PubMed]
21.
Raffaghello L, Lee C, Safdie FM, Wei M, Madia F, Bianchi G, Longo VD: Starvation-dependent differential stress resistance protects normal but not cancer cells against high-dose chemotherapy. Proc Natl Acad Sci USA 2008;105:8215-8220.
[PubMed]
22.
Santos NA, Catao CS, Martins NM, Curti C, Bianchi ML, Santos AC: Cisplatin-induced nephrotoxicity is associated with oxidative stress, redox state unbalance, impairment of energetic metabolism and apoptosis in rat kidney mitochondria. Arch Toxicol 2007;81:495-504.
[PubMed]
23.
Zhou Y, Vaidya VS, Brown RP, Zhang J, Rosenzweig BA, Thompson KL, Miller TJ, Bonventre JV, Goering PL: Comparison of kidney injury molecule-1 and other nephrotoxicity biomarkers in urine and kidney following acute exposure to gentamicin, mercury, and chromium. Toxicol Sci 2008;101:159-170.
[PubMed]
24.
Espandiari P, Zhang J, Rosenzweig BA, Vaidya VS, Sun J, Schnackenberg L, Herman EH, Knapton A, Bonventre JV, Beger RD, Thompson KL, Hanig J: The utility of a rodent model in detecting pediatric drug-induced nephrotoxicity. Toxicol Sci 2007;99:637-648.
[PubMed]
25.
Beytur A, Kose E, Sarihan ME, Sapmaz HI, Dogan Z, Cetin A, Vardi N, Turkoz Y, Ekinci N: Beneficial effects of montelukast against cisplatin-induced acute renal damage in rats. Ren Fail 2012;34:343-349.
[PubMed]
26.
Beytur A, Ciftci O, Oguz F, Oguzturk H, Yilmaz F: Montelukast attenuates side effects of cisplatin including testicular, spermatological, and hormonal damage in male rats. Cancer Chemother Pharmacol 2012;69:207-213.
[PubMed]
27.
Sawhney P, Giammona CJ, Meistrich ML, Richburg JH: Cisplatin-induced long-term failure of spermatogenesis in adult C57/Bl/6J mice. J Androl 2005;26:136-145.
[PubMed]
28.
Atessahin A, Sahna E, Turk G, Ceribasi AO, Yilmaz S, Yuce A, Bulmus O: Chemoprotective effect of melatonin against cisplatin-induced testicular toxicity in rats. J Pineal Res 2006;41:21-27.
[PubMed]
29.
Ma H, Jones KR, Guo R, Xu P, Shen Y, Ren J: Cisplatin compromises myocardial contractile function and mitochondrial ultrastructure: role of endoplasmic reticulum stress. Clin Exp Pharmacol Physiol 2010;37:460-465.
[PubMed]
30.
Kaushal GP, Kaushal V, Hong X, Shah SV: Role and regulation of activation of caspases in cisplatin-induced injury to renal tubular epithelial cells. Kidney Int 2001;60:1726-1736.
[PubMed]
31.
Nowak G: Protein kinase C-alpha and ERK1/2 mediate mitochondrial dysfunction, decreases in active Na+ transport, and cisplatin-induced apoptosis in renal cells. J Biol Chem 2002;277:43377-43388.
[PubMed]
32.
Martin-Montalvo A, de Cabo RD: Mitochondrial metabolic reprogramming induced by calorie restriction. Antioxid Redox Signal 2013;19:310-320.
[PubMed]
33.
Harhaji-Trajkovic L, Arsikin K, Kravic-Stevovic T, Petricevic S, Tovilovic G, Pantovic A, Zogovic N, Ristic B, Janjetovic K, Bumbasirevic V, Trajkovic V: Chloroquine-mediated lysosomal dysfunction enhances the anticancer effect of nutrient deprivation. Pharm Res 2012;29:2249-2263.
[PubMed]
34.
Lee C, Raffaghello L, Brandhorst S, Safdie FM, Bianchi G, Martin-Montalvo A, Pistoia V, Wei M, Hwang S, Merlino A, Emionite L, de Cabo R, Longo VD: Fasting cycles retard growth of tumors and sensitize a range of cancer cell types to chemotherapy. Sci Transl Med 2012;4:124ra27.
35.
Safdie F, Brandhorst S, Wei M, Wang W, Lee C, Hwang S, Conti PS, Chen TC, Longo VD: Fasting enhances the response of glioma to chemo- and radiotherapy. PLoS One 2012;7:e44603.
[PubMed]
36.
Lopez-Dominguez JA, Khraiwesh H, Gonzalez-Reyes JA, Lopez-Lluch G, Navas P, Ramsey JJ, de Cabo R, Buron MI, Villalba JM: Dietary fat modifies mitochondrial and plasma membrane apoptotic signaling in skeletal muscle of calorie-restricted mice. Age (Dordr) 2012;35:2027-2044.
[PubMed]
37.
Sakao Y, Kato A, Tsuji T, Yasuda H, Togawa A, Fujigaki Y, Kahyo T, Setou M, Hishida A: Cisplatin induces Sirt1 in association with histone deacetylation and increased Werner syndrome protein in the kidney. Clin Exp Nephrol 2011;15:363-372.
[PubMed]
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