Preventive effect of pentoxifylline on contrast‑induced acute kidney injury in hypercholesterolemic rats

Yang,Shi‑Kun; Duan,Shao‑Bin; Pan,Peng; Xu,Xiang‑Qing; Liu,Na; Xu,Jun

doi:10.3892/etm.2014.2132

Preventive effect of pentoxifylline on contrast‑induced acute kidney injury in hypercholesterolemic rats

Authors:
- Shi‑Kun Yang
- Shao‑Bin Duan
- Peng Pan
- Xiang‑Qing Xu
- Na Liu
- Jun Xu
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Affiliations: Department of Nephrology, Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China
Published online on: December 15, 2014 https://doi.org/10.3892/etm.2014.2132
Pages: 384-388

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Abstract

Oxidative stress is an important mechanism of contrast‑induced acute kidney injury (CIAKI). The optimal strategy to prevent CIAKI remains unclear. The aim of the present study was to assess the effect of pentoxifylline, a nonspecific phosphodiesterase inhibitor, on the prevention of CIAKI. A total of 32 healthy male Sprague‑Dawley rats were randomly divided into normal dietary group (NN; n=8) and a high cholesterol‑supplemented dietary group (HN; 4% cholesterol and 1% cholic acid; n=24). At the end of eight weeks, the rats in the high cholesterol diet group were randomly divided into three subgroups (n=8 in each group). CIAKI was induced in two of the subgroups via intravenous injection of the radiocontrast media iohexol (10 ml/kg). Pentoxifylline (50 mg/kg) was administered to one of the iohexol‑treated groups via intraperitoneal injection 12 h prior to and following contrast media (CM) injection. Kidney function parameters and oxidative stress markers were then measured. The renal pathological changes were evaluated using hematoxylin and eosin staining and scored semi‑quantitatively. In iohexol‑injected rats, serum creatinine (Scr), renal pathological scores, renal malondialdehyde (MDA) content, renal NADPH oxidase activity, fractional excretion of sodium (FENa%) and fractional excretion of potassium (FEK%) were significantly increased (P<0.01). The Scr, histologic scores, renal MDA content, NADPH oxidase activity, FENa% and FEK% in the rats treated with pentoxifylline prior to iohexol were observed to be reduced compared with those in rats treated with iohexol alone (P<0.01). This suggests that pentoxifylline significantly attenuates renal injuries, including tubular necrosis and proteinaceous casts induced by CM. It may be concluded that pentoxifylline protected the renal tissue from the nephrotoxicity induced by low‑osmolar CM via an antioxidant effect.

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1	Itoh Y, Yano T, Sendo T and Oishi R: Clinical and experimental evidence for prevention of acute renal failure induced by radiographic contrast media. J Pharmacol Sci. 97:473–488. 2005. View Article : Google Scholar : PubMed/NCBI
2	Aspelin P, Aubry P, Fransson SG, Strasser R, Willenbrock R and Berg KJ: NEPHRIC Study Investigators: Nephrotoxic effects in high-risk patients undergoing angiography. N Engl J Med. 348:491–499. 2003. View Article : Google Scholar : PubMed/NCBI
3	Seeliger E, Sendeski M, Rihal CS and Persson PB: Contrast-induced kidney injury: mechanisms, risk factors, and prevention. Eur Heart J. 33:2007–2015. 2012. View Article : Google Scholar : PubMed/NCBI
4	Russo D, Minutolo R, Cianciaruso B, Memoli B, Conte G and De Nicola L: Early effects of contrast media on renal hemodynamics and tubular function in chronic renal failure. J Am Soc Nephrol. 6:1451–1458. 1995.PubMed/NCBI
5	Perianayagam MC, Liangos O, Kolyada AY, et al: NADPH oxidase p22phox and catalase gene variants are associated with biomarkers of oxidative stress and adverse outcomes in acute renal failure. J Am Soc Nephrol. 18:255–263. 2007. View Article : Google Scholar
6	Duan SB, Liu GL, Chen GC, Wang P, Pan P and Xu XQ: Aged rats are susceptible to nephrotoxicity induced by iodinated contrast media. Ren Fail. 35:150–154. 2013. View Article : Google Scholar
7	Duan SB, Yang SK, Zhou QY, et al: Mitochondria-targeted peptides prevent on contrast-induced acute kidney injury in the rats with hypercholesterolemia. Ren Fail. 35:1124–1129. 2013. View Article : Google Scholar : PubMed/NCBI
8	Roozbeh J, Hamidian Jahromi A, Sharifian M, Pakfetrat M and Afshariani R: Protective effect of pentoxifylline on contrast induced nephropathy. Saudi J Kidney Dis Transpl. 19:985–986. 2008.PubMed/NCBI
9	Nasiri-Toosi Z, Dashti-Khavidaki S, Khalili H and Lessan-Pezeshki M: A review of the potential protective effects of pentoxifylline against drug-induced nephrotoxicity. Eur J Clin Pharmacol. 69:1057–1073. 2013. View Article : Google Scholar
10	Firouzi A, Eshraghi A, Shakerian F, et al: Efficacy of pentoxifylline in prevention of contrast-induced nephropathy in angioplasty patients. Int Urol Nephrol. 44:1145–1149. 2012. View Article : Google Scholar
11	Yang D, Lin S, Yang D, Wei L and Shang W: Effects of short- and long-term hypercholesterolemia on contrast-induced acute kidney injury. Am J Nephrol. 35:80–89. 2012. View Article : Google Scholar
12	Yang DW, Jia RH, Yang DP, Ding GH and Huang CX: Dietary hypercholesterolemia aggravates contrast media-induced nephropathy. Chin Med J (Engl). 117:542–546. 2004.
13	Lin SL, Chiang WC, Chen YM, Lai CF, Tsai TJ and Hsieh BS: The renoprotective potential of pentoxifylline in chronic kidney disease. J Chin Med Assoc. 68:99–105. 2005. View Article : Google Scholar : PubMed/NCBI
14	Duan S, Zhou X, Liu F, et al: Comparative cytotoxicity of high-osmolar and low-osmolar contrast media on HKCs in vitro. J Nephrol. 19:717–724. 2006.PubMed/NCBI
15	Rudnick MR and Goldfarb S: Pathogenesis of contrast-induced nephropathy: experimental and clinical observations with an emphasis on the role of osmolality. Rev Cardiovasc Med. 4(Suppl 5): S28–S33. 2003.PubMed/NCBI
16	Ahmad A, Mondello S, Di Paola R, et al: Protective effect of apocynin, a NADPH-oxidase inhibitor, against contrast-induced nephropathy in the diabetic rats: a comparison with N-acetylcysteine. Eur J Pharmacol. 674:397–406. 2012. View Article : Google Scholar
17	Benko A, Fraser-Hill M, Magner P, et al: Canadian Association of Radiologists: consensus guidelines for the prevention of contrast-induced nephropathy. Can Assoc Radiol J. 58:79–87. 2007.PubMed/NCBI
18	Quintavalle C, Brenca M, De Micco F, et al: In vivo and in vitro assessment of pathways involved in contrast media-induced renal cells apoptosis. Cell Death Dis. 2:e1552011. View Article : Google Scholar : PubMed/NCBI
19	Samlaska CP and Winfield EA: Pentoxifylline. J Am Acad Dermatol. 30:603–621. 1994. View Article : Google Scholar : PubMed/NCBI
20	Dávila-Esqueda ME and Martínez-Morales F: Pentoxifylline diminishes the oxidative damage to renal tissue induced by streptozotocin in the rat. Exp Diabesity Res. 5:245–251. 2004. View Article : Google Scholar
21	Costantini TW, Deree J, Peterson CY, et al: Pentoxifylline modulates p47phox activation and downregulates neutrophil oxidative burst through PKA-dependent and -independent mechanisms. Immunopharmacol Immunotoxicol. 32:82–91. 2010. View Article : Google Scholar
22	Savic V, Vlahovic P, Djordjevic V, Mitic-Zlatkovic M, Avramovic V and Stefanovic V: Nephroprotective effects of pentoxifylline in experimental myoglobinuric acute renal failure. Pathol Biol (Paris). 50:599–607. 2002. View Article : Google Scholar
23	Tyagi P, Sharma P, Sharma BC, Puri AS, Kumar A and Sarin SK: Prevention of hepatorenal syndrome in patients with cirrhosis and ascites: a pilot randomized control trial between pentoxifylline and placebo. Eur J Gastroenterol Hepatol. 23:210–217. 2011. View Article : Google Scholar : PubMed/NCBI
24	de Moura FJ, Leal PP, de Souza Furtado R, Muniz-Junqueira MI and Veiga JP: Pentoxifylline prevents the meglumine antimonate-induced renal toxicity in rats, but not that induced by the inorganic antimony pentachloride. Toxicology. 243:66–74. 2008. View Article : Google Scholar