Effect of pentoxifylline on kidney damage induced by nitrosamine in male rats

Cyrus Jalili , Delnia Moradi, Mohammad Reza Salahshoor


Nitrosamines are well-known carcinogenic agents. Humans are exposed to nitrosamines in various ways, the most important of which is the diet. Pentoxifylline is a xanthine derivative, which is used as a drug that inhibits inflammatory factors, reduces blood viscosity, improves peripheral blood flow, and increases oxygenation of tissue. This study was designed to evaluate the effects of pentoxifylline against damage induced by nitrosamine to the kidneys of rats. In this study, 48 male rats were randomly assigned to 8 groups: control normal group and nitrosamine control treated group (40 mg/kg); pentoxifylline groups (25, 50, 100 mg/kg) and nitrosamine + pentoxifylline treated groups (25, 50, 100 mg/kg). Treatments were administered either intraperitoneally (nitrosamine) or orally (pentoxifylline) on a daily basis for 28 days. The normalized kidney weight, glomeruli characteristics, thiobarbituric acid reactive species, antioxidant capacity, kidney function indicators, and serum nitrite oxide levels were investigated. Nitrosamine administration increased kidney malondialdehyde (MDA) level, kidney weight, blood urea nitrogen (BUN), creatinine, and nitrite oxide levels and decreased significantly glomeruli number and tissue ferric reducing/antioxidant power (FRAP) level compared to the control normal group (P < 0.05). The pentoxifylline and pentoxifylline + nitrosamine treatments reduced BUN, kidney MDA level, creatinine, glomerular diameter, and nitrite oxide levels significantly at all doses and increased the glomeruli number, kidney weight, and tissue FRAP level compared to the nitrosamine control group (P < 0.05). It seems that pentoxifylline administration improved kidney injury induced by nitrosamine in rats.


Kidney; Nitrosamine; Pentoxifylline.

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Piazzoli A, Breider F, Aquillon CG, Antonelli M, von Gunten U. Specific and total N-nitrosamines formation potentials of nitrogenous micropollutants during chloramination. Water Res. 2018; 135:311-321.

Santarelli RL, Pierre F, Corpet DE. Processed meat and colorectal cancer: a review of epidemiologic and experimental evidence. Nutr Cancer. 2008;60(2):131-144.

Herrmann SS, Granby K, Duedahl-Olesen L. Formation and mitigation of N-nitrosamines in nitrite preserved cooked sausages. Food Chem. 2015;174:516-526.

Ndwberne PM, Shank RC. Induction of liver and lung tumours in rats by the simultaneous administration of sodium nitrite and morpholine. ‎Food Cosmet Toxicol. 1973; 11(5):819-825.

Moreira AJ, Ordoñez R, Cerski CT, Picada JN, García-Palomo A, Marroni NP, et al. Melatonin activates endoplasmic reticulum stress and apoptosis in rats with diethylnitrosamine-induced hepatocarcinogenesis. PLoS One. 2015;10(12):e0144517.

Rodrigo R, Rivera G. Renal damage mediated by oxidative stress: a hypothesis of protective effects of red wine. Free Radic Biol Med. 2002; 33(3):409-422.

el-Mofty M, el-Darouti M, Rasheed H, Bassiouny DA, Abdel-Halim M, Zaki NS, et al. Sulfasalazine and pentoxifylline in psoriasis: a possible safe alternative. J Dermatolog Treat. 2011; 22(1):31-37.

Navarro-González JF, Sánchez-Niño MD, Donate-Correa J, Martín-Núñez E, Ferri C, Pérez-Delgado N, et al. Effects of pentoxifylline on soluble klotho concentrations and renal tubular cell expression in diabetic kidney disease. Diabetes Care. 2018;41(8):1817-1820.

Hammerman C, Goldschmidt D, Caplan MS, Kaplan M, Schimmel MS, Eidelman AI, et al. Amelioration of ischemia-reperfusion injury in rat intestine by pentoxifylline-mediated inhibition of xanthine oxidase. J Pediatr Gastroenterol Nutr. 1999;29(1):69-74.

Jalili C, Kamani M, Roshankhah S, Sadeghi H, Salahshoor MR. Effect of Falcaria vulgaris extracts on sperm parameters in diabetic rats. Andrologia. 2018; 50(10):e13130.

Salahshoor MR, Roshankhah Sh, Hosseni P, Jalili C. Genistein improves liver damage in male mice exposed to morphine genistein improves liver damage in male mice exposed to morphine. Chin Med J (Engl). 2018;131(13):1598-604.

Roshankhah Sh, Salahshoor MR, Jalili F, Karimi F, Sohrabi M, Jalili C. Crocin effects on the nicotine-induce ovary injuries in female rat. Int J Life Sci Pharma Res. 2017;7(4):1-8.

Khorami S, Farrokhi F, Tukmechi A, Nowrozi R. Effect of pentoxifylline and vitamin E on ovarian follicles in Rats. J Shahrekord Univ Med Sci. 2013;15(3):64-73.

Oliveira TR, Oliveira GF, Simões RS, Tikazawa EH, Monteiro HP, Fagundes DJ, et al. The role of ischemic preconditioning and pentoxifylline in intestinal ischemia/reperfusion injury of rats. Acta Bras Cir. 2017;32(7):559-567.

Prasad K, Lee P. Suppression of hypercholesterolemic atherosclerosis by pentoxifylline and its mechanism. Atherosclerosis. 2007;192(2):313-322.

Jalili C, Salahshoor MR, Hoseini M, Roshankhah Sh, M Sohrabi, A Shabanizadeh. Protective effect of thymoquinone against morphine injuries to kidneys of mice. Iran J Kidney Dis. 2017;11:142-150.

Saricicek E, Celik A, Uremis N, Kilinc M. Protective effects of simvastatin, Nigella sativa oil and thmoquinone against dimethylnitrosamine-induced oxidative stress in rat kidney. Biomed Res. 2016;27(3):854-859.

Albersen M, Fandel TM, Zhang H, Banie L, Lin G, De Ridder D, et al. Pentoxifylline promotes recovery of erectile function in a rat model of postprostatectomy erectile dysfunction. Eur Urol. 2011;59(2):286-296.

Najafi H, Changizi Ashtiyani S, Madani SH, Fakhri S, Mohamadi Yarijani Z, Hazem M. Therapeutic effects of curcumin on renal tissue damages induced by ischemia/reperfusion in rats. Koomesh. 2015;16(2):273-281.

Jalili C, Makalani F, Roshankhah Sh, Sohrabi Kh, Salahshoor MR. Protective effect of resveratrol against morphine damage to kidneys of mice. Int J Morphol. 2017;35(4):1409-1415.

Verhaegen A, Van Gaal L. Do E‐cigarettes induce weight changes and increase cardiometabolic risk? A signal for the future. Obes Rev. 2017;18(10):1136-1146.

Davila-Esqueda ME, Martinez-Morales F. Pentoxifylline diminishes the oxidative damage to renal tissue induced by streptozotocin in the rat. Exp Diabesity Res. 2004;5(4):245-251.

Verma A, Ahmed B, Anwar F, Rahman M, Patel DK, Kaithwas G, et al. Novel glycoside from Wedelia calendulacea inhibits diethyl nitrosamine-induced renal cancer via downregulating the COX-2 and PEG 2 through nuclear factor-κB pathway. Inflammopharmacology. 2017;25(1):159-175.

Ozer MK, Asci H, Oncu M, Yesilot S, Savran M, Bayram D, et al. Effects of pentoxifylline on amikacin-induced nephrotoxicity in rats. Ren Fail. 2009;31(2):134-139.

Khan N, Sharma S, Alam A, Saleem M, Sultana S. Tephrosia pursuer ameliorates N-diethyl nitrosamine and potassium bromated-mediated renal oxidative stress and toxicity in Wistar rats. Pharmacol Toxicol. 2001;88(6):294-299.

Chen YM, Lin SL, Chiang WC, Wu KD, Tsai TJ. Pentoxifylline ameliorates proteinuria through suppression of renal monocyte chemoattractant protein-1 in patients with proteinuric primary glomerular diseases. Kidney Int 2006; 69(8):1410-1415.

Hebels DG, Briedé JJ, Khampang R, Kleinjans JC, de Kok TM. Radical mechanisms in nitrosamine-and nitrosamide-induced whole-genome gene expression modulations in Caco-2 cells. Toxicol Sci. 2010;116(1):194-205.

Garcia FA, Rebouças JF, Balbino TQ, da Silva TG, de Carvalho-Júnior CH, Cerqueira GS, et al. Pentoxifylline reduces the inflammatory process in diabetic rats: relationship with decreases of pro-inflammatory cytokines and inducible nitric oxide synthase. Int J Inflam (Lond). 2015;12:33-42.


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