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Reza Salahshoor, M., Faramarzi, A., Roshankhah, S., & Jalili, C. (2019). The protective effect of Pentoxifylline on testopathy in male rats following Dimethyl Nitrosamine administration: An experimental study. International Journal of Reproductive BioMedicine (IJRM), 17(10). https://doi.org/10.18502/ijrm.v17i10.5292
https://doi.org/10.18502/ijrm.v17i10.5292
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authors
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Mohammad Reza Salahshoor
Mohammad Reza Salahshoor
Department of Anatomical Sciences, Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran
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Azita Faramarzi
Azita Faramarzi
Department of Anatomical Sciences, Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran; Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
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Shiva Roshankhah
Shiva Roshankhah
Department of Anatomical Sciences, Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran
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Cyrus Jalili
Cyrus Jalili
Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
Published Date
- Oct 1, 2019
The protective effect of Pentoxifylline on testopathy in male rats following Dimethyl Nitrosamine administration: An experimental study
Abstract
This article has been retracted.
Background: Nitrosamines as a carcinogenic agent has unfavorable effects on some of the male reproductive parameters. Pentoxifylline (PX) is a xanthine derivative used as a drug inhibiting the inflammatory factors, reducing blood viscosity, improving peripheral blood flow, and so on.
Objective: The aim of the present study is to evaluate the effects of PX against Dimethyl nitrosamine (DMN)-inducing the damage to the reproductive parameter of male rats.
Materials and Methods: In this experimental study, 48 male Wistar rats (8 wk, 220- 250 gr) were randomly assigned to eight groups (n = 6/each): normal control and DMN control groups (40 mg/kg); PX groups (25, 50, 100 mg/kg), and DMN + PX groups (25, 50, 100 mg/kg). Treatments were administered intraperitoneally and the gavage applied daily for 28 days. The sperm parameters, spermatogenesis index, total antioxidant capacity, testosterone level, and seminiferous tube diameter were assessed.
Results: The values of all parameters reduced significantly in the DMN control group compared to the normal control group (p < 0.001). The PX and PX + DMN treatments at all entirely doses improved all parameters significantly compared to the DMN control group (p < 0.001).
Conclusion: DMN caused detrimental effects on reproductive parameters. Also, no significant modifications were observed in PX treatments at all doses compared to the normal control group. PX compensated the toxic effect of DMN on reproductive parameters.
Key words: Dimethyl nitrosamine, Reproductive, Pentoxifylline, Rat.
References
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[12] Moein MR, Khalili MA, Davoudi A. The effect of oral administration of Pentoxifylline on sperm motility of asthenozoospermic ejaculates from men with or without testicular varicoceles. Iran J Reprod Med 2005; 3: 25–29.
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[14] Johnsen SG. Testicular biopsy score count–a method for registration of spermatogenesis in human testes: normal values and results in 335 hypogonadal males. Hormone Research in Paediatrics 1970; 1: 2–25.
[15] Aitken RJ, Roman SD. Antioxidant systems and oxidative stress in the testes. Oxid Med Cell Longev 2008; 1: 15–24.
[16] Sadik NAH, EL-Maraghy SA, Ismail MF. Diethylnitrosamineinduced hepatocarcinogenesis in rats: possible chemoprevention by blueberries. Afr J Biochem Res 2008; 2: 081–087.
[17] Barroso G, Morshedi M, Oehninger S. Analysis of DNA fragmentation, plasma membrane translocation of phosphatidylserine and oxidative stress in human spermatozoa. Hum Reprod 2000; 15: 1338–1344.
[18] Houston BJ, Nixon B, Martin JH, De Iuliis GN, Trigg NA, Bromfield EG, et al. Heat exposure induces oxidative stress and DNA damage in the male germ line. Biol Reprod 2018; 98: 593–606.
[19] Leisegang K, Henkel R, Agarwal A. Redox regulation of fertility in aging male and the role of antioxidants: a savior or stressor. Curr Pharm Des 2017; 23: 4438–4450.
[20] Khan S, Telang AG, Malik JK. Arsenic-induced oxidative stress, apoptosis and alterations in testicular steroidogenesis and spermatogenesis in Wistar rats: ameliorative effect of curcumin. Wudpecker J Pham Phamacol 2013; 2: 33–48.
[21] Jalili C, Kamani M, Roshankhah S, Sadeghi H, Salahshoor MR. Effect of falcaria vulgaris extracts on sperm parameters in diabetic rats. Andrologia 2018; 50: e13130.
[22] Armstrong JS, Rajasekaran M, Chamulitrat W, Gatti P, Hellstrom WJ, Sikka SC. Characterization of reactive oxygen species induced effects on human spermatozoa movement and energy metabolism. Free Radic Biol Med 1999; 26: 869–880.
[23] Gomez E, Irvine DS, Aitken RJ. Evaluation of a spectrophotometric assay for the measurement of malondialdehyde and 4-hydroxyalkenals in human spermatozoa: relationships with semen quality and sperm function. Int J Androl 1998; 21: 81–94.
[24] Bansal AK, Bilaspuri GS. Impacts of oxidative stress and antioxidants on semen functions. Vet Med Int 2010; 2010: 1–7.
[25] Adeleke GE, Adaramoye OA. Betulinic acid protects against N-nitrosodimethylamine-induced redox imbalance in testes of rats. Redox Rep 2017; 22: 556–562.
[26] Hassanpour H, Mirshokraei P, Tajik P, Haghparast A. In vitro effects of pentoxifylline on kinematic parameters, capacitation, and acrosome reaction of ram epididymal sperm. Comparative Clinical Pathology 2010; 19: 377–381.
[27] Marques GM, Rasslan R, Belon AR, Carvalho JG, Felice Neto R, Rasslan S, et al. Pentoxifylline associated to hypertonic saline solution attenuates inflammatory process and apoptosis after intestinal ischemia/reperfusion in rats. Acta Cir Bras 2014; 29: 735–741.
[28] Griveau JF, Lobel B, Laurent MC, Michardière L, Le Lannou D. Interest of pentoxifylline in ICSI with frozen–thawed testicular spermatozoa from patients with non-obstructive azoospermia. Reprod Biomed Online 2006; 12: 14–18.
[29] Nabi A, Khalili MA, Talebi AR, Mangoli E, Yari N, Nottola SA, et al. In-vitro application of pentoxifylline preserved ultrastructure of spermatozoa after vitrification in asthenozoospermic patients. Urol J 2017; 14: 4038–4043.
[30] Yadav AS, Bhatnagar D. Chemo-preventive effect of Star anise in N-nitrosodiethylamine initiated and phenobarbital promoted hepato-carcinogenesis. Chem Biol Interact 2007; 169: 207–214.
[31] Salahshoor MR, Khazaei M, Jalili C, Keivan M. Crocin improves damage induced by nicotine on a number of reproductive parameters in male mice. Int J Fertil Steril 2016; 10: 71–78.
[32] Huang F, Ning H, Xin QQ, Huang Y, Wang H, Zhang ZH, et al. Melatonin pretreatment attenuates 2-bromopropane induced testicular toxicity in rats. Toxicology 2009; 256: 75–82.
[33] Aziz N, Saleh RA, Sharma RK, Lewis-Jones I, Esfandiari N, Thomas Jr AJ, et al. Novel association between sperm reactive oxygen species production, sperm morphological defects, and the sperm deformity index. Fertil Steril 2004; 81: 349–354.
[34] Dutra TCE, da Silva DS, Lazzari VM, Stein A, da Cunha Filho JS. Activation of the mobility of human spermatozoa with the use of pentoxifylline: effects on spermal DNA. Hum Reprod Arch 2017; 32: 1–7.
[35] Lin HY, Yeh CT. Controlled release of pentoxifylline from porous chitosan-pectin scaffolds. Drug Deliv 2010; 17: 313– 321.
[2] Tremellen K. Oxidative stress and male infertility-a clinical perspective. Hum Reprod Update 2008; 14: 243–258.
[3] Agarwal A, Roychoudhury S, Sharma R, Gupta S, Majzoub A, Sabanegh E. Diagnostic application of oxidation-reduction potential assay for measurement of oxidative stress: clinical utility in male factor infertility. Reprod Biomed Online 2017; 34: 48–57.
[4] Yu K, Rajan VP, Dai N. Kinetics and pathways for nitrosamine formation in amino acid-based carbon dioxide capture systems. Int J Greenh Gas Con 2018; 75: 52–62.
[5] Gushgari AJ, Halden RU. Critical review of major sources of human exposure to N-nitrosamines. Chemosphere 2018; 210: 1124–1136.
[6] Ezhuthupurakkal PB, Ariraman S, Arumugam S, Subramaniyan N, Muthuvel SK, Kumpati P, et al. Anticancer potential of ZnO nanoparticle-ferulic acid conjugate on Huh-7 and HepG2 cells and diethyl nitrosamine induced hepatocellular cancer on Wistar albino rat. Nanomedicine 2018; 14: 415–428.
[7] Yang CS, Yoo JS, Ishizaki H, Hong JY. Cytochrome P450IIE1: roles in nitrosamine metabolism and mechanisms of regulation. Drug Metab Rev 1990; 22: 147–159.
[8] Jayakumar S, Madankumar A, Asokkumar S, Raghunandhakumar S, Gokula dhas K, Kamaraj S, et al. Potential preventive effect of carvacrol against diethylnitrosamine induced hepatocellular carcinoma in rats. Mol Cell Biochem 2012; 360: 51–60.
[9] Jalili C, Khani F, Salahshoor MR, Roshankhah S. Protective effect of curcumin against nicotine-induced damage on reproductive parameters in male mice. Int J Morphol 2014; 32: 844–849.
[10] Van Wagner LB, Koppe SW, Brunt EM, Gottstein J, Gardikiotes K, Green RM, et al. Pentoxifylline for the treatment of non-alcoholic steatohepatitis: a randomized controlled trial. Ann Hepatol 2011; 10: 277–286.
[11] Prasad K, Lee P. Suppression of hypercholesterolemic atherosclerosis by pentoxifylline and its mechanism. Atherosclerosis 2007; 192: 313–322.
[12] Moein MR, Khalili MA, Davoudi A. The effect of oral administration of Pentoxifylline on sperm motility of asthenozoospermic ejaculates from men with or without testicular varicoceles. Iran J Reprod Med 2005; 3: 25–29.
[13] Organization WH. WHO laboratory manual for the examination and processing of human semen. 5th Ed. German: World Health Organization; 2010.
[14] Johnsen SG. Testicular biopsy score count–a method for registration of spermatogenesis in human testes: normal values and results in 335 hypogonadal males. Hormone Research in Paediatrics 1970; 1: 2–25.
[15] Aitken RJ, Roman SD. Antioxidant systems and oxidative stress in the testes. Oxid Med Cell Longev 2008; 1: 15–24.
[16] Sadik NAH, EL-Maraghy SA, Ismail MF. Diethylnitrosamineinduced hepatocarcinogenesis in rats: possible chemoprevention by blueberries. Afr J Biochem Res 2008; 2: 081–087.
[17] Barroso G, Morshedi M, Oehninger S. Analysis of DNA fragmentation, plasma membrane translocation of phosphatidylserine and oxidative stress in human spermatozoa. Hum Reprod 2000; 15: 1338–1344.
[18] Houston BJ, Nixon B, Martin JH, De Iuliis GN, Trigg NA, Bromfield EG, et al. Heat exposure induces oxidative stress and DNA damage in the male germ line. Biol Reprod 2018; 98: 593–606.
[19] Leisegang K, Henkel R, Agarwal A. Redox regulation of fertility in aging male and the role of antioxidants: a savior or stressor. Curr Pharm Des 2017; 23: 4438–4450.
[20] Khan S, Telang AG, Malik JK. Arsenic-induced oxidative stress, apoptosis and alterations in testicular steroidogenesis and spermatogenesis in Wistar rats: ameliorative effect of curcumin. Wudpecker J Pham Phamacol 2013; 2: 33–48.
[21] Jalili C, Kamani M, Roshankhah S, Sadeghi H, Salahshoor MR. Effect of falcaria vulgaris extracts on sperm parameters in diabetic rats. Andrologia 2018; 50: e13130.
[22] Armstrong JS, Rajasekaran M, Chamulitrat W, Gatti P, Hellstrom WJ, Sikka SC. Characterization of reactive oxygen species induced effects on human spermatozoa movement and energy metabolism. Free Radic Biol Med 1999; 26: 869–880.
[23] Gomez E, Irvine DS, Aitken RJ. Evaluation of a spectrophotometric assay for the measurement of malondialdehyde and 4-hydroxyalkenals in human spermatozoa: relationships with semen quality and sperm function. Int J Androl 1998; 21: 81–94.
[24] Bansal AK, Bilaspuri GS. Impacts of oxidative stress and antioxidants on semen functions. Vet Med Int 2010; 2010: 1–7.
[25] Adeleke GE, Adaramoye OA. Betulinic acid protects against N-nitrosodimethylamine-induced redox imbalance in testes of rats. Redox Rep 2017; 22: 556–562.
[26] Hassanpour H, Mirshokraei P, Tajik P, Haghparast A. In vitro effects of pentoxifylline on kinematic parameters, capacitation, and acrosome reaction of ram epididymal sperm. Comparative Clinical Pathology 2010; 19: 377–381.
[27] Marques GM, Rasslan R, Belon AR, Carvalho JG, Felice Neto R, Rasslan S, et al. Pentoxifylline associated to hypertonic saline solution attenuates inflammatory process and apoptosis after intestinal ischemia/reperfusion in rats. Acta Cir Bras 2014; 29: 735–741.
[28] Griveau JF, Lobel B, Laurent MC, Michardière L, Le Lannou D. Interest of pentoxifylline in ICSI with frozen–thawed testicular spermatozoa from patients with non-obstructive azoospermia. Reprod Biomed Online 2006; 12: 14–18.
[29] Nabi A, Khalili MA, Talebi AR, Mangoli E, Yari N, Nottola SA, et al. In-vitro application of pentoxifylline preserved ultrastructure of spermatozoa after vitrification in asthenozoospermic patients. Urol J 2017; 14: 4038–4043.
[30] Yadav AS, Bhatnagar D. Chemo-preventive effect of Star anise in N-nitrosodiethylamine initiated and phenobarbital promoted hepato-carcinogenesis. Chem Biol Interact 2007; 169: 207–214.
[31] Salahshoor MR, Khazaei M, Jalili C, Keivan M. Crocin improves damage induced by nicotine on a number of reproductive parameters in male mice. Int J Fertil Steril 2016; 10: 71–78.
[32] Huang F, Ning H, Xin QQ, Huang Y, Wang H, Zhang ZH, et al. Melatonin pretreatment attenuates 2-bromopropane induced testicular toxicity in rats. Toxicology 2009; 256: 75–82.
[33] Aziz N, Saleh RA, Sharma RK, Lewis-Jones I, Esfandiari N, Thomas Jr AJ, et al. Novel association between sperm reactive oxygen species production, sperm morphological defects, and the sperm deformity index. Fertil Steril 2004; 81: 349–354.
[34] Dutra TCE, da Silva DS, Lazzari VM, Stein A, da Cunha Filho JS. Activation of the mobility of human spermatozoa with the use of pentoxifylline: effects on spermal DNA. Hum Reprod Arch 2017; 32: 1–7.
[35] Lin HY, Yeh CT. Controlled release of pentoxifylline from porous chitosan-pectin scaffolds. Drug Deliv 2010; 17: 313– 321.