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Effects of pentoxifylline administration on histomorphological parameters of streptozotocin-induced diabetic rat testes

Laboratory Animal Research volume 31, pages 111–116 (2015)Cite this article

Abstract

The effect of pentoxifylline (PTX) administration on histomorphological parameters of streptozotocin (STZ)-induced type 1 diabetes mellitus (DM) in male rat testes were evaluated. We randomly divided 40 male rats into the following four groups: group 1: control or normal glycemic (NG) rats; group 2 or NG rats that received only normal saline (NS), (NG+NS); group 3 or diabetic rats which were not treated by PTX (DM+vehicle solution (NS)); and group 4 which comprised diabetic rats treated with 50 mg/kg of PTX (DM+PTX). Type 1 DM was induced by intraperitoneal injection of STZ (55 mg/kg). Rats were held for 30 days after which the experimental group received PTX twice daily (25 mg/kg) or NS. After 14 days of treatment by PTX or NS, the left testes from all rats were extracted and prpared for histological study. Apoptotic cells, blood vessel density, and spermatogenesis were evaluated. Data were analyzed by ANOVA test. PTX-treated-diabetic rats showed a significant decrease in number of apoptotic cells and decrease in blood vessel density compared to the DM+NS rats. A significant increase in spermatogenesis was observed in the PTX-treated diabetic group, compared to the DM+NS groups. It was concluded that PTX administration to STZ-induced type 1 DM rats affected apoptotic cell number positively. Moreover, blood vessel density significantly decreased and improvements were observed in spermatogenesis.

References

  1. Amaral S, Oliveira PJ, Ramalho-Santos J. Diabetes and the impairment of reproductive function: possible role of mitochondria and reactive oxygen species. Curr Diabetes Rev 2008; 4(1): 46–54.

    Article  CAS  PubMed  Google Scholar 

  2. Thomay AA, Daley JM, Sabo E, Worth PJ, Shelton LJ, Harty MW, Reichner JS, Albina JE. Disruption of interleukin-1 signaling improves the quality of wound healing. Am J Pathol 2009; 174(6): 2129–2136.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Dey L, Attele AS, and Yuan C-S, Alternative therapies for type 2 diabetes. Textbook of complementary and alternative medicine. CRC Press 2003; 267.

    Google Scholar 

  4. Kolodny RC, Kahn CB, Goldstein HH, Barnett DM. Sexual dysfunction in diabetic men. Diabetes 1974; 23(4): 306–309.

    Article  CAS  PubMed  Google Scholar 

  5. Fairburn C. The sexual problems of diabetic men. Br J Hosp Med 1981; 25(5): 484, 487, 489–491.

    CAS  PubMed  Google Scholar 

  6. Steger RW, Rabe MB. The effect of diabetes mellitus on endocrine and reproductive function. Proc Soc Exp Biol Med 1997; 214(1): 1–11.

    Article  CAS  PubMed  Google Scholar 

  7. Mosher WD. Fecundity and infertility in the United States. Am J Public Health. 1988; 78(2): 181–182.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Aviado DM, Porter JM. Pentoxifylline: a new drug for the treatment of intermittent claudication. Mechanism of action, pharmacokinetics, clinical efficacy and adverse effects. Pharmacotherapy 1984; 4(6): 297–307.

    Article  CAS  PubMed  Google Scholar 

  9. Rendell M, Bamisedun O. Skin blood flow and current perception in pentoxifylline-treated diabetic neuropathy. Angiology 1992; 43(10): 843–851.

    Article  CAS  PubMed  Google Scholar 

  10. Aparicio NJ, Schwarzstein L, de Turner EA. Pentoxifylline (BL 191) by oral administration in the treatment of asthenozoospermia. Andrologia 1980; 12(3): 228–231.

    Article  CAS  PubMed  Google Scholar 

  11. Babaei S, Bayat M, Nouruzian M, Bayat M. Pentoxifylline improves cutaneous wound healing in streptozotocin-induced diabetic rats. Eur J Pharmacol 2013; 700(1-3): 165–172.

    Article  CAS  PubMed  Google Scholar 

  12. Soleimani Mehranjani M, Taefi R. The effects of sodium arsenite on the testis structure and sex hormones in vasectomised rats. Iran J Reprod Med. 2012; 10(6): 571–580.

    PubMed  PubMed Central  Google Scholar 

  13. Savaş C, Dindar H, Aras T, Yücesan S. Pentoxifylline improves blood flow to both testes in testicular torsion. Int Urol Nephrol 2002; 33(1): 81–85.

    Article  PubMed  Google Scholar 

  14. Najar A, Piryae A, Babaei S, Bayat M. Effect of pentoxifylline on Sertoli and Leydig cells count of experimentally induced type 1 diabetes in male rats. Ann Mil Health Sci Res. 2013; 11(3): 188–195.

    Google Scholar 

  15. Queiroz GCD, Oliveir VVG, Gueiros OG, Torres SM, Maia FCL, Tenorio BM, Morais RN, Silva JVA. Effect of pentoxifylline on the regeneration of rat testicular germ cells after heat shock. Anim. Reprod 2013; 10(1): 45–54.

    Google Scholar 

  16. Zhao Y, Tan Y, Dai J, Li B, Guo L, Cui J, Wang G, Shi X, Zhang X, Mellen N, Li W, Cai L. Exacerbation of diabetes-induced testicular apoptosis by zinc deficiency is most likely associated with oxidative stress, p38 MAPK activation, and p53 activation in mice. Toxicol Lett 2011; 200(1-2): 100–106.

    Article  CAS  PubMed  Google Scholar 

  17. Johnsen SG. Testicular biopsy score count—a method for registration of spermatogenesis in human testes: normal values and results in 335 hypogonadal males. Hormones 1970; 1(1): 2–25.

    CAS  PubMed  Google Scholar 

  18. Xu L, Kanasaki K, Kitada M, Koya D. Diabetic angiopathy and angiogenic defects. Fibrogenesis Tissue Repair 2012; 5(1): 13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Pfister F, Feng Y, vom Hagen F, Hoffmann S, Molema G, Hillebrands JL, Shani M, Deutsch U, Hammes HP. Pericyte migration: a novel mechanism of pericyte loss in experimental diabetic retinopathy. Diabetes 2008; 57(9): 2495–2502.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Guo M, Ricardo SD, Deane JA, Shi M, Cullen-McEwen L, Bertram JF. A stereological study of the renal glomerular vasculature in the db/db mouse model of diabetic nephropathy. J Anat 2005; 207(6): 813–821.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Nyengaard JR, Rasch R. The impact of experimental diabetes mellitus in rats on glomerular capillary number and sizes. Diabetologia 1993; 36(3): 189–194.

    Article  CAS  PubMed  Google Scholar 

  22. Nakagawa T, Kosugi T, Haneda M, Rivard CJ, Long DA. Abnormal angiogenesis in diabetic nephropathy. Diabetes 2009; 58(7): 1471–1478.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  Google Scholar 

  24. Rasslan R, Utiyama EM, Marques GM, Ferreira TC, da Costa VA, de Victo NC, Rasslan S, Montero EF. Inflammatory activity modulation by hypertonic saline and pentoxifylline in a rat model of strangulated closed loop small bowel obstruction. Int J Surg 2014; 12(6): 594–600.

    Article  PubMed  Google Scholar 

  25. Ersoy YE, Ayan F, Himmetoglu S. Trace element levels in ischemia-reperfusion injury after left colonic anastomosis in rats and effects of papaverine and pentoxiphylline on vascular endothelial growth factor in anastomosis healing. Acta Gastroenterol Belg 2011; 74(1): 22–27.

    CAS  PubMed  Google Scholar 

  26. Tahergorabi Z, Khazaei M. Imbalance of angiogenesis in diabetic complications: the mechanisms. Int J Prev Med 2012; 3(12): 827–838.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Cai L, Chen S, Evans T, Deng DX, Mukherjee K, Chakrabarti S. Apoptotic germ-cell death and testicular damage in experimental diabetes: prevention by endothelin antagonism. Urol Res 2000; 28(5): 342–347.

    Article  CAS  PubMed  Google Scholar 

  28. Enzlin P, Mathieu C, Van Den Bruel A, Vanderschueren D, Demyttenaere K. Prevalence and predictors of sexual dysfunction in patients with type 1 diabetes. Diabetes Care 2003; 26(2): 409–414.

    Article  PubMed  Google Scholar 

  29. Oksanen A. Testicular lesions of streptozotocin diabetic rats. Horm Res 1975; 6(3): 138–144.

    Article  CAS  PubMed  Google Scholar 

  30. Ballester J, Muñoz MC, Domínguez J, Rigau T, Guinovart JJ, Rodríguez-Gil JE. Insulin-dependent diabetes affects testicular function by FSH- and LH-linked mechanisms. J Androl 2004; 25(5): 706–719.

    Article  CAS  PubMed  Google Scholar 

  31. Ricci G, Catizone A, Esposito R, Pisanti FA, Vietri MT, Galdieri M. Diabetic rat testes: morphological and functional alterations. Andrologia 2009; 41(6): 361–368.

    Article  CAS  PubMed  Google Scholar 

  32. Bal R, Türk G, Tuzcu M, Yilmaz O, Ozercan I, Kuloglu T, Gür S, Nedzvetsky VS, Tykhomyrov AA, Andrievsky GV, Baydas G, Naziroglu M. Protective effects of nanostructures of hydrated C(60) fullerene on reproductive function in streptozotocindiabetic male rats. Toxicology 2011; 282(3): 69–81.

    Article  CAS  PubMed  Google Scholar 

  33. McKinney KA, Lewis SE, Thompson W. Persistent effects of pentoxifylline on human sperm motility, after drug removal, in normozoospermic and asthenozoospermic individuals. Andrologia 1994; 26(4): 235–240.

    Article  CAS  PubMed  Google Scholar 

  34. Terriou P, Hans E, Giorgetti C, Spach JL, Salzmann J, Urrutia V, Roulier R. Pentoxifylline initiates motility in spontaneously immotile epididymal and testicular spermatozoa and allows normal fertilization, pregnancy, and birth after intracytoplasmic sperm injection. J Assist Reprod Genet 2000; 17(4): 194–199.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

We express our appreciation to the Vice Chancellor of Research at Shahid Behesti University of Medical Sciences for financial support (grant no. 90-1-153-8183).

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Authors and Affiliations

  1. Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Abbas Piryaei & Azam Najar

  2. Cellular and Molecular Biology Research Centre, Shahid Beheshti University of Medical Sciences, Tehran, 1985717443, Iran

    Mohammad Bayat

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  1. Abbas Piryaei
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  2. Azam Najar
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Correspondence to Mohammad Bayat.

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Piryaei, A., Najar, A. & Bayat, M. Effects of pentoxifylline administration on histomorphological parameters of streptozotocin-induced diabetic rat testes. Lab Anim Res 31, 111–116 (2015). https://doi.org/10.5625/lar.2015.31.3.111

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  • DOI: https://doi.org/10.5625/lar.2015.31.3.111

Keywords

  • Diabetes mellitus
  • pentoxifylline
  • histopathology
  • testes
  • rat

Laboratory Animal Research

ISSN: 2233-7660