- Open Access
Effects of pentoxifylline administration on histomorphological parameters of streptozotocin-induced diabetic rat testes
Laboratory Animal Research volume 31, pages111–116(2015)
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.
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.
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.
Dey L, Attele AS, and Yuan C-S, Alternative therapies for type 2 diabetes. Textbook of complementary and alternative medicine. CRC Press 2003; 267.
Kolodny RC, Kahn CB, Goldstein HH, Barnett DM. Sexual dysfunction in diabetic men. Diabetes 1974; 23(4): 306–309.
Fairburn C. The sexual problems of diabetic men. Br J Hosp Med 1981; 25(5): 484, 487, 489–491.
Steger RW, Rabe MB. The effect of diabetes mellitus on endocrine and reproductive function. Proc Soc Exp Biol Med 1997; 214(1): 1–11.
Mosher WD. Fecundity and infertility in the United States. Am J Public Health. 1988; 78(2): 181–182.
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.
Rendell M, Bamisedun O. Skin blood flow and current perception in pentoxifylline-treated diabetic neuropathy. Angiology 1992; 43(10): 843–851.
Aparicio NJ, Schwarzstein L, de Turner EA. Pentoxifylline (BL 191) by oral administration in the treatment of asthenozoospermia. Andrologia 1980; 12(3): 228–231.
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.
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.
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.
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.
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.
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.
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.
Xu L, Kanasaki K, Kitada M, Koya D. Diabetic angiopathy and angiogenic defects. Fibrogenesis Tissue Repair 2012; 5(1): 13.
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.
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.
Nyengaard JR, Rasch R. The impact of experimental diabetes mellitus in rats on glomerular capillary number and sizes. Diabetologia 1993; 36(3): 189–194.
Nakagawa T, Kosugi T, Haneda M, Rivard CJ, Long DA. Abnormal angiogenesis in diabetic nephropathy. Diabetes 2009; 58(7): 1471–1478.
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.
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.
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.
Tahergorabi Z, Khazaei M. Imbalance of angiogenesis in diabetic complications: the mechanisms. Int J Prev Med 2012; 3(12): 827–838.
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.
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.
Oksanen A. Testicular lesions of streptozotocin diabetic rats. Horm Res 1975; 6(3): 138–144.
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.
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.
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.
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.
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.
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).
About this article
Cite this article
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) doi:10.5625/lar.2015.31.3.111
- Diabetes mellitus