ORIGINAL ARTICLE Therapeutic effect of pentoxifylline on reproductive parameters in diabetic male mice S. A. Feyli 1 , A. Ghanbari 1 & Z. Keshtmand 2 1 Fertility and Infertility Research Center, Kermanshah University of Medical Sciences, Tehran, Iran; 2 Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran Keywords Apoptosis—diabetes—mice—pentoxifylline— sperm parameters Correspondence Ali Ghanbari, Fertility and Infertility Research Center, Kermanshah University of Medical Sciences, PO Box 1568, Kermanshah, Iran. Tel-Fax: +98 831 4281563; E-mail: aghanbari@kums.ac.ir and Zahra Keshtmand, Department of Biology, Science and Research Branch, Islamic Azad University, PO Box 6771844681, Tehran, Iran. Tel-Fax: +98 9187340515; E-mail: zkeshtmand2001@yahoo.com Accepted: March 7, 2016 doi: 10.1111/and.12604 Summary In this study, we aimed to investigate the effects of pentoxifylline (PTX) on male reproductive parameters in diabetic mice. Male adult mice (n = 24) were divided into control and three experimental groups (n = 6) including Diabetic, Diabetic + PTX and PTX groups. Diabetes was induced by single injection of streptozotocin (60 mg kg À1 ). PTX was administered intraperitoneally at the dose of 12 mg kg À1 for 14 days 1 week after diabetes induction. Serum levels of testosterone and blood glucose were determined and collected spermatozoa from cauda epididymidis analysed. Based on histological slides prepared from testis, the diameter of seminiferous tubules was determined using Motic camera and software and also apoptosis using TUNEL assay. Data were analysed using one-way ANOVA method, and P < 0.05 was considered statistically significant. The mean of seminiferous tubules diameter, final body weight, testis weight, sperm parameters and testosterone hormone level in PTX-treated diabetic group indicated a significant increase compared to diabetic one, whereas apop- tosis index and blood glucose were decreased in this comparison (P < 0.05). These results suggest that intraperitoneal administration of PTX is a potentially beneficial agent to reduce testicular damage and improves sperm parameters in diabetic mice by decreasing the ratio of apoptosis. Introduction Diabetes mellitus is a serious metabolic disorder that is characterised by increasing amount of blood sugar and also exerts many functional and structural complications on male reproductive system addressing in both clinical and experimental studies (Meyer et al., 2000; Baccetti et al., 2002; Soudamani et al., 2005; Delfino et al., 2007). Although vast number of drug therapy-based researches have been performed to treat the disease and to save its drastic side effects, respectively, these two medical goals remain as public health challenges leading researchers to find more powerful drugs in this respect. Pentoxifylline (PTX) drug has been developed since 1972 for the treatment of vascular diseases by improving arterial outflow. PTX as a methylxanthine derivate inhi- bits breakdown of cyclic Adenosine Monophosphate (AMP) and subsequently provokes both cellular glycoly- sis generation and endogenous adenosine triphosphate ATP production that lead to increased sperm movements consequently (Suji & Sivakami, 2003). Pentoxifylline also takes part in anti-inflammatory responses through inhibition of pro-inflammatory cyto- kine secretion of interleukin 1-beta, interleukin-6 and other mediators (Garcia et al., 2015). These characteristics of the drug introduce it for improving the peripheral vas- cular side effects of diabetes, management of microalbu- minuria in diabetic patients and delaying the progression of the disease (Rocha-Santos et al., 2015). According to the hazardous effects of diabetes on male reproductive system and beneficial effect of PTX either to this system or the other signs of the disease, this study was conducted to evaluate the possible effect of PTX on male reproductive system of diabetic mice. Material and methods Animals Twenty-four male 2-month-old BALB/c pubertal mice (25–32 g) were obtained from Pasteur Institute (Tehran- Iran) and kept in the temperature of 22 Æ 2 °C, under © 2016 Blackwell Verlag GmbH 1 Andrologia 2016, xx, 1–7