Evaluation of the Effect of Pentoxifylline on Cisplatin-Induced Testicular Toxicity in Rats

Abstract

Chemotherapy is associated with male infertility. Cisplatin (cis-diamminedichloro-platinum (II) (CDDP) as a chemotherapy medication used to treat a number of cancers has been reported to most likely induce testicular toxicity. Administration of antioxidants, such as pentoxifylline (PTX) may reduce some Adverse Drug Reactions (ADRs) of CDDP. Therefore, this study investigated the potentially protective effects of PTX on CDDP-induced testicular toxicity in adult male rats. For this purpose, 42 male rats were randomly divided into 7 groups. The rats were orally pretreated with PTX at the 3 doses of 75, 150, and 300 mg/kg once a day for 14 successive days. On the 14^th day of the study, they were intraperitoneally (IP) administered with a single dose of CDDP (7 mg/kg). Finally, the sperm/testis parameters, serum levels of reproductive hormones, including testosterone, Luteinizing Hormone (LH), and Follicle Stimulating Hormone (FSH) as the pivotal endocrine factors controlling testicular functions, and histopathological changes of testis tissue were examined. Pretreatment with the two doses of 75 and 150 mg/kg PTX indicated significant increases in the sperm count and motility induced by CDDP administration. The right and significantly left testis weights were decreased following the treatment with 300 mg/kg of PTX plus CDDP. However, 75 mg/kg of PTX plus CDDP showed the best near-to-normal histopathological features. The results demonstrated that PTX alone enhanced some parameters, such as the sperm count, while reducing other parameters, including sperm fast motility and germ layer thickness. Furthermore, despite testosterone or LH levels, the mean serum FSH level was significantly augmented by the doses of 75 and 150 mg/kg. It was concluded that PTX administration cannot reduce CDDP-induced testicular toxicity even at high doses (e.g., 300 mg/kg), while it seemed to partially intensify CDDP toxicity effects at a dose of 75 mg/kg. Thus, further research is required in this regard.

Keywords: Antioxidant; Chemotherapy; Histopathological feature; Sperm motility; Testicular toxicity.

Fig. 1

The mean weight of the animals at the beginning and end of the * indicated significant (p<0.05) difference compared with control.

Fig. 2

Serum testosterone levels in study groups. * Indicated significant (p<0.05) difference compared with control.

Fig. 3

The mean luteinizing hormone (LH) in blood. * Indicated significant (p<0.05) difference compared with control.

Fig. 4

The mean follicle stimulating hormone (FSH) in blood. * Indicated significant (p<0.05) difference compared with control; and ^# indicated significant (p<0.05) differences compared with CDDP group.

Fig. 5

Microscopic views of hematoxylin and eosin (H & E) - stained rat testes with ×40 magnification. (A) Control group. (B) Rats treated with cisplatin (CDDP). (C) Rats treated by CDDP and PTX (75mg/kg). (D) Rats treated by CDDP and PTX (150 mg/kg). (E) Rats treated by CDDP and PTX (300 mg/kg). (F) Rats treated with PTX (300 mg/kg).