Journal of Mazandaran University of Medical Sciences (May 2024)
Influence of Pentoxifylline on the Damage of Sperm Parameters Induced by Etoposide in Mice
Abstract
Background and purpose: Although recent advances in cancer treatment have increased patient survival and improved quality of life, exposure to chemotherapy drugs leads to significant fertility problems in children with cancer. Etoposide is a chemotherapy drug that is widely used in the treatment of various types of cancer; However, it destroys healthy cells, especially male germ cells that are multiplying rapidly and continuously, and leads to infertility. In the present study, the antioxidant effect of pentoxifylline on the disorder caused by etoposide on the sperm parameters of adult male NMRI mice was investigated. Materials and methods: 24 adult male NMRI mice with an average weight of 35±2gr (n=6) were randomly allocated to the following groups (n=6): control, etoposide (1mg/kg), pentoxifylline (100mg/kg) and etoposide + pentoxifylline and treated with daily intraperitoneal injection for 35 days. At the end of the treatment period, mice were anesthetized with ketamine-xylazine solution, and the left caudal region of epididymis was transferred to a 3cm plate containing culture medium (HamsF10) in a 37°C incubator to examine sperm parameters including the number, motility, morphology, viability and tail length of the sperm. The denaturation of sperm DNA using acridine orange staining and the maturation rate of sperm nucleus using aniline blue staining method was measured. The left testicle was removed and used to calculate daily sperm production. After taking blood from the heart and preparing serum, total antioxidant capacity, and malondialdehyde level were also measured. The data were statistically analyzed with SPSS software, one-way ANOVA, and Tukey's test, and the difference in means was considered significant at the P<0.05 level. Results: A significant decrease in the mean percentage of progressive sperms and a significant increase in the mean percentage of in situ and immotile sperms were observed in the etoposide group compared to the control group (P<0.001). Also, a significant decrease in the mean count, viability, daily sperm production, tail length, and normal morphology of sperm was observed in the etoposide group compared to the control group (P<0.001). The total antioxidant capacity also decreased significantly in the etoposide group compared to the control group (P<0.001). The level of serum malondialdehyde showed a significant increase in the etoposide group compared to the control group (P<0.001). There was no significant difference in the mean percentage of sperm DNA damage and sperm nucleus maturation in the etoposide group compared to the control group (P<0.05). Simultaneous treatment of pentoxifylline with etoposide significantly improved the aforementioned parameters compared to the etoposide group. Conclusion: The results in the etoposide treatment group showed a significant decrease in sperm parameters and total antioxidant capacity, as well as a significant increase in malondialdehyde levels. The toxicity induced by etoposide through the induction of apoptosis, oxidative stress, and lipid peroxidation is considered the primary cause of the resulting damage, as evidenced by the study results. Pentoxifylline is believed to have mitigated the harmful effects of etoposide on sperm parameters and oxidative stress by leveraging its antioxidant properties to reduce oxidative stress.
