Research Article
Bir Kemoterapotik Ajan Olan Bleomisine Maruz Kalan Ratlarda Adenozinin Kompetetif Antagonisti Olan Teofilinin Uygulanması Sonrasında Sperm Parametrelerindeki Değişimler
Abstract
Bu çalışmanın yapılmasındaki amaç, bir kemoterapotik ajan olan bleomisine (BLM) maruz bırakılan ratlarda metilksantin türevi olan teofilinin (THP) sperm parametreleri üzerinde ne gibi etkiler göstereceğini belirlemektir. Çalışma 32 adet erkek rat üzerinde yapıldı. Grup 1’deki ratlara sadece steril serum fizyolojik intratrakeal yoldan uygulandı. Grup 2’deki ratlara, 7.5 mg/kg BLM intratrakeal olarak tek doz uygulandı. Grup 3’deki ratlara, 7.5 mg/kg BLM intratrakeal olarak tek doz uygulandı. İlave olarak 14 gün boyunca 75 mg/kg/gün dozunda THP intraperitoneal yoldan uygulandı. Grup 4’deki ratlara, 14 gün boyunca 75 mg/kg/gün dozunda THP intraperitoneal yoldan uygulandı. Motilite, sperm yoğunluğu, anormal sperm ve ölü sperm oranlarına bakıldı. BLM uygulanan ratların sperm parametrelerinde ciddi bozulmalar tespit edildi. THP uygulanan ratların sperm parametrelerinde sadece motilitede anlamlı artışlar oluşturduğu, ancak sperm yoğunluğu, anormal sperm ve ölü sperm sayısı üzerinde anlamlı olarak değişiklikler yapmadığı tespit edildi. Bu çalışmada THP sadece motiliteyi arttırmıştır. Motilite dışında sperm parametreleri üzerinde olumlu bir etkisi yoktu.
Keywords
References
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Razavi S., Khadivi F., Hashemi F., Bakhtiari A., 2019. Effect of zinc on spermatogenesis and sperm chromatin condensation in bleomycin, etoposide, cisplatin treated rats. Cell J, 20, 521-526. 7. Schilsky RL., Lewis BJ., Sherins RJ., Young RC., 1980. Gonadal dysfunction in patients receiving chemotherapy for cancer. Ann Intern Med, 93, 109-114. 8. Madabhavi I., Modi G., Patel A., Anand A., Panchal H., Parikh S., 2017. Pulmonary toxicity following bleomycin use: A single-center experience. J Cancer Res Ther, 3, 466-470. 9. Bokuchava MA., Skobeleva NI., 1980. The biochemistry and technology of tea manufacture. Crit Rev Food Sci Nutr, 12, 303-370. 10. Heidemann HT., Müller S., Mertins L., Stepan G., Hoffmann K., Ohnhaus EE., 1989. Effect of aminophylline on cisplatin nephrotoxicity in the rat. Br J Pharmacol, 97, 313-318. 11. Modlinger PS., Welch WJ., 2003. Adenosine A1 receptor antagonists and the kidney. Curr Opin Nephrol Hypertens, 12, 497-502. 12. Osswald H., 1975. Renal effects of adenosine and their inhibition by theophyline in dogs. Naunyn Schmiedebergs Arch Pharmacol, 288, 79-86. 13. Osswald H., 1983. Adenosine and renal function. Regulatory Function of Adenosine. Springer US, 399-415. 14. Tengowski MW., Feng D., Sutovsky M., Sutovsky P., 2007. Differential expression of genes encoding constitutive and inducible 20S proteasomal core subunits in the testis and epididymis of theophylline- or 1,3-dinitrobenzene-exposed rats. Biol Reprod, 76, 149-163. 15. Weinberger MA., Friedman L., Farber TM., Moreland FM., Peters EL., Gilmore CE., Khan MA., 1978. Testicular atrophy and impaired spermatogenesis in rats fed high levels of the methylxanthines caffeine, theobromine, or theophylline. J Environ Pathol Toxicol, 1, 669-688. 16. Nantel F., Monaco L., Foulkes NS., Masquilier D., LeMeur M., Henriksen K., Dierich A., Parvinen M., Sassone-Corsi P., 1996. Spermiogenesis deficiency and germ-cell apoptosis in CREM-mutant mice. Nature, 380, 159-162. 17. Morrissey RE., Collins JJ., Lamb JC., Manus AG., Gulati DK., 1988. Reproductive effects of theophylline in mice and rats. Fundam Appl Toxicol, 10, 525-36. 18. Aksu EH., Akman O., Özkaraca M., Ömür AD., Uçar Ö., 2015. Effect of Maclura pomifera extract against cisplatin‐induced damage in reproductive system of male rats. Kafkas Univ Vet Fak Derg, 21, 397-403. 19. Belhan S., Özkaraca M., Kandemir FM., Gülyüz F., Yıldırım S., Ömür AD., Yener Z. 2017. Effectiveness of hesperidin on methotrexate induced testicular toxicity in rats. Kafkas Univ Vet Fak Derg, 23, 779-786. 20. Turk G., Atessahin A., Sonmez M., Ceribasi AO., Yuce A., 2008. Improvement of cisplatin‐induced injuries to sperm quality, the oxidant–antioxidant system, and the histologic structure of the rat testis by ellagic acid. Fertil Steril, 89, 1474-1481. 21. Garbers DL., 1971. Effects of phosphodiesterase inhibitors and cyclic nucleotides on sperm respiration and motility. Biochem, 10, 1825-1831. 22. Hoskins DD., Hall ML., Munsterman D., 1975. Induction of motility of immature bovine spermatozoa by cyclic AMP phosphodiesterase inhibitors and seminal plasma. Biol Reprod, 13, 168-176. 23. Fraser LR., Monks NJ., 1990. Cyclic nucleotides and mammalian sperm capacitation. J Reprod Fertil Suppl, 42, 9-21. 24. Monks NJ., Fraser LR., 1987. Phosphodiesterase activity of mouse sperm incubated under conditions that modulate fertilizing potential in vitro. Gamete Res, 18, 85-97. 25. Fraser LR., 1979. Accelerated mouse sperm penetration in vitro in the presence of caffeine. J Reprod Fertil, 57, 377-384. 26. Loughlin KR., Agarwal A., 1992. The use of theophylline to enhance sperm function. Ach Androl, 28, 99-103. 27. Negri P., Grechi E., Tomasi A., Fabbri E., Capuzzo A., 1996. Effectiveness of pentoxifylline in semen preparation for intrauterine insemination. Hum Reprod, 11, 1236-1239. 28. Kızılay F., Altay B., 2018. Effect of phosphodiesterase Type-5 inhibitors on semen parameters. Androl Bul, 20, 54-60. 29. Drobnis EZ., Nangia AK., 2017. Male Reproductive Functions Disrupted by Pharmacological Agents. Adv Exp Med Biol, 1034, 13-24.
Changes in Sperm Parameters Following Administration of Theophylline, a Competitive Antagonist of Adenosine in Rats Exposed to Bleomycin, a Chemotherapeutic Agent
Abstract
The aim of the present study is to determine the effects of theophylline (THP), a methylxanthine derivative, on the sperm parameters of rats exposed to bleomycin (BLM) as a chemotherapeutic agent. The study was performed on 32 male rats. The rats in Group 1 were treated only with sterile saline intratracheally. The rats in Group 2 were administered a single dose of 7.5 mg/kg of BLM intratracheally. The rats in Group 3 received a single dose of 7.5 mg/kg of BLM intratracheally. In addition, THP was administered to rats in Group 3 intraperitoneally at a dose of 75 mg/kg/ day for 14 days. The rats in group 4 were administered an intraperitoneal injection of THP at a dose of 75 mg/kg/day for 14 days. Motility, sperm density, abnormal sperm and dead sperm rates were examined. Significant deteriorations were observed in sperm parameters of rats that were administered BLM. In the sperm parameters of THP treated rats, it was determined that it only increased motility, but did not significantly change sperm density, abnormal sperm and dead sperm count. In this study, THP only increased motility. There was no positive effect on sperm parameters except motility.
Keywords
References
- 1. Du L., Sanchez C., Chen M., Edwards DJ., Shen B., 2000. The biosynthetic gene cluster for the antitumor drug bleomycin from Streptomyces verticillus ATCC15003 supporting functional interactions between nonribosomal peptide synthetases and a polyketide synthase. Chem Biol, 7, 623-642. 2. Jules-Elysee K., White DA., 1990. Bleomycin induced pulmonary toxicity. Clin Chest Med, 11, 1-20. 3. Mano MS., Guimaraes JL., Sutmöller SF., Reiriz AB., Sutmöller CS., Di Leo A., 2006. Extensive deep vein thrombosis as a complication of testicular cancer treated with the BEP protocol (bleomycin, etoposide and Cisplatin): case report. Saao Paulo Med J, 124, 343-345. 4. Amirshahi T., Najafi G., Nejati V., 2014. Protective effect of royal jelly on fertility and biochemical parameters in bleomycin- induced male rats. Iran J Reprod Med, 12, 209-216. 5. Ojo OO., 2017. Induction of Apoptosis by Bleomycin Compound in testis of Swiss albino mice. AIJRFANS, 19, 21-27. 6. Razavi S., Khadivi F., Hashemi F., Bakhtiari A., 2019. Effect of zinc on spermatogenesis and sperm chromatin condensation in bleomycin, etoposide, cisplatin treated rats. Cell J, 20, 521-526. 7. Schilsky RL., Lewis BJ., Sherins RJ., Young RC., 1980. Gonadal dysfunction in patients receiving chemotherapy for cancer. Ann Intern Med, 93, 109-114. 8. Madabhavi I., Modi G., Patel A., Anand A., Panchal H., Parikh S., 2017. Pulmonary toxicity following bleomycin use: A single-center experience. J Cancer Res Ther, 3, 466-470. 9. Bokuchava MA., Skobeleva NI., 1980. The biochemistry and technology of tea manufacture. Crit Rev Food Sci Nutr, 12, 303-370. 10. Heidemann HT., Müller S., Mertins L., Stepan G., Hoffmann K., Ohnhaus EE., 1989. Effect of aminophylline on cisplatin nephrotoxicity in the rat. Br J Pharmacol, 97, 313-318. 11. Modlinger PS., Welch WJ., 2003. Adenosine A1 receptor antagonists and the kidney. Curr Opin Nephrol Hypertens, 12, 497-502. 12. Osswald H., 1975. Renal effects of adenosine and their inhibition by theophyline in dogs. Naunyn Schmiedebergs Arch Pharmacol, 288, 79-86. 13. Osswald H., 1983. Adenosine and renal function. Regulatory Function of Adenosine. Springer US, 399-415. 14. Tengowski MW., Feng D., Sutovsky M., Sutovsky P., 2007. Differential expression of genes encoding constitutive and inducible 20S proteasomal core subunits in the testis and epididymis of theophylline- or 1,3-dinitrobenzene-exposed rats. Biol Reprod, 76, 149-163. 15. Weinberger MA., Friedman L., Farber TM., Moreland FM., Peters EL., Gilmore CE., Khan MA., 1978. Testicular atrophy and impaired spermatogenesis in rats fed high levels of the methylxanthines caffeine, theobromine, or theophylline. J Environ Pathol Toxicol, 1, 669-688. 16. Nantel F., Monaco L., Foulkes NS., Masquilier D., LeMeur M., Henriksen K., Dierich A., Parvinen M., Sassone-Corsi P., 1996. Spermiogenesis deficiency and germ-cell apoptosis in CREM-mutant mice. Nature, 380, 159-162. 17. Morrissey RE., Collins JJ., Lamb JC., Manus AG., Gulati DK., 1988. Reproductive effects of theophylline in mice and rats. Fundam Appl Toxicol, 10, 525-36. 18. Aksu EH., Akman O., Özkaraca M., Ömür AD., Uçar Ö., 2015. Effect of Maclura pomifera extract against cisplatin‐induced damage in reproductive system of male rats. Kafkas Univ Vet Fak Derg, 21, 397-403. 19. Belhan S., Özkaraca M., Kandemir FM., Gülyüz F., Yıldırım S., Ömür AD., Yener Z. 2017. Effectiveness of hesperidin on methotrexate induced testicular toxicity in rats. Kafkas Univ Vet Fak Derg, 23, 779-786. 20. Turk G., Atessahin A., Sonmez M., Ceribasi AO., Yuce A., 2008. Improvement of cisplatin‐induced injuries to sperm quality, the oxidant–antioxidant system, and the histologic structure of the rat testis by ellagic acid. Fertil Steril, 89, 1474-1481. 21. Garbers DL., 1971. Effects of phosphodiesterase inhibitors and cyclic nucleotides on sperm respiration and motility. Biochem, 10, 1825-1831. 22. Hoskins DD., Hall ML., Munsterman D., 1975. Induction of motility of immature bovine spermatozoa by cyclic AMP phosphodiesterase inhibitors and seminal plasma. Biol Reprod, 13, 168-176. 23. Fraser LR., Monks NJ., 1990. Cyclic nucleotides and mammalian sperm capacitation. J Reprod Fertil Suppl, 42, 9-21. 24. Monks NJ., Fraser LR., 1987. Phosphodiesterase activity of mouse sperm incubated under conditions that modulate fertilizing potential in vitro. Gamete Res, 18, 85-97. 25. Fraser LR., 1979. Accelerated mouse sperm penetration in vitro in the presence of caffeine. J Reprod Fertil, 57, 377-384. 26. Loughlin KR., Agarwal A., 1992. The use of theophylline to enhance sperm function. Ach Androl, 28, 99-103. 27. Negri P., Grechi E., Tomasi A., Fabbri E., Capuzzo A., 1996. Effectiveness of pentoxifylline in semen preparation for intrauterine insemination. Hum Reprod, 11, 1236-1239. 28. Kızılay F., Altay B., 2018. Effect of phosphodiesterase Type-5 inhibitors on semen parameters. Androl Bul, 20, 54-60. 29. Drobnis EZ., Nangia AK., 2017. Male Reproductive Functions Disrupted by Pharmacological Agents. Adv Exp Med Biol, 1034, 13-24.
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Details
| Primary Language | English |
|---|---|
| Subjects | Health Care Administration |
| Journal Section | Araştırma Makaleleri |
| Authors | |
| Publication Date | December 25, 2019 |
| Published in Issue | Year 2019 Volume: 14 Issue: 3 |