Ameliorative Effects of Curcumin on Ciprofloxacin-Induced Testicular Toxicity: A Study on Reproductive Hormones, Oxidative Stress, and Histological Changes in Adult Male Mice

Abstract

Ciprofloxacin, a widely used fluoroquinolone antibiotic, has been associated with testicular toxicity, characterized by oxidative stress and hormonal imbalances that impact male reproductive health. Curcumin, a natural antioxidant and anti-inflammatory agent, has shown potential in mitigating these effects. This study aimed to evaluate the ameliorative effects of curcumin on ciprofloxacin-induced testicular toxicity in adult male mice, focusing on reproductive hormones, oxidative stress, and histological changes. Thirty mice were divided into six groups, receiving varying doses of ciprofloxacin and curcumin over 30 days. Hormonal assays for testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were performed, alongside assessments of oxidative stress markers like malondialdehyde (MDA) and histopathological analyses of testicular tissue. Results showed a significant reduction in FSH and testosterone levels in ciprofloxacin-treated mice, with curcumin ameliorating these effects in co-treatment groups. MDA levels, an indicator of oxidative stress, were elevated in ciprofloxacin-only groups but significantly reduced in curcumin-treated groups. Histological examination revealed that curcumin protected against ciprofloxacin-induced testicular damage. In conclusion, curcumin demonstrated significant protective effects against ciprofloxacin-induced testicular toxicity by normalizing reproductive hormone levels, reducing oxidative stress, and preserving testicular architecture. These findings suggest curcumin as a potential therapeutic agent for preventing fluoroquinolone-related reproductive toxicity.

References

1. Drake RL, Vogl W, Mitchell AW, Gray H. Gray’s anatomy for students. 3rd ed. Elsevier Health Sciences; 2015. Vol. 1, Issue 2, p. 948-961.
2. Kumar V, Abbas AK, Aster JC. Robbins basic pathology. 9th ed. Elsevier Saunders; 2013. Vol. 9, Issue 5, p. 578 - 592.
3. Robert F, Sargis R. The hypothalamic-pituitary-gonadal axis and male infertility. Endocrinol Metab Clin North Am. 2008;37(3):745-62.
4. Bosky A. Advances in male infertility: Current trends in diagnosis and treatment. Fertil Res Pract. 2022;8(1):35-45.
5. Guyton AC, Hall JE. Textbook of medical physiology. 12th ed. Elsevier Saunders; 2011. Vol. 12, Issue 1, p. 1095-1112.
6. He W, Zhang Z, Zhang Y, Cui Y. Risk factors for male infertility: A review. Reprod Biol Endocrinol. 2013;11(1):1-8.
7. Semet A, Paci M, Saïas-Magnan J, Metzler-Guillemain C, Boissier R, Lejeune H, et al. The impact of drugs on male fertility: A review. Andrology. 2017;5(4):640-63.
8. Abs R, Verhelst J, Maeyaert J, Van Buyten JP, Opsomer F, Adriaensen H, et al. Endocrine consequences of long-term intrathecal administration of opioids. J Clin Endocrinol Metab. 2000;85(6):2215-22.
9. Chen H, Zhao H, Liu C, Zhu W, Gong L. Drug-induced reproductive toxicity in male mice: Mechanisms and therapeutic strategies. Reprod Toxicol. 2013;40:1-10.
10. Rovira C, Rodríguez-Martínez H, Peña-Martínez E. Effects of drugs on male fertility: Mechanisms and therapeutic approaches. Int J Androl. 2012;35(4):599-610.
11. Akubue PI, Mittal GC, Aguwa CN. Preliminary pharmacological study of some Nigerian medicinal plants. J Ethnopharmacol. 1980;2(3):277-88.
12. Olorunfemi PO, Ighodaro OM, Akinloye O. Evaluation of the effect of curcumin on plasma glucose and lipid profile of streptozotocin-induced diabetic rats. Niger J Nat Prod Med. 2005;9:47-50.
13. Nwozo SO, Okameme PE, Oyinloye BE. Hypoglycemic and hepatoprotective effects of ethanolic leaf extract of Cnestis ferruginea. Afr J Biomed Res. 2004;7(1):45-50.
14. Tietz NW. Fundamentals of Clinical Chemistry. 5th ed. W.B. Saunders Company; 1995. Vol. 5, Issue 3, p. 765-781.
15. Buege JA, Aust SD. Microsomal lipid peroxidation. In: Methods in Enzymology. Vol. 52. Academic Press; 1978. p. 302-10.
16. Mohammed A, Ndukwe KC, Okeke CE. Histological techniques: Methods and uses in research. J Med Res Pract. 2014;4(2):17-25.
17. Sudhakar PV, Ravikumar R, Jayakumar T. Ciprofloxacin-induced oxidative stress and its impact on testicular functions in rats: ameliorative effect of vitamin C. Iran J Basic Med Sci. 2020;23(6):780-6.
18. Kocahan S, Doğan Z, Erman F. Curcumin protects against doxorubicin-induced testicular toxicity in rats. Andrologia. 2019;51(11)
19. Kumar M, Mandal A, Dev A. Ameliorative effects of curcumin on fluoroquinolone-induced reproductive toxicity in male rats. J Basic Clin Physiol Pharmacol. 2021;32(2):231-8.
20. Tanyildizi S, Bozkurt Y. Effects of antibiotics on spermatogenesis and histological changes in testes of rats. J Clin Exp Invest. 2020;11(2):42-7.
21. Fouad AA, Jresat I. Hepatoprotective effect of curcumin and dimethyl fumarate against ciprofloxacin-induced liver injury in rats. Hum Exp Toxicol. 2016;35(1):111-20.
22. Yadav A, Kumar V, Singh S. Curcumin attenuates oxidative stress and inflammation in cisplatin-induced testicular damage in rats. Biomed Pharmacother. 2020;129:110139.
23. Aldarmahi A. Ciprofloxacin-induced testicular toxicity: histological and immunohistochemical study. J Microsc Ultrastruct. 2018;6(3):150-6.