Doxorubicin-Induced Reproductive Dysfunction in Wistar Rats: Biochemical, Oxidative Stress, Enzymatic and Spermatological Evaluation with Hesperidin Amelioration
DOI:
https://doi.org/10.48165/ijvsbt.22.5.25Keywords:
Doxorubicin, Hesperidin, Oxidative stress, Reproductive toxicity, Serum biochemical assayAbstract
Doxorubicin (DOX) is a widely used chemotherapeutic agent whose clinical application is limited by its adverse effects on male reproductive function. The present study was undertaken to evaluate the protective effect of hesperidin against DOX-induced reproductive toxicity in 40 adult male Wistar rats. The rats were randomly allocated to five groups, each of 8 animals, comprising a control group, a DOX-treated group, a DOX plus benazepril group, and DOX plus hesperidin (100 and 200 mg/kg) groups. Treatments were administered for 28 days, after which serum biochemical parameters, testicular oxidative stress markers, lactate dehydrogenase activity and epididymal sperm characteristics were evaluated. Doxorubicin administration caused significant reproductive dysfunction, evidenced by increased serum alkaline phosphatase and testicular malondialdehyde levels, decreased testosterone, superoxide dismutase and testicular LDH activities, and marked deterioration in sperm count, motility, viability and morphology. Co-administration of hesperidin significantly ameliorated these alterations in a dose-dependent manner, with the higher dose (200 mg/kg) restoring most parameters close to normal values and exhibiting greater protective efficacy than benazepril. These findings demonstrate that hesperidin effectively attenuates doxorubicin induced reproductive toxicity through its antioxidant and gonadoprotective actions and may serve as a promising adjunctive agent for preserving male reproductive function during doxorubicin-based chemotherapy.
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Afolabi, O. K., Wusu, A. D., Ugbaja, R., & Fatoki, J. O. (2018). Aluminium phosphide-induced testicular toxicity through oxidative stress in Wistar rats: Ameliorative role of hesperidin. Toxicology Research and Application, 2, 2397847318812794.
Ahmed, Z. A., Abtar, A. N., Othman, H. H., & Aziz, T. A. (2019). Effects of quercetin, sitagliptin alone or in combination in testicular toxicity induced by doxorubicin in rats. Drug Design, Development and Therapy, 3321–3329.
Carvalho, C., Santos, R. X., Cardoso, S., Correia, S., Oliveira, P. J., Santos, M. S., & Moreira, P. I. (2009). Doxorubicin: The good, the bad and the ugly effect. Current Medicinal Chemistry, 16(25), 3267–3285.
Eid, R. A., Khalil, M. A., Soliman, M. M., & Zaki, M. S. A. (2016). Captopril protects against cisplatin-induced testicular toxicity through antioxidant and anti-inflammatory mechanisms. Andrologia, 48(6), 686–694.
El-Maddawy, Z. K., & Abd El Naby, W. S. H. (2019). Protective effects of zinc oxide nanoparticles against doxorubicin-induced testicular toxicity and DNA damage in male rats. Toxicology Research, 8(5), 654–662.
Elsaeed, E. M., Elbanhawy, R. A., Ibrahim, F. M., Abd El-Aziz, E. H., & Gadallah, A. I. (2023). Protective effects of enalapril alone and in combination with paricalcitol on diabetic testicular dysfunction in streptozotocin-induced diabetic rats. Life Sciences, 315, 121374.
Garg, A., Garg, S., Zaneveld, L. J. D., & Singla, A. (2001). Chemistry and pharmacology of the citrus bioflavonoid hesperidin. Phytotherapy Research, 15(8), 655–669.
Guleş, O., Dogan, G., Ercinc, U. H., & Eren, U. (2022). Effects of quercetin against doxorubicin-induced testicular toxicity in male rats. Biology Bulletin, 49(3), 203–213.
Hafez, E. S. E. (1970). Reproduction and breeding techniques for laboratory animals. Lea & Febiger.
Hari Priya, B., Ramya, B., Bora, S., Shivakumar, P., Rohan, A., Vagdevi, T., & Amoolya Rao, A. (2024). Mitigating cyclophosphamide-associated gonadotoxicity in male Wistar rats: Exploring the therapeutic potential of hesperidin. Frontiers in Veterinary Science, 11, 1376225.
Hozayen, W. G. (2012). Effect of hesperidin and rutin on doxorubicin-induced testicular toxicity in male rats. International Journal of Food and Nutrition Science, 1(1), 31–42.
Hozayen, W. G., Abou Seif, H. S., & Amin, S. (2014). Protective effects of rutin and/or hesperidin against doxorubicin-induced hepatotoxicity. International Journal of Clinical Nutrition, 2(1), 11–17.
Kaya, K., Ciftci, O., Cetin, A., Dogan, H., & Başak, N. (2015). Hesperidin protects testicular and spermatological damages induced by cisplatin in rats. Andrologia, 47(7), 793–800.
Khamis, T., Hegazy, A. A., El-Fatah, S. S. A., Abdelfattah, E. R., Abdelfattah, M. M. M., Fericean, L. M., & Arisha, A. H. (2023). Hesperidin mitigates cyclophosphamide-induced testicular dysfunction via altering the hypothalamic-pituitary-gonadal axis and testicular steroidogenesis, inflammation, and apoptosis in male rats. Pharmaceuticals, 16(2), 301.
Laila, I. M. I., Kassem, S. H., & Diab, M. S. E. M. (2023). Ameliorative effect of hesperidin against high-dose sildenafil-induced liver and testicular oxidative stress and altered gene expression in male rats. Laboratory Animal Research, 39(1), 22.
Licata, S., Saponiero, A., Mordente, A., & Minotti, G. (2000). Doxorubicin metabolism and toxicity in human myocardium: Role of cytoplasmic deglycosidation and carbonyl reduction. Chemical Research in Toxicology, 13(5), 414–420.
Minotti, G., Menna, P., Salvatorelli, E., Cairo, G., & Gianni, L. (2004). Anthracyclines: Molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacological Reviews, 56(2), 185–229.
Mohamed, R. H., Karam, R. A., Hagrass, H. A., Amer, M. G., & Abd El-Haleem, M. R. (2015). Anti-apoptotic effect of spermatogonial stem cells on doxorubicin-induced testicular toxicity in rats. Gene, 561(1), 107–114.
Mustafa, S., Ijaz, M. U., ul Ain, Q., Afsar, T., Almajwal, A., Shafique, H., & Razak, S. (2022). Isorhamnetin: A flavonoid, attenuated doxorubicin-induced testicular injury via regulation of steroidogenic enzymes and apoptotic signaling gene expression in male rats. Toxicology Research, 11(3), 475–485.
Olayinka, E. T., & Adewole, K. E. (2021). In vivo and in silico evaluation of the ameliorative effect of hesperidin on finasteride-induced testicular oxidative stress in Wistar rats. Toxicology Mechanisms and Methods, 31(2), 81–89.
Owumi, S. E., Ijadele, A. O., Arunsi, U. O., & Odunola, O. A. (2020). Luteolin abates reproductive toxicity mediated by the oxido-inflammatory response in doxorubicin-treated rats. Toxicology Research and Application, 4, 2397847320972040.
Patil, L., & Balaraman, R. (2009). Effect of melatonin on doxorubicin-induced testicular damage in rats. International Journal of PharmTech Research, 1(3), 879–884.
Rizk, S. M., Zaki, H. F., & Mina, M. A. (2014). Propolis attenuates doxorubicin-induced testicular toxicity in rats. Food and Chemical Toxicology, 67, 176–186.
Slott, V. L., Suarez, J. D., & Perreault, S. D. (1991). Rat sperm motility analysis: Methodologic considerations. Reproductive Toxicology, 5(6), 449–458.
Soliman, H. A., Ahmed, R. R., Gomaa, H. A., & Ali, A. T. (2014). Assessment of the chemo-preventive effects of various plant constituents against doxorubicin-induced toxicity in rats. Journal of American Science, 10(9), 153–164.
Swamy, A. V., Gulliaya, S., Thippeswamy, A., Koti, B. C., & Manjula, D. V. (2012). Cardioprotective effect of curcumin against doxorubicin-induced myocardial toxicity in albino rats. Indian Journal of Pharmacology, 44(1), 73–77.
Tekin, S., & Çelebi, F. (2022). Investigation of the effect of hesperidin on some reproductive parameters in testicular toxicity induced by bisphenol A. Andrologia, 54(10), e14562.
Trivedi, P. P., Tripathi, D. N., & Jena, G. B. (2011). Hesperetin protects testicular toxicity of doxorubicin in rat: Role of NFκB, p38 and caspase-3. Food and Chemical Toxicology, 49(4), 838–847.
Turedi, S., Yulug, E., Alver, A., Kutlu, O., & Kahraman, C. (2015). Effects of resveratrol on doxorubicin-induced testicular damage in rats. Experimental and Toxicologic Pathology, 67(3), 229–235.
Wyrobek, A. J., & Bruce, W. R. (1975). Chemical induction of sperm abnormalities in mice. Proceedings of the National Academy of Sciences, 72(11), 4425–4429.
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