Protective effect of baicalin on cyclophosphamide-induced oxidative stress and morphologic damage in testis tissue

Gülseren Altay Aznavur; Doç.dr. Şehkar Oktay; Esin Ak

Protective effect of baicalin on cyclophosphamide-induced oxidative stress and morphologic damage in testis tissue

Abstract

The purpose of this study is to examine the effect of baicalin on cyclophosphamide (CP)-induced testicular damage in rats. Twenty-eight Wistar albino rats were assigned to the control, baicalin, CP, and CP+Baicalin groups. A single dose of CP (200 mg/kg) was induced intraperitoneally (i.p.) in the CP and CP+Baicalin groups. Baicalin (100 mg/kg/day, i.p.) was administered in the baicalin and CP+ Baicalin groups for 6 days. After sacrification, the testes, epididymis and blood samples were taken. Testis tissues were investigated for general morphology, proliferating, and apoptotic cells. Oxidative stress parameters in testis tissue and hormone levels in serum were examined by biochemical analysis. Sperm analysis was performed on smear samples obtained from the epididymis. In CP + Baicalin group, decreases in both the number of abnormal spermatozoa and degeneration of seminiferous tubules were observed compared to the CP group. Also, decreased apoptotic cells and increased proliferative cells were detected in these seminiferous tubules. Furthermore, the treatment with Baicalin reversed the changes observed in the markers of oxidative damage including malondialdehyde, total oxidant status, and oxidative stress index, and markers of the antioxidant defense system including glutathione, total antioxidant capacity, superoxide dismutase, and catalase except for glutathione s-transferase (GST) in testicular tissue. Decreased serum levels of follicle-stimulating hormone, luteinizing hormone, and testosterone related to CP significantly improved in CP + Baicalin group. Conclusion: Baicalin attenuates CP-induced testicular damage by inhibiting oxidative stress possibly due to its antioxidant properties. Considering on the proposed beneficial effects of Baicalin against testicular damage induced by CP, it might have the potential to be a promising agent for male infertility related to chemotherapy.

Keywords

References

[1] Ghobadi E, Moloudizargari M, Asghari MH, Abdollahi M. The mechanisms of cyclophosphamide-induced testicular toxicity and the protective agents. Expert Opin Drug Metab Toxicol. 2017; 13(5): 525-536. https://doi.org/10.1080/17425255.2017.1277205
[2] Zhao Q, Chen XY, Martin C. Scutellaria baicalensis, the golden herb from the garden of Chinese medicinal plants. Sci Bull (Beijing). 2016; 61(18): 1391-1398. https://doi.org/10.1007/s11434-016-1136-5
[3] Tan N, Sun CX, Zhu HJ, Li DY, Huang SG, He SD. Baicalin attenuates adriamycin-induced nephrotic syndrome by regulating fibrosis procession and inflammatory reaction. Genes Genomics. 2021; 43(9): 1011-1021. https://doi.org/10.1007/s13258-021-01107-x
[4] Sawicka E, Długosz A, Rembacz KP, Guzik A. The effects of coenzyme Q10 and baicalin in cisplatin-induced lipid peroxidation and nitrosative stress. Acta Pol Pharm. 2013; 70(6): 977-985.
[5] El-Ela SRA,Zaghloul RA, Eissa LA.Promising cardioprotective effect of baicalin in doxorubicin-induced cardiotoxicity through targeting toll-like receptor 4/nuclear factor-KB and Wnt/β-catenin pathways.Nutrition.2022; 102: 111732. http://doi.org/10.1016/j.nut.2022.111732.
[6] Liu Y, Hong Z, Chen P, Wang J, Zhou Y, Huang J. Baicalin inhibits growth and induces apoptosis of human osteosarcoma cells by suppressing the AKT pathway. Oncol Lett. 2019; 18(3): 3188-3194. http://doi.org/10.3892/ol.2019.10617
[7] Fouad AA, Qutub HO, Jresat I. Dose-dependent protective effect of baicalin against testicular torsion-detorsion in rats. Andrologia. 2017; 49(1). https://doi.org/10.1111/and.12580
[8] Akilah A, Balaha M, Rahman MA, Hedya S. Apigenin and baicalin, each alone or in low-dose combination, attenuated chloroquine induced male infertility in adult rats. Thai J Pharm Sci. 2018; 42: 118-128.

[9] Guo X, Chi S, Cong X, Li H, Jiang Z, Cao R, Tian W. Baicalin protects sertoli cells from heat stress-induced apoptosis via activation of the Fas/FasL pathway and Hsp72 expression. Reprod Toxicol. 2015; 57: 196-203. https://doi.org/10.1016/j.reprotox.2015.06.049
[10] Sui J, Feng Y, Li H, Cao R, Tian W, Jiang Z. Baicalin protects mouse testis from injury induced by heat stress. J Therm Biol. 2019; 82: 63-69. https://doi.org/10.1016/j.jtherbio.2019.03.009
[11] Tekeli MY, Eraslan G, Bayram LÇ, Aslan C, Çalımlı S. The protective effects of baicalin and chrysin against emamectin benzoate-induced toxicity in Wistar albino rats. Environ Sci Pollut Res Int. 2023; 30(18): 53997-54021. https://doi.org/10.1007/s11356-023-26110-5
[12] Fan R, Dai F, Zhang C, Zhou L, Qiu X, Li Y. Baicalin attenuates continuous activation of β-catenin induced by lipopolysaccharide (LPS) and depression complicated by infertility in male rats. Evid Based Complement Alternat Med. 2022; 2022: 2112359. http://doi.org/10.1155/2022/2112359
[13] Kaypaklı O, Gür M, Harbalıoğlu H, Şeker T, Selek Ş. High morning blood pressure surge is associated with oxidative stress and paraoxonase 1 activity in newly diagnosed hypertensive patients. Clin Exp Hypertens. 2016; 38(8): 680-685. https://doi.org/10.1080/10641963.2016.1200602
[14] Narayana K, D'Souza UJ, Seetharama Rao KP. Ribavirin-induced sperm shape abnormalities in Wistar rat. Mutat Res. 2002; 513(1-2): 193-196. http://doi.org/10.1016/s1383-5718(01)00308-4
[15] Kanno TYN, Sensiate LA, de Paula NA, Salles MJS. Toxic effects of different doses of cyclophosphamide on the reproductive parameters of male mice. Braz J Pharm Sci. 2009; 45: 313-319. https://doi.org/10.1590/S1984-82502009000200017
[16] Türk G, Ceribaşi AO, Sakin F, Sönmez M, Ateşşahin A. Antiperoxidative and anti-apoptotic effects of lycopene and ellagic acid on cyclophosphamide-induced testicular lipid peroxidation and apoptosis. Reprod Fertil Dev. 2010; 22(4): 587-596. http://doi.org/10.1071/RD09078
[17] Fukushima T, Yamamoto T, Kikkawa R, Hamada Y, Komiyama M, Mori C, Horii I. Effects of male reproductive toxicants on gene expression in rat testes. J Toxicol Sci. 2005; 30(3): 195-206. http://doi.org/10.2131/jts.30.195
[18] Saxena AK, Kumar A. Effect of cyclophosphamide on testis- Protein profile study. In: Saxena AK, Kumar A. (Eds). Fish analysis for drug and chemicals mediated cellular toxicity. Springer Briefs in Applied Sciences and Technology, Springer, Singapore, 2020, pp:25-42.
[19] Sallam AO, Rizk HA, Emam MA, Fad SE, Abdelhiee EY, Khater H, Elkomy A, Aboubakr M. The ameliorative efects of L-carnitine against cisplatin-induced gonadal toxicity in rats. Pak Vet J. 2021; 41: 147–151. https://doi.org/10.29261/pakvetj/2020.082
[20] Ganguly R, Kumar R, Pandey AK. Baicalin provides protection against fluoxetine-induced hepatotoxicity by modulation of oxidative stress and inflammation. World J Hepatol. 2022; 14(4): 729-743. http://doi.org/10.4254/wjh.v14.i4.729
[21] Wu Y, Wang F, Fan L, Zhang W, Wang T, Du Y, Bai X. Baicalin alleviates atherosclerosis by relieving oxidative stress and inflammatory responses via inactivating the NF-κB and p38 MAPK signaling pathways. Biomed Pharmacother. 2018; 97: 1673-1679. http://doi.org/10.1016/j.biopha.2017.12.024
[22] Du G, Han G, Zhang S, Lin H, Wu H, Wang M, Ji L, Lu L, Yu L, Liang W. Baicalin suppresses lung carcinoma and lung metastasis by SOD mimic and HIF-1alpha inhibition. Eur J Pharmacol. 2010; 630(1-3): 121-130. http://doi.org/10.1016/j.ejphar.2009.12.014
[23] Alkhalaf MI, Alansari WS, Alshubaily FA, Alnajeebi AM, Eskandrani AA, Tashkandi MA, Babteen NA. Chemoprotective effects of inositol hexaphosphate against cyclophosphamide-induced testicular damage in rats. Sci Rep. 2020; 10(1): 12599. https://doi.org/10.1038/s41598-020-68608-9
[24] Torabi F, Malekzadeh Shafaroudi M, Rezaei N. Combined protective effect of zinc oxide nanoparticles and melatonin on cyclophosphamide-induced toxicity in testicular histology and sperm parameters in adult Wistar rats. Int J Reprod Biomed. 2017; 15(7): 403-412.
[25] Hosseini A, Zare S, Borzouei Z, Ghaderi Pakdel F. Cyclophosphamide-induced testicular toxicity ameliorate by American ginseng treatment: An experimental study. Int J Reprod Biomed. 2018; 16(11): 711-718.
[26] Ghosh D, Das UB, Misro M. Protective role of alpha-tocopherol-succinate (provitamin-E) in cyclophosphamide induced testicular gametogenic and steroidogenic disorders: a correlative approach to oxidative stress. Free Radic Res. 2002; 36(11): 1209-1218. https://doi.org/10.1080/1071576021000016472
[27] Wallace EM, Groome NP, Riley SC, Parker AC, Wu FC. Effects of chemotherapy-induced testicular damage on inhibin, gonadotropin, and testosterone secretion: a prospective longitudinal study. J Clin Endocrinol Metab. 1997; 82(9): 3111-3115. https://doi.org/10.1210/jcem.82.9.4238
[28] Adana MY, Imam A, Bello AA, Sunmonu OE, Alege EP, Onigbolabi OG, Ajao MS. Oral thymoquinone modulates cyclophosphamide-induced testicular toxicity in adolescent Wistar rats. Andrologia. 2022; 54(4): e14368. https://doi.org/10.1111/and.14368
[29] Zhu Y, Fu Y, Lin H. Baicalin inhibits renal cell apoptosis and protects against acute kidney injury in pediatric sepsis. Med Sci Monit. 2016; 22: 5109-5115. http://doi.org/10.12659/msm.899061
[30] Zhao H, Li C, Li L, Liu J, Gao Y, Mu K, Chen D, Lu A, Ren Y, Li Z. Baicalin alleviates bleomycin induced pulmonary fibrosis and fibroblast proliferation in rats via the PI3K/AKT signaling pathway. Mol Med Rep. 2020; 21(6): 2321-2334. https://doi.org/10.3892/mmr.2020.11046
[31] Shi L, Zhang S, Huang Z, Hu F, Zhang T, Wei M, Bai Q, Lu B, Ji L. Baicalin promotes liver regeneration after acetaminophen-induced liver injury by inducing NLRP3 inflammasome activation. Free Radic Biol Med. 2020; 160: 163-177. http://doi.org/10.1016/j.freeradbiomed.2020.05.012
[32] Wang Y. Epididymal sperm count. Curr Protoc Toxicol. 2003;Chapter 16:Unit16.6. https://doi.org/10.1002/0471140856.tx1606s14
[33] Filler R. Methods for evaluation of rat epididymal sperm morphology. In: Chapin RE, Heindel JH (Eds). Methods in Toxicology: Male Reproductive Toxicology. Academic Press, San Diego, CA, 1993, pp: 334–343.
[34] Köroğlu KM, Çevik Ö, Şener G, Ercan F. Apocynin alleviates cisplatin-induced testicular cytotoxicity by regulating oxidative stress and apoptosis in rats. Andrologia. 2019; 51(4): e13227. https://doi.org/10.1111/and.13227
[35] Sziva RE, Ács J, Tőkés AM, Korsós-Novák Á, Nádasy GL, Ács N, Horváth PG, Szabó A, Ke H, Horváth EM, Kopa Z, Várbíró S. Accurate quantitative histomorphometric-mathematical image analysis methodology of rodent testicular tissue and its possible future research perspectives in andrology and reproductive medicine. Life (Basel). 2022; 12(2): 189. http://doi.org/10.3390/life12020189
[36] Gozen A, Demiryurek S, Taskin A, Ciralik H, Bilinc H, Kara S, Aydin A, Aksoy N, Ceylan H. Protective activity of ischemic preconditioning on rat testicular ischemia: Effects of Y-27632 and 5-hydroxydecanoic acid. J Pediatr Surg. 2013; 48(7): 1565-1572. https://doi.org/10.1016/j.jpedsurg.2012.10.074
[37] Oktay Ş, Alev B, Koc Ozturk L, Tunali S, Demirel S, Emekli Alturfan E, Tunali-Akbay T, Akyuz S, Yanardag R, Yarat A. Edaravone ameliorates valproate-induced gingival toxicity by reducing oxidative stress, inflammation and tissue damage. Marmara Pharm J. 2016; 20(3): 243-251. https://doi.org/10.12991/mpj.20162096267.

Details

Primary Language

English

Subjects

Medical Pharmacology

Journal Section

Research Article

Authors

Gülseren Altay Aznavur ^* This is me
0000-0003-0873-2153
Türkiye

Doç.dr. Şehkar Oktay
Türkiye

Esin Ak
0000-0002-3467-7808
Türkiye

Publication Date

June 28, 2025

Submission Date

October 11, 2023

Acceptance Date

December 15, 2023

Published in Issue

Year 2024 Volume: 28 Number: 5

IZ

https://izlik.org/JA88SL45MG

Cite

RIS / Bibtex

APA

Altay Aznavur, G., Oktay, D. Ş., & Ak, E. (2025). Protective effect of baicalin on cyclophosphamide-induced oxidative stress and morphologic damage in testis tissue. Journal of Research in Pharmacy, 28(5), 1550-1561. https://izlik.org/JA88SL45MG

AMA

1.Altay Aznavur G, Oktay DŞ, Ak E. Protective effect of baicalin on cyclophosphamide-induced oxidative stress and morphologic damage in testis tissue. J. Res. Pharm. 2025;28(5):1550-1561. https://izlik.org/JA88SL45MG

Chicago

Altay Aznavur, Gülseren, Doç.dr. Şehkar Oktay, and Esin Ak. 2025. “Protective Effect of Baicalin on Cyclophosphamide-Induced Oxidative Stress and Morphologic Damage in Testis Tissue”. Journal of Research in Pharmacy 28 (5): 1550-61. https://izlik.org/JA88SL45MG.

EndNote

Altay Aznavur G, Oktay DŞ, Ak E (July 1, 2025) Protective effect of baicalin on cyclophosphamide-induced oxidative stress and morphologic damage in testis tissue. Journal of Research in Pharmacy 28 5 1550–1561.

IEEE

[1]G. Altay Aznavur, D. Ş. Oktay, and E. Ak, “Protective effect of baicalin on cyclophosphamide-induced oxidative stress and morphologic damage in testis tissue”, J. Res. Pharm., vol. 28, no. 5, pp. 1550–1561, July 2025, [Online]. Available: https://izlik.org/JA88SL45MG

ISNAD

Altay Aznavur, Gülseren - Oktay, Doç.dr. Şehkar - Ak, Esin. “Protective Effect of Baicalin on Cyclophosphamide-Induced Oxidative Stress and Morphologic Damage in Testis Tissue”. Journal of Research in Pharmacy 28/5 (July 1, 2025): 1550-1561. https://izlik.org/JA88SL45MG.

JAMA

1.Altay Aznavur G, Oktay DŞ, Ak E. Protective effect of baicalin on cyclophosphamide-induced oxidative stress and morphologic damage in testis tissue. J. Res. Pharm. 2025;28:1550–1561.

MLA

Altay Aznavur, Gülseren, et al. “Protective Effect of Baicalin on Cyclophosphamide-Induced Oxidative Stress and Morphologic Damage in Testis Tissue”. Journal of Research in Pharmacy, vol. 28, no. 5, July 2025, pp. 1550-61, https://izlik.org/JA88SL45MG.

Vancouver

1.Gülseren Altay Aznavur, Doç.dr. Şehkar Oktay, Esin Ak. Protective effect of baicalin on cyclophosphamide-induced oxidative stress and morphologic damage in testis tissue. J. Res. Pharm. [Internet]. 2025 Jul. 1;28(5):1550-61. Available from: https://izlik.org/JA88SL45MG