Protective effects of dried Ficus carica L. fruit against cisplatin-induced reprotoxicity in male rats evaluated by high-frequency ultrasound

Authors

  • Moufida Lounis University of Oum El Bouaghi, Faculty of Exact Sciences and Nature and Life Sciences, Department of Nature and Life Sciences, Laboratory of Natural Substances, Biomolecules and Biotechnological Applications, 04000 Oum El Bouaghi (DZ) https://orcid.org/0009-0003-0333-0240
  • Djahida Mahdi 1) University of Oum El Bouaghi, Faculty of Exact Sciences and Nature and Life Sciences, Department of Nature and Life Sciences, 04000 Oum El Bouaghi; 2) Badji Mokhtar University, Faculty of Sciences, Department of Biology, Laboratory of Animal Eco-Physiology, 23000 Annaba (DZ) https://orcid.org/0000-0001-7009-2340
  • Asma Saihia University of Oum El Bouaghi, Faculty of Exact Sciences and Nature and Life Sciences, Department of Nature and Life Sciences, 04000 Oum El Bouaghi (DZ) https://orcid.org/0009-0008-5432-2028
  • Adel Aissi University of Batna, Institute of Veterinary Sciences and Agricultural Sciences, Department of Veterinary Sciences, Veterinary Surgery and Imaging Service, 05000 Batna (DZ) https://orcid.org/0009-0000-1176-4688
  • Asma Berkani University of Oum El Bouaghi, Faculty of Exact Sciences and Nature and Life Sciences, Department of Nature and Life Sciences, 04000 Oum El Bouaghi (DZ) https://orcid.org/0000-0003-3730-3112
  • Yahia Khelef University of El Oued, Faculty of Nature and Life Sciences, Department of Cellular and Molecular Biology, Laboratory of Biology, Environment and Health (LBEH), 39000 El Oued (DZ) https://orcid.org/0000-0002-9255-3854

DOI:

https://doi.org/10.55779/nsb18212864

Keywords:

cisplatin, Ficus carica L., high-frequency ultrasound, male reproductive toxicity, oxidative stress, sperm parameters, testicular histology

Abstract

Cisplatin (Cis) is an effective chemotherapeutic agent, but its clinical use is limited by adverse effects on the testes and male reproductive function. This study evaluated, for the first time, the protective effect of dried Ficus carica L. fruit (F) against Cis-induced reprotoxicity in male rats using high-frequency ultrasound (HFUS), supported by hormonal, sperm, oxidative stress, anatomical, histological, heatmap, and principal component analyses. Twenty-four adult male rats were assigned to four groups: Control (C), F (1 g kg⁻¹day⁻¹), Cis (3.5 mg kg⁻¹week⁻¹, intraperitoneally, three times), and FCis. In Cis-treated rats, HFUS revealed increased testis length, reduced width, anechoic fluid regions, loss of parenchymal homogeneity, and disruption of the tunica albuginea. These alterations were associated with reduced body weight, testosterone, follicle-stimulating hormone, luteinizing hormone, sperm count, sperm motility, and glutathione, together with increased relative testicular weight and malondialdehyde levels. Anatomical and histological examinations confirmed inflammation, haemorrhage, congestion, germ-cell apoptosis, fibrosis, and deformation of the seminiferous tubules. Heatmap analysis showed positive correlations among hormone levels, sperm parameters, and glutathione, and negative correlations with malondialdehyde. Principal component analysis highlighted testis length and width as sensitive indicators of Cis toxicity. Co-treatment with Ficus carica L. markedly alleviated these adverse effects. These findings suggest that HFUS is a valuable non-invasive approach for assessing Cis-induced reprotoxicity in rats and that dried Ficus carica L. fruit may provide protective benefits.

Metrics

Metrics Loading ...

References

Abdel-Latif R, Fathy M, Anwar HA, Naseem M, Dandekar T, Othman EM (2022). Cisplatin-induced reproductive toxicity and oxidative stress: ameliorative effect of kinetin. Antioxidants, 11(5): 863. https://doi.org/10.3390/antiox11050863

Abdelhiee EY, Fadl SE, Ashry A, Eid MM, Eltholoth MM, Abdelghany NA, et al. (2025). Harnessing Nature: The Role of Medicinal Plants in Alleviating Cisplatin Toxicity. Pakistan Veterinary Journal, 45(1): 73–83. https://doi.org/10.29261/pakvetj/2025.136

Adelakun SA, Akintunde OW, Ogunlade B, Adeyeluwa BE (2023). Histochemical and histomorphological evidence of the modulating role of 1-isothiocyanate-4-methyl sulfonyl butane on cisplatin-induced testicular-pituitary axis degeneration and cholesterol homeostasis in male Sprague-Dawley rats. Morphologie, 107(356): 80–98. https://doi.org/10.1016/j.morpho.2022.05.002

Ain NU, Khan RA, Mirza T, Fayyaz T (2022). The effects of Ficus carica on male and female reproductive capabilities in rats. Evidence-Based Complementary and Alternative Medicine, 2022: 1799431. https://doi.org/10.1155/2022/1799431

Ali SH, Elsyade RH, Abdel Wahab KH, AL Badawi MH (2024). The protective role of L-carnitine against cisplatin-induced testicular toxicity in the adult albino rat. Egyptian Journal of Histology, 47(1): 151–165. https://doi.org/10.21608/ejh.2022.172815.1803

Aly HAA, Eid BG (2020). Cisplatin-induced testicular damage through mitochondria-mediated apoptosis, inflammation and oxidative stress in rats: impact of resveratrol. Endocrine Journal, 67(9): 969–980. https://doi.org/10.1507/endocrj.EJ20-0149

Arkalı G, Acısu TC, Ekmen EG, Sağıroğlu M, Koçyiğit FB, Çay M, et al. (2025). The effect of kisspeptin-10 on cisplatin-induced testicular oxidative stress. Balıkesir Sağlık Bilimleri Dergisi, 14(1): 184–191. https://doi.org/10.53424/balikesirsbd.1609836

Aryal S, Baniya MK, Danekhu K, Kunwar P, Gurung R, Koirala N (2019). Total phenolic content, flavonoid content and antioxidant potential of wild vegetables from Western Nepal. Plants, 8(4): 96. https://doi.org/10.3390/plants8040096

Ateşşahin A, Şahna E, Türk G, Çeribaşi AO, Yılmaz S, Yüce A, et al. (2006). Chemoprotective effect of melatonin against cisplatin-induced testicular toxicity in rats. Journal of Pineal Research, 41(1): 21–27. https://doi.org/10.1111/j.1600-079X.2006.00327.x

Ayala A, Muñoz MF, Argüelles S (2014). Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxidative Medicine and Cellular Longevity, 2014(1): 360438. https://doi.org/10.1155/2014/360438

Ayuso M, Carpena M, Taofiq O, Albuquerque TG, Simal-Gandara J, Oliveira MBPP, et al. (2022). Fig (Ficus carica L.) and its by-products: a decade evidence of their health-promoting benefits towards the development of novel food formulations. Trends in Food Science and Technology, 127(6): 1–13. https://doi.org/10.1016/j.tifs.2022.06.010

Badr AM, Aloyouni S, Mahran Y, Henidi H, Elmongy EI, Alsharif HM, et al. (2025). Thymol preserves spermatogenesis and androgen production in cisplatin-induced testicular toxicity by modulating ferritinophagy, oxidative stress, and the Keap1/Nrf2/HO-1 pathway. Biomolecules, 15(9): 1277. https://doi.org/10.3390/biom15091277

Banzato T, Bellini L, Contiero B, Martin A, Balikçi S, Zotti A (2014). Abdominal anatomic features and reference values determined by use of ultrasonography in healthy common rats (Rattus norvegicus). American Journal of Veterinary Research, 75(1): 67–76. https://doi.org/10.2460/ajvr.75.1.67

Bey MB, Louaileche H (2015). A comparative study of phytochemical profile and in vitro antioxidant activities of dark and light dried fig (Ficus carica L.) varieties. Journal of Phytopharmacology, 4(1): 41–48. https://doi.org/10.31254/phyto.2015.4108

Beytur A, Ciftci O, Oguz F, Oguzturk H, Yılmaz F (2012). Montelukast attenuates side effects of cisplatin including testicular, spermatological, and hormonal damage in male rats. Cancer Chemotherapy and Pharmacology, 69(1): 207–213. https://doi.org/10.1007/s00280-011-1692-y

Bittencourt J (2018). The power of carbohydrates, proteins, and lipids: how to make wise choices in diet and nutrition. CreateSpace Independent Publishing Platform.

Elghareeb MM, Elshopakey GE, Hendam BM, Rezk S, Lashen S (2021). Synergistic effects of Ficus carica extract and extra virgin olive oil against oxidative injury, cytokine liberation, and inflammation mediated by 5-fluorouracil in cardiac and renal tissues of male albino rats. Environmental Science and Pollution Research, 28(4): 4558–4572. https://doi.org/10.1007/s11356-020-10778-0

Elmorsy EA, Saber S, Hamad RS, Abdel-Reheim MA, El-Kott AF, AlShehri MA, et al. (2024). Advances in understanding cisplatin-induced toxicity: molecular mechanisms and protective strategies. European Journal of Pharmaceutical Sciences, 203: 106939. https://doi.org/10.1016/j.ejps.2024.106939

Gafar AA, Khalifa MA, Elshaer F (2018). Protective and therapeutic effects of olive oil and Ficus carica on the histological and cytological injuries of liver and kidney in irradiated male albino rats. Al Azhar Bulletin of Science, 29(2 C):69–88. https://doi.org/10.21608/ABSB.2018.33820

Ghanti A, Shankar KMK, Asokan YV, GVR, Naaram NM, RHK (2024). Relation between serum hormones and semen parameters in sub-fertile males: is 17-hydroxyprogesterone really a game changer? International Journal of Reproduction, Contraception, Obstetrics and Gynecology, 13(4): 862–867. https://doi.org/10.18203/2320-1770.ijrcog20240690

Harikrishnan R, Abhilash PA, Das SS, Prathibha P, Rejitha S, John F, et al. (2013). Protective effect of ascorbic acid against ethanol-induced reproductive toxicity in male guinea pigs. British Journal of Nutrition, 110(4): 689–698. https://doi.org/10.1017/S0007114512005739

Hokmabadi A, Ranjbar E, Alipour F, Ebrahimzadeh-Bideskan A, Afshari JT, Rezaei MM, et al. (2024). Protective effect of dental pulp stem cells’ conditioned medium against cisplatin-induced testicular damage in rats. Toxicology, 504: 153788. https://doi.org/10.1016/j.tox.2024.153788

Ilbey YO, Ozbek E, Simsek A, Cekmen MB (2009). Potential effect of melatonin in cyclophosphamide and cisplatin-induced testicular damage in rats. Fertility and Sterility, 92(1): 318–324. https://doi.org/10.1016/j.fertnstert.2008.07.1758

Issaoui M, Delgado AM, Caruso G, Micali M, Barbera M, Atrous H, et al. (2021). Phenols, flavors, and the Mediterranean diet. Journal of AOAC International, 103(4): 915–924. https://doi.org/10.1093/JAOCINT/QSZ018

Kaya K, Ciftci O, Cetin A, Doğan H, Başak N (2015). Hesperidin protects testicular and spermatological damages induced by cisplatin in rats. Andrologia, 47(7): 793–800. https://doi.org/10.1111/and.12332

Kebal L, Pokajewicz K, Djebli N, Mostefa N, Poliwoda A, Wieczorek PP (2022). HPLC-DAD profile of phenolic compounds and in vitro antioxidant activity of Ficus carica L. fruits from two Algerian varieties. Biomedicine and Pharmacotherapy, 155(9): 113738. https://doi.org/10.1016/j.biopha.2022.113738

Keshta AT, Fathallah AM, Attia YA, Salem EA, Watad SH (2023). Ameliorative effect of selenium nanoparticles on testicular toxicity induced by cisplatin in adult male rats. Food and Chemical Toxicology, 179(7): 113979. https://doi.org/10.1016/j.fct.2023.113979

Khalaji N, Namyari M, Rasmi Y, Pourjabali M, Chodari L (2018). Protective effect of curcumin on fertility of rats after exposure to compact fluorescent lamps: An experimental study. International Journal of Reproductive BioMedicine, 16(7): 447. https://doi.org/10.29252/ijrm.16.7.447

Kiralan M, Ketenoglu O, Kiralan SS, Yilmaz FM (2023). Composition and functional properties of fig (Ficus carica) phenolics. In: Fig (Ficus carica): Production, Processing, and Properties. Springer, 369–394. https://doi.org/10.1007/978-3-031-16493-4_17

Lee S, Kim H, Lee MH, Eun Y, Hwang JY (2025). High-frequency ultrasound techniques for measurement of cell and tissue mechanics. In: Integration and Bridging of Multiscale Bioengineering Designs and Tissue Biomechanics. Springer, 521–537. https://doi.org/10.1007/978-3-031-81743-4_17

Lin Y, Lu W, Li G, Mao L, Ouyang L, Zhu Z, et al. (2024). Non-invasive evaluation of testicular torsion using ultrasound shear wave elastography: an experimental study. Ultrasonography, 43(3):98–109. https://doi.org/10.14366/usg.23171

Lopes-Ferreira JV, Matos JEM, Dias FCR, Siervo G, Gomes MLM (2025). Protective effects of phenolic phytochemicals on male fertility: a narrative review. Brazilian Journal of Biology, 85: e288879. https://doi.org/10.1590/1519-6984.288879

Lovell EAK, Hosking SL, Groome HM, Moldenhauer LM, Robertson SA, Gatford KL, et al. (2024). Effects of exercise on vascular remodelling and fetal growth in uncomplicated and abortion-prone mouse pregnancies. Scientific Reports, 14(1): 1–16. https://doi.org/10.1038/s41598-024-83329-z

Ly C, Yockell-Lelievre J, Ferraro ZM, Arnason JT, Ferrier J, Gruslin A (2015). The effects of dietary polyphenols on reproductive health and early development. Human Reproduction Update, 21(2): 228–248. https://doi.org/10.1093/humupd/dmu058

Mahanem MN, Puvaratnesh S, Umarqayum A, Nadia SA (2024). Pro-fertility effect of Ficus carica fruit extract in streptozotocin-induced male rats. Asian Pacific Journal of Reproduction, 13(1): 34–41. https://doi.org/10.4103/apjr.apjr_133_23

Makled MN, Said E (2021). Tranilast abrogates cisplatin-induced testicular and epididymal injuries: an insight into its modulatory impact on apoptosis/proliferation. Journal of Biochemical and Molecular Toxicology, 35(8): e22817. https://doi.org/10.1002/jbt.22817

Martin LJ, Touaibia M (2020). Improvement of testicular steroidogenesis using flavonoids and isoflavonoids for prevention of late-onset male hypogonadism. Antioxidants, 9(3): 237. https://doi.org/10.3390/antiox9030237

Meziant L, Bachir-Bey M, Boutiche M, Gali L, Ikhlef A, Louaileche H (2022). Assessment of flavonoid-rich extracts from dark peels of Ficus carica L. fruits for cosmeceutical and antimicrobial applications. Traditional Medicine Research, 7(6): 1–12. https://doi.org/10.53388/TMR20220313002

Mircea CN, Lujan ME, Jaiswal RS, Singh J, Adams GP, Pierson RA (2009). Ovarian imaging in the mouse using ultrasound biomicroscopy (UBM): a validation study. Reproduction, Fertility and Development, 21(4): 579–586. https://doi.org/10.1071/RD08295

Moradi M, Hashemian MA, Faramarzi A, Goodarzi N, Hashemian AH, Cheraghi H, et al. (2024). Therapeutic effect of sodium alginate on bleomycin, etoposide and cisplatin (BEP)-induced reproductive toxicity by inhibiting nitro-oxidative stress, inflammation and apoptosis. Scientific Reports, 14(1): 1–15. https://doi.org/10.1038/s41598-024-52010-w

Nna VU, Ujah GA, Suleiman JB, Mohamed M, Nwokocha C, Akpan TJ, et al. (2020). Tert-butylhydroquinone preserve testicular steroidogenesis and spermatogenesis in cisplatin-intoxicated rats by targeting oxidative stress, inflammation and apoptosis. Toxicology, 441(6): 152528. https://doi.org/10.1016/j.tox.2020.152528

Ohkawa H, Ohishi N, Yagi K (1979). Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry, 95(2): 351–358. https://doi.org/10.1016/0003-2697(79)90738-3

World Health Organization (1999). WHO laboratory manual for the examination of human semen and sperm-cervical mucus interaction. Cambridge: Cambridge University Press.

Othman EM, Habib HA, Zahran ME, Amin A (2023). Mechanistic protective effect of cilostazol in cisplatin-induced testicular damage via regulation of oxidative stress and TNF-α/NF-κB/caspase-3 pathways. International Journal of Molecular Sciences, 24(16): 12651. https://doi.org/10.3390/ijms241612651

Pal I (2020). A comprehensive review on Ficus carica L.: an unexplored medicinal plant. International Journal of Advanced Research, 8(12): 876–881. https://doi.org/10.21474/ijar01/12227

Rahimi A, Asadi F, Rezghi M, Kazemi S, Soorani F, Memariani Z (2022). Natural products against cisplatin-induced male reproductive toxicity: a comprehensive review. Journal of Biochemical and Molecular Toxicology, 36(3): e22970. https://doi.org/10.1002/jbt.22970

Ramadan MF (2023). Fig (Ficus carica): production, processing, and properties. In: Fig (Ficus carica): Production, Processing, and Properties. Springer. https://doi.org/10.1007/978-3-031-16493-4

Rose O, Croonenberg T, Clemens S, Hinteregger T, Eppacher S, Huber-Cantonati P, et al. (2024). Cisplatin-induced hearing loss, oxidative stress, and antioxidants as a therapeutic strategy-A state-of-the-art review. Antioxidants, 13(12): 1578. https://doi.org/10.3390/antiox13121578

Şahmelikoğlu AG, Başaloğlu H, Demirci B (2024). Effect of silymarin on testicular morphology and sperm numbers in cisplatin damage. Anatomy, 18:1–10. https://doi.org/10.2399/ana.23.056

Salah S, Nabil N, El H, Hosni D (2020). The defensive role of taurine against gonadotoxicity and testicular apoptosis effects induced by cisplatin in rats. Journal of Infection and Chemotherapy, 26(1): 51–57. https://doi.org/10.1016/j.jiac.2019.07.004

Shafiey SI, Abo-Saif AA, Abo-Youssef AM, Mohamed WR (2022). Protective effects of rivaroxaban against cisplatin-induced testicular damage in rats: impact on oxidative stress, coagulation, and p-NF-κB/VCAM-1 signaling. Food and Chemical Toxicology, 169(6): 113419. https://doi.org/10.1016/j.fct.2022.113419

Soni N, Mehta S, Satpathy G, Gupta RK (2014). Estimation of nutritional, phytochemical, antioxidant and antibacterial activity of dried fig (Ficus carica). Journal of Pharmacognosy and Phytochemistry, 3(2): 158–165.

Suvarna SK, Layton C, Bancroft JD (2012). Theory and practice of histological techniques. Elsevier Health Sciences.

Turan A, Celik I, Bati B (2018). The healing properties of dried figs (Ficus carica L.) against oxidative stress caused by ethyl alcohol in rats. Bulletin of Environment, Pharmacology and Life Sciences, 7: 30–36.

Tvrda E, Peer R, Sikka SC, Agarwal A (2015). Iron and copper in male reproduction: a double-edged sword. Journal of Assisted Reproduction and Genetics, 32(1): 3–16. https://doi.org/10.1007/s10815-014-0344-7

Weckbecker G, Cory JG (1988). Ribonucleotide reductase activity and growth of glutathione-depleted mouse leukemia L1210 cells in vitro. Cancer Letters, 40(3): 257–264. https://doi.org/10.1016/0304-3835(88)90084-0

Wei YS, Chen YL, Li WY, Yang YY, Lin SJ, Wu CH, et al. (2023). Antioxidant nanoparticles restore cisplatin-induced male fertility defects by promoting MDC1–53BP1-associated non-homologous DNA repair mechanism and sperm intracellular calcium influx. International Journal of Nanomedicine, 18(8): 4313–4327. https://doi.org/10.2147/IJN.S408623

Yousef MI, Abdallah GA, Kamel KI (2003). Effect of ascorbic acid and vitamin E supplementation on semen quality and biochemical parameters of male rabbits. Animal Reproduction Science, 76(1–2): 99–111. https://doi.org/10.1016/S0378-4320(02)00226-9

Zhang X, Qian J, Wei B, Zhang B (2025). Flavonoids as modulators of Nrf2 signaling pathway in alleviating cisplatin-induced organ toxicity. Yangtze Medicine, 9(1): 52–77. https://doi.org/10.4236/ym.2025.91006

Zhang X, Tang Y, Lu G, Gu J (2023). Pharmacological activity of flavonoid quercetin and its therapeutic potential in testicular injury. Nutrients, 15(9): 2231. https://doi.org/10.3390/nu15092231

Downloads

Published

2026-06-02

How to Cite

Lounis, M., Mahdi, D., Saihia, A., Aissi, A., Berkani, A., & Khelef, Y. (2026). Protective effects of dried Ficus carica L. fruit against cisplatin-induced reprotoxicity in male rats evaluated by high-frequency ultrasound. Notulae Scientia Biologicae, 18(2), 12864. https://doi.org/10.55779/nsb18212864

Issue

Section

Research Articles
CITATION
DOI: 10.55779/nsb18212864