Citrullus lanatus (Thunb) improves an antidepressant-induced impaired fertility in depressed male mouse model
Abstract
Synthetic antidepressants are used in the treatment of mental illness, however due to their side effects people are orienting towards the herbal product as an alternative therapy. The present study therefore, explores the role of C. lanatus (CL) seed extract in evaluating the fluoxetine-induced impaired sperm functions, and fertility of the depressed mice. Adult Swiss strain male mice were separated into six group. Every group contains six animals. Group I received vehicle-treated negative control while Groups II, III, IV, V and VI administered with reserpine (RES) at dose of 0.75 mg/kgBW/day, for 14 days to induce depression, fluoxetine (FLX) at the dose of 40 mg/kgBW/day in depressed mice (positive control) for 28 days, CL seed extract (300 mg/kgBW/day) only, in normal mice, and co-administrations of FLX (40 mg/kgBW/day) with low and high doses of seed extract of CL (150 mg/kgBW/day and 300 mg/kgBW/day) respectively, in the depressed mice for the same duration. Mice of Gr. II and Gr. IV did not alter the epididymal sperm parameters and fertility. However, significant alterations were observed in such parameters in the mice of Gr. III. Partial to complete restorations were noticed in such parameters in Gr. V and VI, as compared to the positive control of Gr. III. The findings suggest that CL seed extract may emerge as a potential herbal remedy to impaired fertility which could be of therapeutic drug in future.
Keywords:
Sperm parameters, Fertility, Fluoxetine, Citrullus lanatusDOI
https://doi.org/10.25004/IJPSDR.2024.160605References
Institute of Health Metrics and Evaluation (2023). Global health data exchange (GHDx).
Mago R, Tripathi N, Andrade C. Cardiovascular adverse effects of newer antidepressants. Expert review of neurotherapeutics. 2014; 14:539-51. Available from: doi.org/10.1586/14737175.2014.908709
Mihanović M, Restek-Petrović B, Bodor D, Molnar S, Orešković A, Presečki P. Suicidality and side effects of antidepressants and antipsychotics. Psychiatria Danubina. 2010; 22: 79-84.
Wang Z, Li H, Kang Y, Liu Y, Shan L, Wang F. Risks of digestive system side-effects of selective serotonin reuptake inhibitors in patients with depression: A network meta-analysis. Therapeutics and Clinical Risk Management. 2022; 18:799-812. Available from:doi.org/10.2147/TCRM.S363404.
Milosavljević JZ, Milosavljević MN, Arsenijević PS, Milentijević MN, Stefanović SM. The effects of selective serotonin reuptake inhibitors on male and female fertility: a brief literature review. International Journal of Psychiatry in Clinical Practice. 2022; 26:43-49. Available from: doi.org/10.1080/13651501.2021.1872647
Motwani S, Hukumchand A, Karia S, Sonavane S, Desousa A. Sexual Dysfunction with Antidepressants: A Clinical Review. A Clinical Review. Indian Journal of Private Psychiatry. 2023; 17:78-82. Available from: 10.5005/jp-journals-10067-0143
Silva JV, Lins AM, Amorim J, Pinto CF, Deiró TB, Oliveira JR, Peixoto CA, Manhães-de-Castro R. Neonatal administration of fluoxetine decreased final sertoli cell number in Wistar rats. International Journal of Morphology. 2008; 26:51-62. Available from: doi.org/10.4067/s0717-95022008000100009
Sakr HF, Abbas AM, Elsamanoudy AZ, Ghoneim FM. Effect of fluoxetine and resveratrol on testicular functions and oxidative stress in a rat model of chronic mild stress-induced depression. Journal of Physiology and Pharmacology. 2015; 66:515-27.
Camara ML, Almeida TB, de Santi F, Rodrigues BM, Cerri PS, Beltrame FL, Sasso-Cerri E. Fluoxetine-induced androgenic failure impairs the seminiferous tubules integrity and increases ubiquitin carboxyl-terminal hydrolase L1 (UCHL1): Possible androgenic control of UCHL1 in germ cell death?. Biomedecine and Pharmacotherapy. 2019; 109:1126-39. Available from: doi.org/10.1016/j.biopha.2018.10.034
Tang M, Ai Y, Zhu S, Song N, Xu X, Liang L, Rong B, Zheng X, Zhang L, He T. Antidepressant-like effect of essential oils from Citrus reticulata in reserpine-induced depressive mouse. Natural Product Communications. 2022; 17:1934578X221093916. Available from: doi.org/10.1177/1934578X221093
Kumar S, Tripathi A, Singh P. Antidepressant-Induced Testicular Alterations in the Normal and Depressed Mice. JSM Sexual Medicine. 2024; 8: 1126. Available from: doi.org/10.47739/2578-3718.sexualmedicine.1126
Alzahrani HA. Sister chromatid exchanges and sperm abnormalities produced by antidepressant drug fluoxetine in mouse treated in vivo. European Review for Medical & Pharmacological Sciences. 2012;16: 2154-2161.
Bataineh HN, Daradka T. Effects of long-term use of fluoxetine on fertility parameters in adult male rats. Neuroendocrinology Letters. 2007; 28(3):321-5.
Nantia EA, Moundipa PF, Monsees TK, Carreau S. Medicinal plants as potential male anti-infertility agents: a review. Andrologia. 2009; 19:148-58. Available from: doi.org/10.1007/s12610-009-0030-2
Chauhan NS, Sharma V, Dixit VK, Thakur M. A review on plants used for improvement of sexual performance and virility.
BioMed Research International. 2014; 2014:868062. Available from: doi.org/10.1155/2014/868062
Kumar Manikyam H. Chapter 11 Medicinal plants and alternative therapies for reproductive system health. In H. Ullah, A Rauf and M. Daglia (Ed.), Nutraceuticals: A Holistic Approach to Disease Prevention. Berlin, Boston: De Gruyter: 2024; p. 237-266. Available from: doi.org/10.1515/9783111317601-011
Hazra S, Banerjee R, Das BK, Ghosh AK, Banerjee TK, Hazra US, Mondal AC. Evaluation of antidepressant activity of Bacopa monnieri in rat: a study in animal model of depression. Drug Discovery. 2012; 2: 8-13. Available from: doi.org/10.1155/2014/868062
Patel SK, Singh S, Singh SK. Standardized extract of Bacopa monnieri (CDRI-08): Effect on germ cell dynamics and possible mechanisms of its beneficial action on spermatogenesis and sperm quality in male mice. Biochemical and Biophysical Research Communications. 2017;494: 34-41. Available from: doi.org/10.1016/j.bbrc.2017.10.089
Jafar SN, Mawlood KA. Protective role of pomegranate peel and piper longum fruit on the testicular function of thioacetamide-induced reproductive toxicity of male albino rats. Plant Archives. (09725210). 2010; 20: 2355-2362.
Sharma P, Parmar J, Verma P, Goyal PK. Radiation induced oxidative stress and its toxicity in testes of mice and their prevention by Tinospora cordifolia extract. Journal of Reproductive Health and Medicine. 2015; 1: 64-75. Available from: doi.org/10.1016/j.jrhm.2015.01.005
Sakr SA, Badawy GM. Effect of ginger (Zingiber officinale R.) on metiram-inhibited spermatogenesis and induced apoptosis in albino mice. Journal of Applied Pharmaceutical Science. 2011; 1: 131-136.
Durg S, Shivaram SB, Bavage S. Withania somnifera (Indian ginseng) in male infertility: An evidence-based systematic review and meta-analysis. Phytomedicine. 2018; 50:247-256. Available from: doi.org/10.1016/j.phymed.2017.11.011
Mojoyinola AO, Ishaya HB, Makena W, Jacob CB, Jonga UM, Anochie VC, Gadzama MN. Protective effect of ciprofloxacin-induced oxidative stress, testicular and hepatorenal injury by Citrullus lanatus L. (Watermelon) seeds in adult Wistar rats. South African Journal of Botany. 2023; 156: 365-375. Available from: doi.org/10.1016/j.sajb.2023.03.017
Gautam K, Kumar S, Srivastava S, Singh P. Pharmacological Properties of Citrullus lanatus. Perspective of Recent Advances in Medical Research. 2023; 6: 1-30. Available from: doi.org/10.9734/bpi/pramr/v6/4105B
Can ÖD, Özkay ÜD, Üçel Uİ. Anti-depressant-like effect of vitexin in BALB/c mice and evidence for the involvement of monoaminergic mechanisms. European Journal of Pharmacology. 2013; 699:250-7. Available from:doi.org/10.1016/j.ejphar.2012.10.017
Rafieian-Kopaei M, Movahedi M. Systematic review of premenstrual, postmenstrual and infertility disorders of Vitex agnus cactus. Electronic physician. 2017; 9:3685. Available from: doi.org/10.19082/3685
Chike CP, Dede EB, Oputah NP. Effect of Long-Term Administration of Citrullus Lanatus on Fertility Hormones of Male and Female Albino Rats. Nigerian Journal of General Practice. 2011; 9:25-33. Available from: doi.org/10.4314/njgp.v9i1.70674
Awaad EA, El Gamel AM. Effect of Citrullus Lanatus (watermelon) pulp and seeds extracts on fertility of experimental rats. Egyptian Journal of Nutrition. 2020; 35:1-31. Available from: doi.org/10.21608/enj.2020.144754
Odo RI, Uchendu CN, Okeke SE. Protective effects of Citrullus lanatus seed ethanol extract on aluminium chloride-induced testosterone, testicular and haematological changes in an experimental male rat model. In Veterinary Research Forum Faculty of Veterinary Medicine, Urmia University, Urmia, Iran. 2021; 12: p. 7. Available from: doi.org/10.30466/vrf.2020.104327.2480
Khaki A, Fathiazad F, Nouri M. Effects of watermelon seed extract (Citrullus vulgaris) on spermatogenesis in rat. International Journal of Women's Health and Reproduction Sciences. 2013; 1:99-104.
Godspower O, Williams N, Elochukwu N. Ameliorative Potential of Methanolic extract of Citrullus lanatus (Watermelon) Seeds on the Sperm parameters, testosterone level and testicular cytoarchitecture of male albino rats Induced with lead-acetate. British Journal of Pharmaceutical Research. 2015; 6:35-43. Available from: doi.org/10.9734/BJPR/2015/15358
Kolawole T, Adienbo O, Dapper V. Ameliorative effects of hydromethanolic extract of Citrullus lanatus (watermelon) rind on semen parameters, reproductive hormones and testicular oxidative status following nicotine administration in male Wistar rats. Nigerian Journal of Physiological Sciences. 2019; 34:83-90.
Kolawole AT, Dapper VD, Eziuzo CI. Effects of the methanolic extract of the rind of Citrullus lanatus (watermelon) on some erythrocyte parameters and indices of oxidative status in phenylhydrazine-treated male Wistar rats. Journal of African Association of Physiological Sciences. 2017; 5:22-8.
Kolawole TA, Dapper DV, Ojeka SO. Ameliorative effects of the methanolic extract of the rind of Citrullus lanatus on lead acetate induced toxicity on semen parameters and reproductive hormones of Male albino Wistar rats. European journal of medicinal plants. 2014; 4:1125-1137. Available from:10.9734/EJMP/2014/11011
Daramola OO, Oyeyemi WA, Beka FU, Ofutet EA. Protective effects of aqueous extract of Citrullus lanatus fruit on reproductive functions and antioxidant activities in arsenic-treated male wistar rats. African Journal of Biomedical Research. 2018; 21:65-72.
Adnaik RS, Gavarkar PS, Mohite SK, Magdum CS. Anti-depressant activity of ethanolic extract of Citrullus vulgaris seeds in experimentally induced depressed mice. Research Journal of Pharmacy and Technology. 2014; 7:660-2. Available from: 10.5958/0974-360X
Edition F Examination and processing of human semen. World Health [Internet]. 2010.
Wyrobek AJ, Bruce WR. Chemical induction of sperm abnormalities in mice. Proceedings of the National Academy of Sciences. 1975; 72:4425-9. Available from: doi.org/10.1073/pnas.72.11.4425
Zaneveld LJ, Polakoski KL. Collection and physical examination of the ejaculate. Techniques of human andrology. 1977; 1:147-72.
Narotsky MG, Brownie CF, Kavlock RJ. Critical period of carbon tetrachloride‐induced pregnancy loss in Fischer‐344 rats, with insights into the detection of resorption sites by ammonium sulphide staining. Teratology. 1997; 56:252-61. Available from: doi.org/10.1002/(SICI)1096-9926(199710)56:4<252::AID-TERA4>3.0.CO;2-0
Roboon J, Nudmamud‐Thanoi S, Thanoi S. Recovery effect of pre‐germinated brown rice on the alteration of sperm quality, testicular structure and androgen receptor expression in rat model of depression. Andrologia. 2017; 49: e12596. Available from: doi.org/10.1111/and.12596
Barbăroșie C, Agarwal A, Henkel R. Diagnostic value of advanced semen analysis in evaluation of male infertility. Andrologia. 2021; 53: e13625. Available from: doi.org/10.1111/and.13625
Nallella KP, Sharma RK, Aziz N, Agarwal A. Significance of sperm characteristics in the evaluation of male infertility. Fertility and Sterility. 2006; 85:629-34. Available from: doi.org/10.1016/j.fertnstert.2005.08.024
Shetty SD, Bairy LK. Effect of sorafenib on sperm count and sperm motility in male Swiss albino mice. Journal of Advanced Pharmaceutical Technology & Research. 2015; 6:165-9. Available from: doi.org/10.4103/2231-4040.165012
Pernoncini KV, Montagnini BG, de Góes ML, Garcia PC, Gerardin DC. Evaluation of reproductive toxicity in rats treated with triclosan. Reproductive Toxicology. 2018; 75:65-72. Available from: doi.org/10.1016/j.reprotox.2017.11.010
Raj S, Singh SS, Singh SP, Singh P. Evaluation of Triclosan-induced reproductive impairments in the accessory reproductive organs and sperm indices in the mice. Acta Histochemica. 2021; 123:151744. Available from: doi.org/10.1016/j.acthis.2021.151744
Tanga BM, Qamar AY, Raza S, Bang S, Fang X, Yoon K, Cho J. Semen evaluation: Methodological advancements in sperm quality-specific fertility assessment—A review. Animal Bioscience. 2021; 34:1253. Available from: doi.org/10.5713/ab.21.0072
Zrimšek P, Manafi ME. Evaluation of a new method and diagnostic test in semen analysis. Artificial insemination in farm animals. In Manafi ME (ed.). Rijeka, Croatia. 2011; p. 131-52. Available from: doi.org/10.5772/16798
Nørr L, Bennedsen B, Fedder J, Larsen ER. Use of selective serotonin reuptake inhibitors reduces fertility in men. Andrology. 2016; 4:389-94. Available from: doi.org/10.1111/andr.12184
Beeder LA, Samplaski MK. Effect of antidepressant medications on semen parameters and male fertility. International Journal of Urology. 2020; 27:39-46. Available from: doi.org/10.1111/iju.14111
Alsabhan JF, Almalag HM, Alnuaim LA, Albaker AB, Alaseem MM. Evaluating the Use of Selective Serotonin Reuptake Inhibitors (SSRIs) and Male Infertility: A Critical Retrospective Study. Journal of Clinical Medicine. 2024; 13:2129. Available from: 10.3390/jcm13072129
Fernandez-Fuertes B, Blanco-Fernandez A, Reid CJ, Meade KG, Fair S, Lonergan P. Removal of sialic acid from bull sperm decreases motility and mucus penetration ability but increases zona pellucida binding and polyspermic penetration in vitro. Reproduction. 2018; 155:481-92. Available from: doi.org/10.1530/REP-17-0429
Dutta S, Majzoub A, Agarwal A. Oxidative stress and sperm function: A systematic review on evaluation and management. Arab Journal of Urology . 2019;17: 87-97. Available from: doi.org/10.1080/2090598X.2019.1599624
Babaei A, Asadpour R, Mansouri K, Sabrivand A, Kazemi‐Darabadi S. Lycopene protects sperm from oxidative stress in the experimental varicocele model. Food Science and Nutrition. 2021; 9: 6806-6817. Available from: doi.org/10.1002/fsn3.2632
Rotimi DE, Asaleye RM. Impact of Watermelon (Citrallus lanatus) on Male Fertility. JBRA assisted reproduction. 2023; 27: 702-708. Available from: 10.5935/1518-0557.20220075.
Hotta Y, Shiota A, Kataoka T, Motonari M, Maeda Y, Morita M, Kimura K. Oral L‐citrulline supplementation improves erectile function and penile structure in castrated rats. International Journal of Urology. 2014; 21: 608-612. Available from: doi.org/10.1111/iju.12362
Ijaz MU, Tahir A, Ahmed H, Ashraf A, Ahmedah HT, Muntean L, Moga M, Irimie M. Chemoprotective effect of vitexin against cisplatin-induced biochemical, spermatological, steroidogenic, hormonal, apoptotic and histopathological damages in the testes of Sprague-Dawley rats. Saudi Pharmaceutical Journal. 2022; 30:519-26. Available from: doi.org/10.1016/j.jsps.2022.03.001
Wankeu-Nya M, Djeumeni ON, Nde Z, Tchamadeu MC, Kengne TI, Hatho TD, Koloko BL, Massoma LD, Dongmo AB, Moundipa FP, Watcho P. Aphrodisiac and androgenic effects of the aqueous extract of the roots of Vepris afzelii on cyproterone acetate-induced hypogonadism in rat. International Journal of Impotence Research. 2024; 29:1-0. Available from: 10.1038/s41443-024-00892-9
Dewsbury DA. Diversity and Adaptation in Rodent Copulatory Behavior: Species differences provide ideal material for a broadened comparative psychology. Science. 1975; 190:947-54. Available from: 10.1126/science.1188377
Romano JE, Keisler DH, Amstalden M. Effect of copulation on estrus duration, LH response, and ovulation in Boer goats. Theriogenology. 2018; 121:62-6. Available from:doi.org/10.1016/j.theriogenology.2018.07.018
Jorge-Neto PN, Luczinski TC, de Araújo GR, Júnior JA, de Souza Traldi A, Dos Santos JA, Requena LA, Gianni MC, de Deco-Souza T, Pizzutto CS, Baldassarre H Can jaguar (Panthera onca) ovulate without copulation?. Theriogenol. 2020; 147:57-61. Available from:doi.org/10.1016/j.theriogenology.2020.02.026
Kumari M, Singh P. Tribulus terrestris improves metronidazole-induced impaired fertility in the male mice. African Health Sciences. 2018; 18:645-52. Available from:10.4314/ahs.v18i3.22
Watcho P, Zelefack F, Nguelefack TB, Ngouela S, Telefo PB, Kamtchouing P, Tsamo E, Kamanyi A. Effects of the aqueous and hexane extracts of Mondia whitei on the sexual behaviour and some fertility parameters of sexually inexperienced male rats. African Journal of Traditional, Complementary and Alternative Medicines. 2007; 4:37-46. Available from:10.4314/ajtcam.v4i1.31190
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