Exposure to Fluoxetine induced Gonado-toxicity in female rats: Modulating role of Hybanthus enneaspermus

Muhammed A. Dikwa(1), Monsurat B. Falana(2), Muhammed R. Asinmi(3), Musbau A. Akanji(4), Quadri O. Nurudeen(5),


(1) Federal University, Dutse, Nigeria
(2) Al-Hikmah University, Ilorin, Nigeria
(3) Al-Hikmah University, Ilorin, Nigeria.
(4) Kwara State University, Malete, Nigeria
(5) Al-Hikmah University, Ilorin, Nigeria
Corresponding Author

Abstract


Several scientific evidence supports the use of Hybanthus enneaspermus leaves in the management of female sexual inadequacies. Additionally, fluoxetine is a reproductive toxicant that induces sexual dysfunction. To determine the modulating role of aqueous extract of Hybanthus enneaspermus leaves on fluoxetine-induced gonado-toxicity, sixty healthy, sexually-responsive female rats (157.21 ± 6.89) were divided into six groups (A–F) comprising of 10 rats each. Group A (control group) were administered distilled water only, Group B-F received orally 15 mg/kg body weight (b.w) of fluoxetine prepared daily for 14 days for the induction of anti-oestrogenicity and subsequently received 0.5ml of distilled water, 20 mg/kg b.w of a reference drug (Tadalafil) and 0.5 mL equivalent to 250, 500 and 1000 mg/kg b.w of the extract respectively, orally, once daily (08:00-08:45h) for 7 days. Fluoxetine reduced serum oestrogen concentrations by 54.79% and significantly reduced (p<0.05) ovarian and uterine total protein, glycogen, cholesterol, the activities of alkaline phosphatase and acid phosphatase. The reductions were by (22.91%, 25.57%, 22.82 %, 15.09 % and 43.17 %) in the ovaries and (21.25 %, 26.9%, 7.20%, 16.82% and 29.85%) in the uteri of the animals respectively. In contrast, these reductions were overturned by the extract towards the control group. The extract at 1000 mg/kg b.w ameliorated the reductions of these oestrogenic indices. Hybanthus enneaspermus attenuated the deleterious effects of fluoxetine on the ovaries and uteri, restored sexual competence and promoted oogenesis. These may further lend backing to its widespread use in handling some sterility/infertility problems in women.

 


Keywords


Hybanthus enneaspermus, fluoxetine, gonado-toxicity

References


Chen J (2016). The pathophysiology of delayed ejaculation. Translational Andrology and Urology, 5(4), 549-562.

Dalton L (2022). Understanding the Female Reproductive Tract’s Role in Fertilization. ACS Central Science, 8(1), 3–6

Dikwa MA, Asinmi MR, Falana MB, Nurudeen QO, & Akanji MA (2023). Aqueous extract of Hybanthus enneaspermus exhibited aphrodisiac potentials in fluoxetine-induced sexually impaired female rats. Mediterranean Journal of Pharmacy and Pharmaceutical Sciences. 3(4), 61-72.

Domingues RR, Wiltbank MC, & Hernandez LL (2023). The antidepressant fluoxetine (Prozac®) modulates estrogen signaling in the uterus and alters estrous cycles in mice. Molecular and Cellular Endocrinology, 559, 1-16.

Du Q, Chan LY, Gilding EK, Henriques ST, Condon ND, Ravipati AS, & Craik DJ (2020). Discovery and mechanistic studies of cytotoxic cyclotides from the medicinal herb Hybanthus enneaspermus. Journal of Biological Chemistry, 295(32), 10911-10925.

Friedewald WT, Levy RI, & Fredrickson DS (1972). Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clinical Chemistry, 18(6), 499 –502.

Gök S, Gök BC, Alataş E, Senol H, & Topak OZ (2023). Effects of Selective Serotonin Reuptake Inhibitor Treatment on Ovarian Reserves in Patients with Depression. Medicina, 59(3), 517.

Gornall AG, Bardawill CJ, & David MM (1949). Determination of serum proteins by means of the biuret reaction. Journal of Biological Chemistry, 177(2), 751-766.

Javid FA & Afshinjavid S (2015). The effect of fluoxetine on human ovarian carcinoma cells. Clinical Therapeutics, 37(8), 35-36.

Kemp A & Van Heijningen AJ (1954). A colorimetric micromethod for the determination of glycogen in tissues. Biochemical Journal, 56(4), 646-648.

Lei W, Nguyen H, Brown N, Ni H, Kiffer-Moreira T, Reese J, & Paria BC (2013). Alkaline phosphatases contribute to uterine receptivity, implantation, decidualization and defense against bacterial endotoxin in hamsters. Reproduction, 146(5), 419-433.

Mazaro-Costa R, Andersen ML, Hachul H, & Tufik S (2010). Medicinal plants as alternative treatments for female sexual dysfunction: utopian vision or possible treatment in climacteric women? Journal of Sexual Medicine, 7(11), 3695-3714.

Metcalfe KA, Lynch HT, Ghadirian P, Tung N, Olivotto IA, Foulkes WD, Warner E, Olopade O, Eisen A, Weber B, McLennan J, Sun P, & Narod SA (2005) The risk of ovarian cancer after breast cancer in BRCA1 and BRCA2 carriers. Gynecologic Oncology, 96(1), 222-226.

Miller WL & Bose HS (2011). Early steps in steroidogenesis: intracellular cholesterol trafficking: thematic review series: genetics of human lipid diseases. Journal of Lipid Research, 52(12), 2111-2135.

Nurudeen QO & Yakubu MT (2016). Aqueous extract of Phyllanthus amarus leaves restores sexual competence in female rats induced into sexual dysfunction by fluoxetine. Nigerian Journal of Biochemistry and Molecular Biology, 31(1), 1-14.

Nurudeen QO, Asinmi MR, Falana MB, & Dikwa MA (2023). Aphrodisiac Potentials of Aqueous Extract of Azanza garckeana Fruit Pulp in Fluoxetine-induced Sexually impaired Female Rats. Journal of Science and Technology, 15(2), 11-22.

Patel DK, Kumar R, Sairam K, & Hemalatha S (2013). Hybanthus enneaspermus (L.) F. Muell: a concise report on its phytopharmacological aspects. Chinese Journal of Natural Medicines, 11(3): 199-206.

Petrucelli N, Daly MB, & Pal T (2022). BRCA1-and BRCA2-associated hereditary breast and ovarian cancer, National Library of Medicine, 1-32.

Rajsekhar PB, Bharani RA, Angel KJ, Ramachandran M, & Rajsekhar SPV (2016). Hybanthus enneaspermus (L) F. Muell: A phytopharmacological review on herbal medicine. Journal of Chemical and Pharmaceutical Research, 8(1), 351-355.

Richards JS & Pangas SA (2010). The ovary: basic biology and clinical implications. The Journal of Clinical Investigation, 120(4), 963-972.

Rodrigues P, Limback D, McGinnis L, Marques M, Aibar J, & Plancha, CE (2021). Germ–somatic cell interactions are involved in establishing the follicle reserve in mammals. Frontiers in Cell and Developmental Biology, 9, 1-7.

Romero-Reyes J, Cárdenas M, Damián-Matsumura P, Domínguez R, & Ayala ME (2016). Inhibition of serotonin reuptake in the prepubertal rat ovary by fluoxetine and effects on ovarian functions. Reproductive Toxicology, 59, 80-88.

Rudmann DG & Foley GL (2013). Female reproductive system. Haschek and Rousseaux's Handbook of Toxicologic Pathology, 2599-2663.

Tahir MS, Nguyen LT, Schulz BL, Boe-Hansen GA, Thomas MG, Moore SS, & Fortes MR (2019). Proteomics recapitulates ovarian proteins relevant to puberty and fertility in Brahman Heifers (Bos indicus L.). Genes, 10(11), 923-950.

Tietz NW (1995). Clinical Guide to Laboratory Tests. 3rd edition. Philadelphia: W.B. Saunders Company. pp. 1096

Wang IY, Cornillie FJ, Barsamian S, Street D, Manconi F, & Fraser IS (1999). Endometrial lysosomal enzyme activity in normal cycling endometrium. Molecular Human Reproduction, 5(1), 79-83.

Wang IY, Fraser IS, Barsamian SP, Manconi F, Street DJ, Cornillie FJ, & Russell P (2000). Endometrial lysosomal enzyme activity in ovulatory dysfunctional uterine bleeding, IUCD users, and post-partum women. Molecular Human Reproduction, 6(3), 258-263.

Wright PJ, Leathwood PD, & Plummer DT (1972a). Enzymes in rat urine: Acid phosphatase. Enzymologia, 42(6), 459-462.

Wright PJ, Leathwood PD, & Plummer DT (1972b). Enzymes in rat urine: Alkaline phosphatase. Enzymologia, 42(4), 317- 327.

Yao HH (2005). The pathway to femaleness: current knowledge on embryonic development of the ovary. Molecular and Cellular Endocrinology, 230(1-2), 87-93.


Full Text: PDF

Article Metrics

Abstract View : 56 times
PDF Download : 9 times

DOI: 10.57046/KMEF8268

Refbacks

  • There are currently no refbacks.


Copyright (c) 2024 Proceedings of the Nigerian Academy of Science

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.