Therapeutic potential of virgin coconut oil in mitigating sodium benzoate- model of male infertility: Role of Nrf2/Hmox-1/NF-kB signaling pathway

Document Type : Original Article


1 Department of Physiology, Faculty of Basic Medical Sciences, College of Medicine and Health Sciences, Lead City University Ibadan, Oyo State, Nigeria

2 Department of Physiology, Ekiti-State University, Ado-Ekiti, Ekiti-State, Nigeria

3 Department of Physiology, Ekiti- State University, Ado-Ekiti, Ekiti-State, Nigeria

4 Department of Pharmacology& Toxicology, College of Pharmacy, Afe Babalola University, Ado-Ekiti, Ekiti-State, Nigeria

5 Department of Physiology, Faculty of Basic Medical Sciences, College of Health Sciences, University of Ilorin. Nigeria

6 Federal University of Health Sciences, Ila Orangun, Osun State, Nigeria


Objective(s): Male infertility is a major public health issue due to increased prevalence, so there is an urgent need for a therapeutic solution. The search for a natural dietary substance that could modulate redox balance and inflammation and protect testicular function is in demand. Virgin Coconut Oil (VCO) has found use in the treatment of diabetes, and cancer owing to the presence of polyphenols. However, there is a dearth of information on its effect on testicular toxicity. The present study investigated VCO as a possible treatment for testicular toxicity in the Sodium Benzoate (SB) model of male infertility by evaluating the oxidative and inflammatory status, circulating hormonal levels, and key sperm indices.
Materials and Methods: Twenty adult male rats were randomly assigned to four groups of 5 rats each and were treated with normal saline, sodium benzoate, sodium benzoate+5% VCO, and sodium benzoate+15% VCO for 30 days respectively. Biochemical analysis of reproductive hormones was assessed. Sperm parameters assessed include sperm function tests and sperm kinematics. One-way analysis of variance (ANOVA) followed by post hoc Tukey tests was performed.
Results: 5% VCO reverts the deranged serum reproductive hormones caused by sodium benzoate. 5% VCO was more potent as an antioxidant and anti-inflammatory treatment than 15% VCO. However, both doses prevented SB’s effect on the sperm function test and kinematics.
Conclusion: VCO-supplemented diet can ameliorate SB-induced testicular toxicity by inhibiting its mechanisms of toxicity that are related to oxidative stress, apoptosis, and inflammation.


Main Subjects

1. Cram D, Moirak O, David MD. Male infertility genetics-The future. J Androl 2001;22:738-746. 
2. Stukenborg JB, Mitchell RT, Söder O. Endocrine disruptors and the male reproductive system. Best Pract Res Clin Endocrinol Metab 2021;35:101567. 
3. Sharma P, Kaur P, Ghanghas P, Kaur J, Kaushal N. Selenium ameliorates ibuprofen induced testicular toxicity by redox regulation. Reprod Toxicol 2020;96:349-358. 
4. Caroppo E, Campagna C, Colpi EM, D’Amato G, Colpi GM. Sperm source does not affect the ICSI outcome of patients with severely compromised spermatogenesis. Andrologia 2020; 52: e13884. 
5. Minhas S, Bettocchi C, Boeri L, Capogrosso P, Carvalho J, Cilesiz NC, et al. European association of urology guidelines on male sexual and reproductive health: 2021 update on male infertility. Eur Urol 2021;80:603-620. 
6. Kehinde OS, Christianah OI, Oyetunji OA. Ascorbic acid and sodium benzoate synergistically aggravates testicular dysfunction in adult Wistar rats. Int J Physiol Pathophysiol Pharmacol 2018;10:39-46. 
7. El-Shennawy L, Kamel MAE naby, Khalaf AHY, Yousef MI. Dose-dependent reproductive toxicity of sodium benzoate in male rats: Inflammation, oxidative stress and apoptosis. Reprod Toxicol 2020;98:92-98. 
8. Micol LA, Cakir ÖO, Sangster P, Ralph DJ. Stimulation of leydig and sertoli cellular secretory function by anti-oestrogens: Clomiphene. Curr Pharm Des 2021;27:2669-2681. 
9. Huijben M, Huijsmans RLN, Lock MTWT, de Kemp VF, de Kort LMO, van Breda JHMK. Clomiphene citrate for male infertility: A systematic review and meta‐analysis. Andrology 2023;11:987-996. 
10. Law KS, Azman N, Omar EA, Musa MY, Yusoff NM, Sulaiman SA, et al. The effects of virgin coconut oil (VCO) as supplementation on quality of life (QOL) among breast cancer patients. Lipids Health Dis 2014;13:139-145. 
11. Prakhin EI, MVMVIFVGB, LNAlekseenko. The efficacy of using laser therapy in acute segmental bronchopneumonia in young children. Vopr Kurortol Fizioter Lech Fiz Kult 1989;6:44-45. 
12. Lokesh SB, Kini RD, Arunkumar N, Shetty B S, N A, K B. Effects of virgin coconut oil on testicular toxicity induced by Cadmium in rats. Res J Pharm Technol 2021;14:4630-4634. 
13. Couto M, Cates C. Laboratory guidelines for animal care. Vertebrate Embryogenesis: Embryological, Cellular, and Genetic Methods. 2019:407-30. 
14. Khan IS, Dar KB, Ganie SA, Ali MdN. Toxicological impact of sodium benzoate on inflammatory cytokines, oxidative stress and biochemical markers in male Wistar rats. Drug Chem Toxicol 2022;45:1345-1354. 
15. Azubuike-Osu SO, Famurewa AC, David JC, Abi I, Ogbu PN, Oparaji CK, et al. Virgin coconut oil resists arsenic-induced cerebral neurotoxicity and cholesterol imbalance via suppression of oxidative stress, adenosine deaminase and acetylcholinesterase activities in rats. Nat Prod Commun 2021;16:1934578X2110169. 
16. Famurewa AC, Folawiyo AM, Enohnyaket EB, Azubuike-Osu SO, Abi I, et al. Beneficial role of virgin coconut oil supplementation against acute methotrexate chemotherapy-induced oxidative toxicity and inflammation in rats. Integr Med Res 2018;7:257-263. 
17. Akintoye OO, Ajibare AJ, Omotuyi IO. Virgin coconut oil reverses behavioral phenotypes of letrozole-model of PCOS in Wistar rats via modulation of NRF2 upregulation. J Taibah Univ Med Sci 2023;18:831-841.
18. Akhigbe R, Ajayi A. Testicular toxicity following chronic codeine administration is via oxidative DNA damage and up-regulation of NO/TNF-α and caspase 3 activities. PLoS One 2020;15:e0224052. 
19. Basaria S. Male hypogonadism. Lancet 2014;383:1250-1263. 
20. Phillipps HR, Yip SH, Grattan DR. Patterns of prolactin secretion. Mol Cell Endocrinol 2020;502:110679. 
21. Schulster M, Bernie A, Ramasamy R. The role of estradiol in male reproductive function. Asian J Androl 2016;18:435-440. 
22. Nandi A, Yan LJ, Jana CK, Das N. Role of catalase in oxidative stress- and age-associated degenerative diseases. Oxid Med Cell Longev 2019;2019:1-19. 
23. Couto N, Wood J, Barber J. The role of glutathione reductase and related enzymes on cellular redox homoeostasis network. Free Radic Biol Med 2016;95:27-42. 
24. Ma Q. Role of Nrf2 in oxidative stress and toxicity. Annu Rev Pharmacol Toxicol 2013;53:401-426. 
25. Consoli V, Sorrenti V, Grosso S, Vanella L. Heme oxygenase-1 signaling and redox homeostasis in physiopathological conditions. Biomolecules 2021;11:589-611. 
26. Redza-Dutordoir M, Averill-Bates DA. Activation of apoptosis signalling pathways by reactive oxygen species. Biochim Biophys Acta 2016;1863:2977-2992. 
27. Liu T, Zhang L, Joo D, Sun SC. NF-κB signaling in inflammation. Signal Transduct Target Ther 2017 ;2:17023. 
28. Yoon WK, Kim YW, Suh SIL, Choi R, Lee SG, Hyun C. Evaluation of cardiopulmonary and inflammatory markers in dogs with heartworm infection during treatment with the 2014 American Heartworm Society recommended treatment protocol. Parasit Vectors. 2017;10:535-542. 
29. George JW, Dille EA, Heckert LL. Current concepts of follicle-stimulating hormone receptor gene regulation1. Biol Reprod 2011;84:7-17. 
30. Heindel JJ, Vandenberg LN. Developmental origins of health and disease. Curr Opin Pediatr 2015;27:248-253. 
31. Yung Y, Aviel-Ronen S, Maman E, Rubinstein N, Avivi C, Orvieto R, et al. Localization of luteinizing hormone receptor protein in the human ovary. Mol Hum Reprod 2014;20:844-849. 
32. Couse JF, Mahato D, Eddy EM, Korach KS. Molecular mechanism of estrogen action in the male: insights from the estrogen receptor null mice. Reprod Fertil Dev 2001;13:211-219. 
33. Talwar P, Hayatnagarkar S. Sperm function test. J Hum Reprod Sci 2015;8:61. 
34. Mortimer ST, Swan MA. Variable kinematics of capacitating human spermatozoa. Hum Reprod 1995;10:3178-3182. 
35. Mortimer ST, Maxwell WMC. Kinematic definition of ram sperm hyperactivation. Reprod Fertil Dev 1999;11:25-30. 
36. Famurewa AC, Ufebe OG, Egedigwe CA, Nwankwo OE, Obaje GS. Virgin coconut oil supplementation attenuates acute chemotherapy hepatotoxicity induced by anticancer drug methotrexate via inhibition of oxidative stress in rats. Biomed  Pharmacother 2017;87:437-442. 
37. Varma SR, Sivaprakasam TO, Arumugam I, Dilip N, Raghuraman M, Pavan KB, et al. In vitro anti-inflammatory and skin protective properties of virgin coconut oil. J Tradit Complement Med 2019;9:5-14. 
38. Dalal Redouane YBMGAHNMDS and OKheroua. Sodium benzoate effects on Swiss mice reproductive function. Biosci Res 2019;16:287-298. 
39. Oduwole OO, Peltoketo H, Huhtaniemi IT. Role of follicle-stimulating hormone in spermatogenesis. Front Endocrinol (Lausanne) 2018;9:763-773. 
40. Walker WH and CJ. FSH and testosterone signaling in Sertoli cells. Reproduction 2005;130:15-28. 
41. Dhindsa S. Pathy’s Principles and Practice of Geriatric Medicine. Sinclair AJ, Morley JE, Vellas B, editors. Vol. 15. Wiley; 2012. 1073-1085 p. 
42. Panza S, Giordano F, De Rose D, Panno ML, De Amicis F, Santoro M, et al. FSH-R human early male genital tract, testicular tumors and sperm: Its involvement in testicular disorders. Life 2020;10:336-354. 
43. Azuma SL, Quartey NKA, Ofosu IW. Sodium benzoate in non-alcoholic carbonated (soft) drinks: Exposure and health risks. Sci Afr. 2020;10:e00611. 
44. Verma P, Naik S, Nanda P, Banerjee S, Naik S, Ghosh A. In vitro anticancer activity of virgin coconut oil and its fractions in liver and oral cancer cells. Anticancer Agents Med Chem 2020;19:2223-2230. 
45. Adamczewska D, Słowikowska-Hilczer J, Walczak-Jędrzejowska R. The fate of leydig cells in men with spermatogenic failure. Life 2022;12:570-598. 
46. Chatterjee S. Oxidative Stress, Inflammation, and Disease. In: Oxidative Stress and Biomaterials. Elsevier; 2016. p. 35-58. 
47. Marina AM, Che Man YB, Amin I. Virgin coconut oil: Emerging functional food oil. Trends Food Sci Technol 2009;20:481-487. 
48. Nakamura BN, Lawson G, Chan JY, Banuelos J, Cortés MM, Hoang YD, et al. Knockout of the transcription factor NRF2 disrupts spermatogenesis in an age-dependent manner. Free Radic Biol Med 2010;49:1368-1379. 
49. Otterbein LE, Choi AMK. Heme oxygenase: Colors of defense against cellular stress. Am J Physiol Lung Cell Mol Physiol 2000;279:L1029-1037. 
50. Wajda A, Łapczuk J, Grabowska M, Słojewski M, Laszczyńska M, Urasińska E, et al. Nuclear factor E2-related factor-2 (Nrf2) expression and regulation in male reproductive tract. Pharmacol Rep 2016;68:101-108. 
51. Malik I, Durairajanayagam D, Singh H. Leptin and its actions on reproduction in males. Asian J Androl 2019;21:296-299. 
52. Brown JM, Wilson G. Apoptosis genes and resistance to cancer therapy: What does the experimental and clinical data tell us? Cancer Biol Ther 2003;2:477-490. 
53. Ekeleme-Egedigwe CA, Famurewa AC, David EE, Eleazu CO, Egedigwe UO. Antioxidant potential of garlic oil supplementation prevents cyclophosphamide-induced oxidative testicular damage and endocrine depletion in rats. J Nutr Intermed Metab 2019;18:100109. 
54. Leiro J, Álvarez E, Arranz JA, Laguna R, Uriarte E, Orallo F. Effects of cis -resveratrol on inflammatory murine macrophages: antioxidant activity and down-regulation of inflammatory genes. J Leukoc Biol 2004;75:1156-1165. 
55. Farag OM, Abd-Elsalam RM, El Badawy SA, Ogaly HA, Alsherbiny MA, Ahmed KA. Portulaca oleracea seeds’ extract alleviates acrylamide-induced testicular dysfunction by promoting oxidative status and steroidogenic pathway in rats. BMC Complement Med Ther 2021;21:122-136.