Keywords
male reproductive impairment,
Omega 3 fatty acid,
Selenium,
How to Cite
Abstract
Highly active anti-retroviral therapy (HAART) is currently the main stay in the treatment of Human Immunodeficiency Virus (HIV) disease. This treatment regimen typically combines three or more antiretroviral drugs and like most drug combinations or polypharmacy, has side effects including those on reproductive function which could place HIV patients on HAART under double risk in terms of reproductive function. Part of tissue damage following HAART administration is blamed on oxidative stress. We therefore sought to explore effects of Omega 3 and Selenium, two common antioxidants on HAART-induced male reproductive impairment in a non-HIV animal model. Sixteen male adult Wistar rats weighing 120g to 250g used for the study were grouped into 4 groups of four rats each (control, HAART-only, HAART + Omega 3 and HAART + Selenium groups). Duration of daily administration was six weeks. Results showed no significant changes in pH of epidydimal semen among the groups. Sperm count and viability were significantly reduced in HAART-only compared with control (p<0.05) but increased in HAART + Omega 3 and HAART + Selenium groups compared with HAART-only group (p< 0.05). Sperm motility was significantly reduced in HAART-only compared with control group (p< 0.05). A significantly higher percentage of total sperm defects was observed in HAART-only group compared with control (p <0.05) but significantly lower in the HAART + Selenium compared with HAART-only groups (p<0.05). Serum testosterone was significantly reduced in HAART-only compared with control groups (p<0.05) but significantly increased in HAART + Omega 3 and HAART + Selenium groups compared with HAART- only group (p<0.05). Serum concentration of luteinizing and follicle stimulating hormones were not significantly different among the groups. Testicular concentration of malondialdehyde was significantly increased in HAART-only compared with control (p<0.05) but significantly reduced in HAART + Omega 3 and HAART + Selenium groups compared with HAART-only group (p<0.05 in each). Testicular glutathione peroxidase activity was significantly reduced in HAART-only and HAART + Selenium groups compared with control (p< 0.05), but significantly higher in HAART + Omega 3 and HAART + Selenium compared with HAART-only groups (p<0.05 each). Testicular superoxide dismutase activity was significantly lower in the HAART-only and HAART + Selenium compared with control (p<0.05) but significantly higher in HAART + Omega 3 and HAART + Selenium compared with HAART-only groups (p<0.05 each). Level of tumour necrosis factor – alpha in testes was significantly higher in HAART-only (p<0.05) but lower in the HAART + Selenium (p<0.05) groups compared with control. Tumor necrosis factor–alpha was however significantly reduced in HAART + Omega 3 and HAART + Selenium groups compared with HAART-only (p<0.05 each) groups. Interleukin-6 levels were significantly increased in all HAART-administered groups compared with control (p<0.05 each) though significantly reduced in HAART + Omega 3 and HAART + Selenium compared with HAART-only groups (p<0.05 each). In conclusion, co-administration of Omega 3 or Selenium with HAART ameliorates HAART-induced male reproductive impairment, alteration in redox and inflammatory status in rats.
Keywords: HAART, male reproductive impairment, Omega 3, Selenium
References
Akang, E.N., Dosumu, O.O., Ogbenna, A.A., Akpan, U.U., Ezeukwu, J.C., Odofin, M.O., Oremosu, A.A. and Akanmu, A.S. (2022). The impact of dolutegravir-based combination antiretroviral therapy on the spermatozoa and fertility parameters of men living with HIV. Andrologia 54 (11): e14621 https//pubmed.Acbic.nlm.nih.gov.
Akhigbe, R.E., Hamed, M.A., Odotayo, A.F (2021). HAART and antiKoch’s impair sexual competence, sperm quality and offspring quality when used singly and in combination in male wistar rats. Andrologia. 53: 2 e13951 http//online.library.wiley.com.
Bakare, A.A., Akinseye, K.M., Aminu, B.A and Ofoegbu, F.C (2020). Genetic and Reproductive Toxicity of Lamuvudine, Tenofovir disoproxil fumarati and Efavirenz and their combination in the bone marrow and testicular cells of male mice. Annals of Sci Technol. 5(1):
Bezold, G., Potitch, J.A., Kiviat, N.B., Kuyper, J.M., Wolf, H. and Anderson, D.J (2007). Prevalence of sexually transmitted pathogens in serum from asymptomatic male infertile patients with or without leucocytospermia. Fertil Steril 87: 1087 – 1097.
Brown, K and Arthur, J. (2001). Selenium, Selenoproteins and Human Health: A review. Public Health Nutrition. 4(26): 593 – 599. https://www.cambridges.org.
Brynskov, J., Foegh, P., Pederson, G., Ellervik, C., Kirkegaard, T., Bingham, A., Saermark, T. (2002). Tumour necrosis factor alpha converting enzyme (TACE) activity in colonic mucosa of patients with inflammatory bowel disease. Gut. 51(1): 37 – 43.
Buege, J.A and Aust, S.D (1978). Microsomal Lipid Peroxidation. Methods of Enzymology 52,0241.
Christef, P.N., Charakhanian, S., Thobie, N,, Rozenbaum, W., Nunez, E.A (1992). Evidence for changes in adrenal and testicular steroids during HIV infection. J. Acquir Immune Deficiency Syndrome, 5: 841 – 846.
Constantinescu-Aruxandei, D., Frincu, R.M., Capra, L. and Oancea, F. (2018). Selenium analysis and speciation in Dietary Supplements based on Next-generation selenium ingredients. Nutrients, 10(1466): 1 – 34.
Crittenden, J.A., Handelsman, D.J., Stewart, G.J. (1992). Semen analysis in human immunodeficiency virus infection. Fertile steril 57: 1294 – 1299.
Curdiso, B.R., Hare, A.J., Bush, A.I and Berry, M.J. (2017). Glutathione peroxidase 4: A new player in neurodegeration? Molecular Psychiatry 22: 328 – 335.
Elechi-Amadi, K and Briggs, O. (2018). Superoxide Diamutase and Cortisol levels in HIV-1 patients in Port Harcourt, Nigeria. European Journal of Pharmaceutical and Medical Research. 5(9) 383386
Gough, P and Myles, A (2020). Tumour necrosis receptors: Pleiotropic signaling complexes and their differential effects. Frontiers in Immunology. 11: 585 – 880.
Havlickova, K., Snopkava, S., Pohanka, M., Svacinka, R.J.PH, Ziamal, F., Fabianova, L. and Husa (2021). Antioxidants in patients living with HIV on Antiretrovirals. Military Medical Science Letters – MMSL. 90(2): 54 – 60.
Ho, E., Karimi, G.K., Liu, C.C, Bhindi, R and Figfree, G.A (2013). Biological markers of oxidative stress: Application to Cardiovascular Research and Practice. Redox Biology. 1(1): 483 – 491.
Ivanov, A.V., Valuev-Eliston, V.T., Ivanova, O.N., Kachetkov, S.N., Starondubava, E.S.,, Bartosch B and Isagulians, M.G (2016). Oxidative stress during HIV infection: Mechanisms and Consiquences. Oxidative Medicine and Cellular Longivity. Vol. 2016: 1-8. Article. 8910396.https://doi.org.10.1155/2016/8910.
Kallinge, L.O. (2008). The first postmodern pandemic: 25 years of HIV/AIDS. J. Intern Med. 263(3): 218 – 243.
Khawcharoenpom, T. and Sha, B.E. (2016). HIV infection and infertility. DOI w.5772/62390 www.intechopen.com.
Kimura, A. and Kishinwto, T. (2010). IL-6: Regulation of TReglth17 balance. Euro J. Immunology, 40: 1830 – 1835.
Kushnir, V.A and Lewis, W (2011). Human Immunodeficiency Virus/AIDS and Infertility: emerging problems in the Era of Highly Active Antiretrovirals. Fertil Steril. 96: 546 – 553.
Malata, H.N., Gnanasekaran, N., Melaku, U. and Daniel, S. (2015). Effect of Calpummia aurea seed extract on HAART-induced Hepatotoxicity in Albino wistar rats. Journal of International Blood Research and Reviews. 3(2): 66 – 75.
Marrocco, I., Altieri, F. and Peluso, I. (2017). Measurement and clinical significance of Biomarkers of Oxidative stress in Humans oxidative medicine and cellular longevity. Vol. 2017 Article 11D 6501046: 1 – 32. https://www.hindawi.com/jouranls/omcl/2017
Nair, A.B. and Jacob, S. (2016). A simple practical guide for dose conversion between animals and human. Journal of Basic and Applied Pharmacy. 7(2): 27 – 31. https://www.ncbi/nlm.nih.gov/pmc/articles.
Osonuga, I.O., Osonuga, O.A., Osonuga, A.A. (2010). Gamatotoxic evaluation of oral administration of Zidolam in male Albino rats. Maced. J. Med. Sci. 3(4): 378 – 382.
Oyeyipo, I.P., Skosana, B.T., Everson, F.P., Strijdom, H. and du Plessis, S.S. (2018). Highly Active Antiretroviral Therapy Alters Sperm Parameters and Testicular antioxidant status in loan and Diet-induced obese rats. Toxicological Research. 33(4): 1 – 8.
Rodriguez-Casuriaga, R., Folle, G.A., Santinaque, F., Lopez-Carro, B. and Geisinger, A. (2013). Simple and efficient technique for the preparation of testicular cell suspensions. Journal of Visualized Experiments – JOVE, 78 (50102). https://doi.org/00.379//50102.
Ruffi, F., Brisseau, J.M., Planchon, B., Remi, J.P., Barrier, J.H., Grolleau, J.Y. (1991). Endocrine function in 98 HIV-infected patients: a prospective study. AIDS 5: 729 – 733.
Savasi, V., Parisi, F., Oneta, M., Laoreti, A., Bina, P. and Cetin, I. (2019). PLoSONE 14(2). E021294. https//journals.p/os.org.
Savasi, V., Oneta, M., Laoreti, A., Paris, F, Pamila, B., Duca, P. and Cetin , I (2018). Effects of Antiretroviral Therapy on Sperm DNA Integrity of HIV – 1 – Infected men. Am J. Men’s Health. 12(6): 1835 – 1842.
Sembulingam, K. and Sembulingam, P. (2012). Essentials of Medical Physiology. 6th Edition. Jaypee Brothers, New Delhi, 49 – 62, 467 – 470.
Shevchuk, M.M., Pigato, J.B., Khalife, G., Armenakas, N.A., Fracchia, J.A, (1999). Changing testicular histology in AIDS: its implication for sexual transmission of AIDS. Urology, 53: 203 – 208.
Steyn, F.J., Wan, Y., Clarison, J., Veldhuis, J.D., Herbison, A.E. and Chen, C. (2013). Development of a methodology for and Assessment of Puleafile Luteinizing hormone secretion in Juvenile and Adult Male Mice. Journal of Endocrinology. 154(12): 4939 – 4945.
Tan, X., David, A., Day, J., Tang, H., Dixon, E.R., Zhu H., Chen, Y., Khaing, O., Shikanov, M.K. and Fan, X. (2018). Rapid mouse follicle stimulating hormone quantification and estrus cycle analysis using an automated microfluidic chemiluminescent EliSA System. American Chemical Society. 3(11): 2327 – 2334.
Tanaka, T., Narazaki, M. and Kishimoto, T. (2014). IL-6 in inflammation, immunity and disease. CO12 Sprung Harb. Perspect. Biol 6(10): a016295.
UNAIDS: UNAIDS – 2007. AIDS Epidemic Update (online) 2007. http://data.unaids.org//puts/FPIScides/2007.
Victor, F.C. and Gottlieb A.B. (2002). TNF-alpha and apoptosis: Implications for the pathogenesis and treatment of psoriasis. J. Drugs Dermatol 1(3): 264 – 275.
Weydert, C.J. and Cullen, J.J (2010). Measurement of superoxide dismutase, catalase and glutathione peroxidase in cultured cells and tissue. Nature Protocols. 5(1): 55 – 66.
White, D.J., Mital, D., Taylor, S., St. John, J.C (2001). Sperm Mitchondrial DNA deletion as a consequence of long term HAART Therapy. AIDS 15. 1061 – 1062.
World Health Organization-WHO (2000). WHO laboratory manual for the examination and processing of human semen and semen-cervical mucus interaction. 4th Edition. Cambridge University Press Cambridge. https://www.aab.org/images/WHO%204th%20manual.pdf.
Xie, D., Jiang, L., Lin, Y. and Liu, Z.. (2020). Antioxidant effect of selenium –enriched chrysomyia megacephala (Fabriscius) Larvae powder and its impact on intestinal microflora in D-galactose-induced aging mice. BMC Complementary Medicine and Therapies 20(264). https://doi.org.w.1186/s12906-03058-4.
Yang, L. and Liv, Y. (2017). Structure, function and nutrition of selenium-containing proteins from food stuffs. Mineral – Containing Proteins 1; 89 – 116.
Yoshikawa, T. and Naito, Y. (2002). What is oxidative stress? Journal of the Japan Medical Association. 45(7): 271 – 276. http://www.medi.or.jp/english/pdf/2002.
Zhang, Q., Raoof, M., Chen, Y., Sunii, Y., Sursal, T., Junger, W., Brohi, K., Hagaki, K., Hauser, C. J. (2010). Circulating mitochondrial DAMFs cause inflammatory response to injury. Nature. 464: 104 – 107.
Zhou, J., Chen, L., Li, J., Li, H., Hong, Z., Xie, M, Chen, S and Yao, B. (2015). The semen pH affects sperm motility and capacitation.
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