The Influence of Prolonged Administration of Honey on Testicular and Prostate Architectures in Adult Wistar Rats

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American-Eurasian Journal of Toxicological Sciences 5 (1): 36-40, 2013 ISSN 2079-2050 IDOSI Publications, 2013 DOI: 10.5829/idosi.aejts.2013.5.1.73173 The Influence of Prolonged Administration of Honey on Testicular and Prostate Architectures in Adult Wistar Rats 1 2 3 W.N. Dare, P.S. Igbigbi and A.C. Odike 1 Department of Human Anatomy, College of Health Sciences, Niger Delta University, Wilberforce Island, Nigeria 2 Department of Human Anatomy, College of Health Sciences, Delta State University, Abraka, Nigeria 3 Department of Pathology, College of Medicine, Ambrose Alli University, Ekpoma, Nigeria Abstract: This investigation was designed to determine the effect of prolonged administration of honey on testicular and prostate architectures in adult male Wistar rats. A total of twenty five male rats weighing between 210 220g were used for the study. They were divided into three groups of two experimental and one control of ten rats and five rats respectively. Groups 1 and 2 were administered with 5ml/kg body weight and 7.5ml/kg body weight of honey once daily twice a week for ten weeks and rest for ten weeks. The testicular and prostate architectures of five rats from each experimental group were examined histologically at the end of administration and the remaining five after ten weeks of treatment rest and results compared with control. Results at the end of treatment and rest revealed that prolonged consumption of honey has harmful effects on the testis and prostate of Wistar rats. Histological changes were observed in the testes at the end of administration and rest. There was mild/moderate and severe dose dependent hyperplastic changes in prostate architecture at the end of treatment but no further change after rest. Prolonged intake of honey has a deleterious effect on the testes and prostate in rats. Key words: Honey Excessive Prolong Testes Prostate Wister Rats INTRODUCTION wounds have been reported to be safe [16, 17] as it reduces inflammation in deep [16] and superficial [18] From primevaltimes, natural products such as burns as well as in wounds [19]. A 1% v/v of honey is honey and flora have served as food and medicine for known to stimulate growth of monocytes in cell cultures man [1-4]. Currently, information on the use of honey for to release cytokineswhich activate the immune response the treatment of many human diseases abound in to infection [20]. Abuharfeil et al. [21] also reported that magazines, bee keeping journals [5] and natural products honey concentration as low as 0.1% stimulated the leaflets, suggesting a wide variety of unfounded proliferation of peripheral blood B-lymphocytes and properties. On the contrary, reports supported by T-lymphocytes in cell. The bacterial destroying activity of scientific tests are few and far between [1, 6-8]. Honey is macrophages may have been assisted by the also considered a part of traditional medicine [9]. It is carbohydrate content of honey principally, glucose and effective in the healing of wounds and burns and the fructose [22] and by its ph of 3 to 4 [23]. Honey is said to treatment of diabetic ulcers, [10-14], cough suppression have an inhibitory effect to several species of bacteria [15]. Honey is produced from many floral sources and its including aerobes and anaerobes, Gram-positives and content and activity vary with its origin and processing Gram-negatives [24] and an antifungal action on some technique [1]. Histological studies of honey applied to yeasts and species of Aspergillus and Penicillium [25], as Corresponding Author: W.N. Dare, Department of Human Anatomy, College of Health Sciences, Niger Delta University, Wilberforce Island, Nigeria. 36

well as some dermatophytes [26]. Wounds infected with Post-Treatment Study (Treatment Rest): The remaining Pseudomonas, showing resistance to several antibiotics, unsacrificed experimental rats, five from each group have been rapidly cleared of infection with honey and were maintained with normal feed (no treatment) allowing successful skin grafting [27]. Application of for another 10 weeks, then sacrificed and were processed honey to open wounds has been reported to be soothing for testicular and prostate architectures for possible [28] to relieve pain [28] and with no adverse effects [29]. reversal of influence and were compared with control The aim of this study was to establish whether excessive animals. consumption of bee honey in varying doses have effect on testicular and prostate gland histology. Statistical Analysis: All parameters studied both experimental and control groups were compared, using the MATERIALS AND METHODS two-way analysis of variance (ANOVA) to test the observations. Twenty five adult male Wistar rats were used for this study. The rats were collected from the Animal House of RESULTS the College of Medicine, Ambrose Alli University, Ekpoma, Edo State Nigeria. They weighed between Testicular Histology: There were obvious significant 210-220g and were acclimatised for two weeks, had access histological changes observed in the testes in both to water ad libitum. Feeds (growers) were obtained from experimental groups at end of administration and rest Bendel Flour Mills Plc, Ewu, Edo State and honey was as compared with control. Honey altered the purchased locally from M.C Super Market Ekpoma. testicular architecture of rats at the light microscopic The animals were caged separately for the purpose of level. The cells appearedabnormal in both identification. The experimental protocol for animal experimental groups as shown in the photomicrographs. research was approved by the ethics committee of the There were microscopic pathological changes in the cells College of Health Sciences, Delta State University, of the testes of the two experimental groups as compared Abraka. with control. Experimental Design: Twenty rats were used as experimental and five as control. They were divided into two experimental groups of ten rats each and one control group of five rats. The experimental rats were administered with two varying doses of bee honey. Group 1: Rats were administered with 5ml/kg body weight of bee honey through orogastric tube (gavage) once a day twice weekly for ten weeks. Group 2: Rats were administered with higher dose of 7.5ml/kg body weight, once a day twice a week for the same duration. Group 3: Served as control with normal feed only. Testicular and Prostate Architecture: At the end of 10 weeks treatment, five rats from each experimental group and control were sacrificed by guillotine decapitation. Testis and prostates of sacrificed experimental and control animals were exposed and removed by orchidectomy and prostatectomy; processed and stained with H&E for testicular and prostate architectural changes and results compared. Prostate Architecture: Prolonged administration of honey significantly affected the architecture of the prostate. The prostate revealed mild/moderate nodular hyperplasia in group 1 animals treated with 5ml/kg body weight and severe hyperplasia in group 2 animals treated with 7.5ml/kg body weight as revealed in the photomicrographs. The cells of the gland were more numerous and fibro muscular tissue more prominent. The effect was dose dependent. Post-Treatment Effect (Treatment Rest) Testicular Architecture: The pathological changes were more severe in the testes after 10 weeks of treatment rest as compared with control animals. Damage to testicular architecture was worse in both experimental groups than end of administration. Prostate Histology: No further change was observed in the architecture of prostate. The prostate architecture appeared similar to end of treatment. The results showed that the negative effect of honey on the prostate gland did not progress further during the ten weeks period of treatment rest. However, the effect was irreversible after cessation of treatment for ten weeks. 37

Fig. 1: Experimental group 1 photomicrograph ( 100) Fig. 4: Experimental group 1 photomicrograph ( 400) showing abnormaltesticulararchitecture with showing mild/moderate nodular prostatic obvious degenerative changes in the hyperplasia. Arrows pointing at increased cell histologicalsections. The semineferoustubules population (hyperplasia) aroundthe lumen of the look bizarre in appearance with necrotic cells. gland. Fig. 2: Experimental group 2 photomicrograph ( 100) Fig. 5: Group 2 photomicrograph ( 400) showing severe showing abnormal testicular architecture,with nodular prostatic hyperplasia. The hyperplastic increase inter-tubular gaps as a result of cells are seen (short arrows) around the luminal semineferous tubule shrinkage (arrows). surfaces of the tubules. Also shown is the supporting stroma (long arrows) which is a mixture of collagenous fibrous tissue and smooth muscle fibres with flat cells. Accumulation of secretions AS is seen in the glandular lumen. Fig. 3: Group 3, (control) photomicrograph ( 100) showing normal testiculararchitecture. Semineferous tubules and inter-tubular boundaries are clearly shown. DISCUSSION Fig. 6: Group 3 photomicrograph ( 400) of control Despite the many purported health benefits of honey showing normal prostate architecture. The arrows as antibacterial agent [5] wound dressing, cough showed normal prostatic cells at the luminal suppression [15], gastroenteritis, diabetes [7], gastric surfaces of the gland. 38

ulcers, wound healing [10-12] not many works have 2. Al-Naggar, R.A., Y.V. Bobryshev, M. Abdulghani, been done on the effect of honey on the testes S. Rammohan, M.T. Osman and S.Y. Abdul Kadir, and prostate of animals and man. This study 2013. Complementary/alternative Medicine Use focused on the effect of prolonged administration of among Cancer Patients in Malaysia. World Journal of honey on testicular and prostate architectures in male Medical Sciences, 8(2): 157-164. Wistar rats. 3. Maobe, A.G., L. Gitu, E. Gatebe, H. Rotich, The study showed that prolonged administration of P.N. Karanja, D.M. Votha, I.W. Nderitu and honey, an exogenous substance is toxic to the testes and W. Kungu, 2013. Antifungal Activity of Eight prostate gland. It altered the structural architecture of Selected Medicinal Herbs Used for thetreatment of these two organs. There were obvious light Diabetes, Malaria and Pneumonia in Kisii Region, microscopic changes in the histological sections of the Southwest Kenya. World Journal of Medical testis. The germ cells of the testes of the experimental and Sciences, 8(1): 74-78. control animals looked different under the light 4. Borhan, M., A. Rezaei, D. Mohajeri and microscope. The seminiferous tubules and the cells of the S. Safarmashaei, 2012. Comparison of In vivo Wound testis appeared degenerated. In fact, there was clear cut Healing Activity of Verbascum Thapsus Flower difference observed between the experimental and control Extract with Zinc Oxide on Experimental Wound animals as shown in the photomicrographs. From these Model in Rabbits. American-Eurasian Journal of observations, one may safely deduce that excessive and Toxicological Sciences, 4(1): 24-30. prolongedintake of honey has harmful effect on testicular 5. White, R., P. Molan and R. Copper, eds 2005. Honey: architecture. A Modern Wound Management Product. Wounds The prostatic architecture was distorted, the cells of UK, Aberdeen, UK. the experimental groups of the prostate appeared larger 6. Postmes, T., A.E. Van den Bogaard and M. Hazen, (hypertrophic) and more in numerous (hyperplastic) than 1993. Honey for wounds, ulcers and skin graft the control group. These architectural changes were more preservation. Lancet, 341: 756-757. prominent in group 2 animals (severe hyperplasia) which 7. Mann, J.I., 1987. Simple sugars and diabetics, received higher dose (7.5ml/kg body weight) than group Diabetic Med., 4: 135. 1 with lesser dose 5ml/kg body weight (mild/moderate 8. Efem, S.E., 1988. Clinical observations on the wound hyperplasia).the effect was dose dependent. Prolonged healing properties of honey. Br J. Surg., 75: 679-81. honey intake has negative influence on prostate 9. Abdul-Ghani, A.S., N. Dabdoub, R. Muhammad, architecture (enlargement of prostate). R. Abdul-Ghani and M. Qazzaz, 2008. Effect of The histological appearances of the gland in the two Palestinian Honey on Spermatogenesis in Rats. J. experimental animals at the end of treatment and after Med. Food, 11(4): 799-802. treatment rest were similar. There were no further changes 10. Green, A.E., 1988. Wound healing properties of after 10 weeks of treatment rest, that is, the prostatic honey. Br J. Surg., 75: 1278-1283. tissue appeared similar at the end of treatment and after 11. Cooper, R., 2001. How does honey heal wounds? In: rest. Honey and Healing (Munn P, Jones R, Eds.). IBRA International Bee Research Association. Cardiff, UK, CONCLUSION pp: 27-34. 12. Davies, P., 2005. Recent clinical usage of honey in the This study has demonstrated that prolonged treatment of wounds. Wounds UK (Honey Supp), ingestion of honey has harmful effect on the testesand pp: 14-22. prostate. It causes irreversible damage to both testicular 13. White, R., P. Molan and R. Copper, eds 2005. Honey: and prostate architectures. However, further investigation A Modern Wound Management Product. Wounds should be conducted to support or contradict these UK, Aberdeen, UK. claims. 14. Eddy, J.J. and M.D. Gideon, 2005. Topical honey for diabetic foot ulcers, J. FamPract., 54: 533-535. REFERENCES 15. World Health Organization, 2001. Cough and Cold Remedies for the Treatment of Acute Respiratory 1. Echazarreta, C.M and A.E. Jeffrey, 1996. Medical uses Infections in Young Children. Department of Child of honey. Rev. Biomed, 7: 43-49. and Adolescent Health Geneva, Swizerland. 39

16. Postmes, T.J., M.C. Bosch, R. Dutrieux, J. van Baare 22. Crane, E.A., 1980. Book of Honey, published in New and M.J. Hoekstra, 1997. Speeding up the healing of York Charles Scribner s Sons. burns with honey. An experimental study with 23. Ryan, G.B. and G. Majno, 1977. Inflammation. histological assessment of wound biopsies. In: Kalamazoo, Michigan: Upjohn, pp: 80. Mizrahi A, Lensky Y, eds. Bee Products: Properties, 24. Molan, P.C., 1992. The antibacterial activity of honey. Applications and Apitherapy. New York: Plenum 1. The nature of the antibacterial activity. Bee World Press, pp: 27-37. 73: 5-28. 17. Abdel El-Banby, M., A. Kandil, G. Abou-Sehly, 25. Molan, P.C., 1992. The antibacterial activity of honey. M.E. El-Sherifand K. Wahed K, 1989. Healing effect 2. Variations in the potency of the antibacterial of floral honey and honey from sugar-fed bees on activity. Bee World, 73: 59-76. surgical wounds (animal model), Fourth International 26. Brady, N.F. and P.C. Molan P C, 1977. Pharm Sci., Conference on Apiculture in Tropical Climates, Cairo. 2: 1-3. International Bee Research Association, London. 27. Dunford, C., R. Cooper and P. Molan, 2000. Using 18. Burlando, F., 1978. honey as a dressing for infected skin lesions. Nurs Sull'azioneterapeuticadelmielenelleustioni. Minerva Times, 96: 7-9. Dermatol, 113: 699-706. 28. Subrahmanyam, M., 1993. Honey impregnated gauze 19. Oryan, A. and S.R. Zaker, 1998. Effects of topical versus polyurethane film (OpSite ) in the treatment application of honey on cutaneous wound healing in of burns - a prospective randomized study. Br J. Plast rabbits. J. Vet. Med. Series A, 45(3): 187-8. Surg., 46(4): 322-323. 20. Tonks, A.J., R.A. Cooper, K.P. Jones, S. Blair, 29. Ndayisaba, G., L. Bazira, E. Habonimana and J. Parton and A. Tonks, 2003. Honey stimulates D. Muteganya, 1993. Clinical and bacteriological inflammatory cytokine production from Monocytes. results in wounds treated with honey. J. Orthop Sug., Cytokine, 21: 242-7. 7(2): 202-204. 21. Abuharfeil,N, R. Al-Oran andm. Abo-Shehada, 1999. The effect of bee honey on proliferative activity of human B and T lymphocytes and the activity of phagocytes. Food AgriImmunol, 11:169-77. 40