Could Honey Have a Place in Colitis Therapy? Effects of Honey, Prednisolone, and Disulfiram on Inflammation, Nitric Oxide, and Free Radical FormationBilsel Y.a · Bugra D.a · Yamaner S.a · Bulut T.a · Cevikbas U.b · Turkoglu U.c
Departments of aGeneral Surgery, bPathology, and cBiochemistry, Istanbul Medical Faculty, Istanbul, Turkey
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Background/Aims: The purpose of this study was to investigate the potential therapeutic roles of honey, prednisolone and disulfiram in an experimental model of inflammatory bowel disease. Another aspect of the study was to find out whether these substances have any effect on nitric oxide (NO) and free radical production. Methods: After the induction of colitis with trinitrobenzene sulfonic acid in 64 male rats, physiological saline, honey, prednisolone and disulfiram enemas were applied to the rats once daily for 3 days (acute treatment groups) or 7 days (chronic treatment groups). Control groups received only saline enemas. Rats were killed on the 4th or 8th days and their colonic mucosal damage was quantitated using a scoring system. Acute and chronic inflammatory responses were determined by a mucosal injury score, histological examination and measurement of the myeloperoxidase (MPO) activity of tissues. The content of malonylaldehyde (MDA) and NO metabolites in colon homogenates was also measured to assess the effects of these substances on NO and free oxygen radical production. Results: Estimation of colonic damage by mucosal injury scoring was found to be strongly correlated with the histologic evaluation of colon specimens. On the other hand, mucosal injury scores were not correlated with MPO, MDA or NO values. There were significant differences between the MPO results of chronic-control and chronic-honey groups, as well as chronic-control and chronic-prednisolone groups (p = 0.03 and p = 0.0007). The acute honey, prednisolone, and disulfiram groups had significantly lower MDA results compared to the acute control group (p = 0.04, p = 0.02, and p = 0.04). In terms of NO, there was no significant difference between the treatment and control groups. NO was found to have a strong relationship with MDA (p = 0.03) and MPO values (p = 0.001). On the other hand, MPO results were not found to be correlated with MDA values (p > 0.05). Conclusions: MPO activity is not directly proportional to the severity of the inflammation, but it may only determine the amount of neutrophil in the tissues. Inflammatory cells are not the sole intensifying factor in colitis. Therefore, mucosal injury scores may not correlate well with MPO activities. In an inflammatory state NO and MPO levels have a strong relationship, since NO is released from the neutrophils. In an inflammatory model of colitis, intrarectal honey administration is as effective as prednisolone treatment. Honey may have some features in the treatment of colitis, but this issue requires further investigation. Honey, prednisolone and even disulfiram also have some value in preventing the formation of free radicals released from the inflamed tissues. Prednisolone may also have some possible benefits in the inhibition of NO production in colitis therapy.
© 2002 S. Karger AG, Basel
J. Davies, J.R.T. Monson
Academic Surgical Unit, Castle Hill Hospital, Hull, UK
In this edition of the journal Bilsel et al. report their work studying the effect of honey, prednisolone and disulfiram in the trinitrobezene sulfonic acid (TNBS) colitis rat model. They concluded that intra-rectal administration of honey appeared to be as effective a method of treatment as prednisolone.
This ambitious study was well performed, using an established colitis model. Mucosal inflammation was assessed both macroscopically and microscopically, using recognized techniques, by 2 independent observers, in both an acute and chronic colitis model. Myelopreperoxidase (MPO) was used as an index of quantitative inflammation and neutrophil infiltration in the tissue  and it was somewhat surprising these findings did not correlate with the histological results. Honey has known wound-healing, antimicrobial and even tumouricidal properties  some of which have been known since ancient times . The antimicrobial activity of honey has been attributed to the antioxidant properties of hydrogen peroxide . The potential mechanisms by which honey improved colitis were not discussed in the manuscript and obviously further research needs to be done to elucidate the results reported.
Infiltrating neutrophils are believed to play a major pathological role in both clinical and experimental inflammatory bowel disease. The activated neutrophils produce oxygen-derived free radicals, such as superoxide and hydrogen peroxide, which can result in tissue damage. Malondialdehyde (MDA) was used as an indicator of tissue damage, and nitric oxide (NO) metabolites were also measured. Unfortunately the results of the two above assays added little to the overall message.
Prednisolone was superior to all other treatments, in the acute colitis model, based on histology, MPO and NO findings. In the 7-day chronic colitis model honey appeared to be the most effective treatment. It was somewhat surprising that prednisolone seemed ineffective in chronic colitis and further explanation of these findings and the differences between the acute and chronic colitis models should be explored in further work . The authors rightly conclude that further work needs to be done using the TNBS colitis model to identify the mechanism by which honey is effective and perhaps a small clinical pilot study would be helpful. There is little in the world literature regarding the use of disulfiram in experimental colitis, and while it has a known free oxygen radical scavenger role, in the TNBS-colitis model used it appeared to be of limited value.
The use ‘alternative medicine’ is increasingly popular and has encouraged the creation of the National Centre for Complementary and Alternative Medicine (NCCAM) at the National Institute of Health founded for the evaluation of alternative medicine and treatments . The authors quote that the ‘traditional’ treatment for colitis in their country is honey mixed with henna, and perhaps replacing the disulfiram arm with a honey/henna arm would have provided more insight into potential mechanisms. The other implication of these findings is the potential cost saving associated with honey. The discovery of a cheap, simple and widely available treatment for patients with limited inflammatory bowel disease may have important implications to colitis management throughout the world. In both countries where the costs of other recognized treatments are prohibitive, and in countries where patients demand ‘alternative medicine’ equivalents to standard management, honey may well provide a simple solution.References
1 Guo X, Wang WP, Kl JK, Cho CH: Involvement of neutrophils and free radicals in the potentiating effects of passive cigarette smoking on inflammatory bowel disease in rats. Gastroenterology 1999;117:884–892.
2 Hamzaoglu I, Saribeyoglu K, Durak H, Karahasanoglu T, Bayrak I, Altug T, Sirin F, Sariyar M: Protective covering of surgical wounds with honey impedes tumour implantation. Arch Surg 2000;135:1414–1417.
3 Cooper RA, Molan PC, Harding KG: Antibacterial activity of honey against strains of Staphylococcus aureus from infected wounds. J R Soc Med 1999;92:283–285.
4 Taormina PJ, Niemira BA, Beuchat LR: Inhibitory activity of honey against foodborne pathogens as influenced by the presence of hydrogen peroxide and level of antioxidant power. Int J Food Microbiol 2001;69:217–225.
5 Ajuebor MN, Hogaboam CM, Kundel SL, Proudfoot AE, Wallace JL: The chemokine RANTES is a crucial mediator of the progression from acute to chronic colitis in the rat. J Immunol 2001;166:552–558.
6 Nahin RL, Straus SE: Research into complementary and alternative medicine: Problems and potential. BMJ 2001;322:161–164.
Department of Surgery, University of Louisville, Ky., USA
Bilsel et al. present an intriguing concept, i.e., that honey could be used in the treatment of acute colitis. There has been an increasing awareness in the last 10 years of the role of alternative therapy in the treatment of many human diseases. Many countries have their own proven ‘home remedies’, such as mixing honey with henna for colitis in Turkey, as described in this article. German medicine has also for years covered the cost of alternative therapies such as spa treatments for their patients. There is currently an institute in the National Institutes of Health that focuses on alternative treatments.
In many countries where there is no national health insurance, the cost of anti-inflammatory drugs such as 5ASA medicines can be prohibitive. The cost of oral mesalamine, for example, in the United States can exceed USD 3,000/year. The development of effective, more cost conscious and ‘natural treatments’ will surely increase in the next several years. Already in the United States there is a ‘physician’s desk reference’ for herbal medication. While it is very easy to be a skeptic, I applaud the authors for taking a scientific look at a traditional treatment used by the people of their country.
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