Chemotherapy-induced oral complications significantly affect patient quality of life. 5-Fluorouracil (5-FU), a commonly used chemotherapeutic agent, being particularly associated with mucosal toxicity. This study aimed to evaluate the histological and Histomorphometrical effects of Sidr honey and Moringa oleifera on chemotherapy-induced oral mucosal damage in a rat model. Eighteen male albino rats were divided into three groups: control, 5-FU only, and 5-FU combined with Moringa oleifera and Sidr honey. Tongue tissues were harvested at 14 and 28 days for histological examination and histomorphometric analysis using H&E staining and ImageJ software, with statistical analysis performed via one-way ANOVA and paired t-tests (p<0.05). Results indicated that the 5-FU-only group exhibited progressive epithelial thinning, loss of rete pegs, and increased inflammatory infiltration, while the group receiving Moringa oleifera and Sidr honey showed significant epithelial regeneration, including increased thickness, intact keratinized surfaces, and partial restoration of rete pegs. Statistically significant differences in epithelial thickness were observed across all groups at both time points (p<0.001). Within-group analysis indicated improvements in both the control and treatment groups, whereas a decline was noted in the 5-FU-only group over time. These findings suggest that Moringa oleifera and Sidr honey possess protective and restorative properties against 5-FU-induced lingual mucosal damage, enhancing epithelial regeneration and reducing inflammation. Future research should focus on clinical trials to validate their therapeutic potential in human patients, explore the underlying molecular mechanisms of their protective action.
This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Cancer is one of the leading causes of morbidity and mortality worldwide, ranking second only to cardiovascular diseases. According to global statistics, approximately 19.3 million new cancer cases and 10 million cancer-related deaths were recorded in 2020, with projections indicating a continued rise in incidence over the coming decades
[1]
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018, 68(1), 7-30.
Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024, 74, 229-263.
. A variety of therapeutic modalities are employed in the management of cancer, including surgery, radiotherapy, targeted therapy, immunotherapy, and chemotherapy. Among these, chemotherapy remains a cornerstone of treatment for many solid and hematological malignancies due to its systemic action and efficacy against rapidly dividing cells.
Despite its clinical effectiveness, chemotherapy is associated with a range of adverse effects, which can severely compromise patients’ quality of life. The cytotoxic nature of chemotherapeutic agents results in damage not only to malignant cells but also to healthy, fast-dividing cells, including those lining the gastrointestinal tract and oral mucosa
[3]
Sun Y, Liu Y, Ma X, Hu H. The influence of cell cycle regulation on chemotherapy. Int J Mol Sci. 2021, 22(13), 6923.
. One of the most common and distressing oral complications is oral mucositis, characterized by inflammation, ulceration, and atrophy of the oral epithelium, particularly affecting sensitive structures such as the tongue papillae. These lesions are often painful, interfere with eating and speaking, and may lead to malnutrition, weight loss, increased risk of infection, and treatment delays
[4]
de Miranda JAL, Barreto JEF, Martins DS, de Souza Pimentel PV, Da Silva Costa DV, Silva RR, et al. Protective effect of cashew gum (Anacardium occidentale L.) on 5-fluorouracil-induced intestinal mucositis. Pharmaceuticals. 2019, 12(1), 51.
5-Fluorouracil (5-FU), a pyrimidine analog, is one of the most widely used chemotherapeutic agents. It interferes with DNA synthesis by inhibiting thymidylate synthase, resulting in cell cycle arrest and apoptosis in rapidly proliferating tissues. While 5-FU is recognized for its efficacy in treating various cancers, including colorectal, head and neck, breast, and gastrointestinal tumors, it is also notorious for inducing severe mucosal toxicity, particularly in the oral cavity
[4]
de Miranda JAL, Barreto JEF, Martins DS, de Souza Pimentel PV, Da Silva Costa DV, Silva RR, et al. Protective effect of cashew gum (Anacardium occidentale L.) on 5-fluorouracil-induced intestinal mucositis. Pharmaceuticals. 2019, 12(1), 51.
. The World Health Organization lists 5-FU as an essential medicine due to its clinical utility and cost-effectiveness, making it especially prevalent in developing and resource-limited healthcare settings
[6]
Sharma S. Effects of chemotherapy on oral mucosa. J Academy Dent Educ 2020; 6(1 & 2): 11-5.
The oral side effects of 5-FU, including atrophy of the tongue papillae, significantly hinder patient tolerance to therapy and compromise the overall treatment experience. Managing these complications effectively is crucial to maintaining nutritional status, improving patient compliance, and enhancing clinical outcomes. While various pharmacological interventions have been proposed, their effectiveness remains limited, and many are costly or inaccessible in low-income regions. As a result, there is growing interest in identifying natural, affordable, and effective alternatives that can protect or repair chemotherapy-damaged tissues.
Natural substances with anti-inflammatory, antioxidant, and antimicrobial properties have been increasingly explored for their role in mitigating chemotherapy-induced tissue damage. Among these, Moringa oleifera and Sidr honey have gained considerable attention. Moringa oleifera, often referred to as the “miracle tree,” is a plant native to South Asia and widely used in traditional medicine. Its leaves contain a rich array of bioactive compounds, including vitamins A, C, and E, polyphenols, flavonoids, and essential minerals, which contribute to its potent anti-inflammatory and antioxidant effects
[7]
Zhang QY, Wang FX, Jia KK, Kong LD. Natural product interventions for chemotherapy and radiotherapy-induced side effects. Front Pharmacol. 2018, 9, 1253.
Mikkili I, Suluvoy JK, Thathapudi JJ, et al. Synergistic strategies for cancer treatment: leveraging natural products, drug repurposing and molecular targets for integrated therapy. Beni-Suef Univ J Basic Appl Sci. 2024, 13, 96.
. These properties make it a promising candidate for reducing oxidative stress and inflammation in damaged mucosal tissues.
Similarly, Sidr honey, produced by bees from the nectar of the Ziziphus spina-Christi tree, is known for its wound-healing, antibacterial, and anti-inflammatory properties. It has been used in traditional medicine for centuries and has demonstrated efficacy in promoting tissue regeneration, enhancing epithelial repair, and modulating immune responses in various clinical contexts
[10]
El-Said K, El-Feki S. Therapeutic, chemo-sensitizing, protective effects of natural products against cancerous cells: Preclinical and clinical studies. Biol Biomed J. 2024, 2(2), 1-12.
Pareek A, Pant M, Gupta MM, et al. Moringa oleifera: An updated comprehensive review of its pharmacological activities, ethnomedicinal, phytopharmaceutical formulation, clinical, phytochemical, and toxicological aspects. Int J Mol Sci. 2023, 24(3), 2098.
Ghramh HA, Ibrahim EH, Kilany M. Study of anticancer, antimicrobial, immunomodulatory, and silver nanoparticles production by Sidr honey from three different sources. Food Sci Nutr. 2019, 8(1), 445-455.
Although the individual benefits of Moringa oleifera and Sidr honey have been documented, there is limited research on their combined effect, particularly in the context of oral mucosal damage induced by chemotherapy. Given their distinct but potentially synergistic mechanisms of action, the combination of these two natural products may offer enhanced protection and tissue regeneration in the oral cavity during chemotherapy. Exploring such combinations could lead to the development of low-cost, accessible therapeutic options, especially for use in countries where access to advanced oral care is limited.
This study aims to address this gap by investigating the histological and Histomorphometrical changes in the tongue papillae of rats subjected to 5-FU chemotherapy and treated with Moringa oleifera and Sidr honey. Through quantitative and qualitative tissue analysis, this research seeks to provide evidence for the potential protective and reparative effects of these natural agents on oral tissues compromised by chemotherapy.
2. Materials and Methods
2.1. Sample Size Calculation
Sample size calculation was performed using G*Power version 3.1.9.2, Faul et al, [2007 & 2013] University Kiel, Germany. Copyright (c) 1992-2014.
[13]
Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007, 39(2), 175-191.
Where: F: is the effect size; α= 0.05; β= 0.05; Power= 1- β = 0.80 (80%).
The effect size f was 0.82 using alpha (α) level of 0.05 and Beta (β) level of 0.05, i.e., power = 80%; the estimated sample size (n) should be at least 18 samples (Rats). The sample size in this study agrees with Eltokhey et al., 2013 who have published on this point
[14]
Faul F, Erdfelder E, Buchner A, Lang AG. G*Power Version 3.1.7 [computer software]. Universität Kiel, Germany. 2013. Available from:
1) Adrucil® (fluorouracil injection USP), purchased from a local pharmacy.
2) Moringa oleifera Leaf Powder: Fresh leaves of moringa (Moringa oleifera) were collected from the local market. The leaves were removed from the stems, washed several times with distilled water, and then air-dried at room temperature for one to two days. The leaves were then ground into a homogeneous powder when they were completely dried.
3) Sidr Honey: Sidr honey was sourced directly from local Libyan beekeepers.
2.3. Animals
Eighteen male albino rats, each weighing between 220 and 250 grammes, were used in this study. The experiment was conducted in the animal house, Faculty of Medicine, University of Benghazi. An approval for the experimental animal was given by the Scientific Research Ethical Committee (SREC) of the Faculty of Dentistry, University of Benghazi (Approval No: 0277).
The rats were maintained under standard laboratory conditions, housed in separate cages accommodating three rats each. The room temperature was kept between 20 and 25°C, and the rats were provided with a standard diet along with unrestricted access to water.
Rats were randomly divided into:
Group I: Control group which did not receive any treatment.
Group II: Chemotherapy group (which was administered with chemotherapy).
Group III: Chemotherapy group (which was administered with chemotherapy) and treated with Sidr honey and Moringa Oleifera.
Each group consisted of 6 rats and was further divided into two subgroups based on the treatment duration:
1: After 14 days; 2: After 28 days.
2.4. Induction of Chemotherapy
Treated animals received 5-FU (fluorouracil; 50 mg/mL - Adrucil®) intraperitoneally on the first 4 days at 15 mg/kg/day (equivalent in humans), and the next 4 alternate days at 6 mg/kg/day. The 15 mg/kg dose was given on the 14th day of treatment
[15]
da Silva MC, Fabiano LC, da Costa Salomão KC, de Freitas PLZ, Neves CQ, Borges SC, et al. A rodent model of human-dose equivalent 5-fluorouracil: toxicity in the liver, kidneys, and lungs. Antioxidants. 2023, 12(5), 1005.
The treatment groups received Sidr honey mixed with Moringa Oleifera powder orally, starting from the first day of chemotherapy and continuing for an additional 14 days post-chemotherapy.
2.6. Histological and Histomorphometrical Analysis
At the end of the experiment, all rats were euthanized by anesthetic overdose of thiopental. Rats’ tongues were dissected and preserved. The specimens were processed to be stained by hematoxylin and eosin (H&E) to detect the histological changes
[16]
Bancroft JD, Gamble M. Theory and practice of histological techniques. 6th ed. Philadelphia: Churchill Livingstone; 2008. p. 6-127.
[16]
.
Histomorphometrical analysis was conducted using the ImageJ 1.53 K application (source: NIH, USA; open-source application available at https://imagej.nih.gov/ij/download.html) for measurement of the thickness in the tissue on the slide.
2.7. Statistical Analysis
Data collected were analyzed using appropriate statistical methods, including one-way ANOVA for comparison between groups, followed by post-hoc analysis where applicable also, paired samples T test was used to compare Day 14 with Day 28 in each group. A p-value of <0.05 will be considered statistically significant. All analyses were performed using SPSS software.
3. Results
3.1. Histological Results
The samples were studied with a histological approach at two points, 14 days and 28 days post-treatment, to find out how the keratinized stratified squamous epithelium changed in each of the experimental groups.
Figure 1. A photomicrograph of a tongue from group I shows that it is covered by normal thickness of stratified squamous epithelium of filiform papillae with regular rete pegs (H&EX100).
By the end of 14 days, the tissue in the control group was covered by keratinized stratified squamous epithelium of filiform papillae of normal thickness with regular and uniform rete pegs [Figure 1]. In contrast, Group II had keratinized stratified squamous epithelium that was shorter, uneven, and devoid of rete pegs. The epithelial cells had shedded. The lamina propria showed obvious signs of inflammatory cell infiltration [Figure 2].
Figure 2. A photomicrograph of a tongue from group II shows that the keratinized stratified squamous epithelium of filiform papillae appeared shorter, irregular with loss of rete pegs. Increase the numbers of inflammatory cells in lamina propria (H&EX100).
Unlike Group II, the epithelium in Group III were more complex. Some sections of the keratinized stratified squamous epithelium showed a greater thickness which also had irregular rete pegs present. In particular, there was no change in the keratinized surface [Figure 3].
Figure 3. A photomicrograph of a tongue from group III shows that the thickness of keratinized stratified squamous epithelium was increased with irregular rete pegs in some areas. The keratinized surface appeared undamaged. (H&EX100).
3.1.2. Day 28 Observation
On evaluating the tissues at 28 days, the control group demonstrated that the filiform papillae were covered by keratinized stratified squamous epithelium of normal thickness, featuring regular and uniform rete pegs [Figure 4].
Figure 4. A photomicrograph of a tongue from group I shows that it is covered by normal thickness of stratified squamous epithelium of filiform papillae with regular rete pegs (H&EX100).
On the other hand, Group II had keratinized stratified squamous epithelium that appeared more irregular, shorter, and uneven, with more destruction of rete pegs as compared with day 14. The epithelial cells had a shed and keratin layer destructed in some areas. The lamina propria showed more inflammatory cell infiltration [Figure 5].
Figure 5. A photomicrograph of a tongue from group II shows that the keratinized stratified squamous epithelium appeared more irregular, shorter, uneven, and more destruction of rete pegs as compared with day 14. More inflammatory cells in lamina propria (H&EX100).
Conversely, Group III displayed remarkable improvement in epithelial features after 28 days. Notably, the epithelial layer was increased and revealed unevenly located rete pegs in a few areas. Moreover, the keratin layer was thicker compared to the previous assessment [Figure 6].
Figure 6. A photomicrograph of a tongue from group III shows that the thickness of epithelium increased with uneven rete pegs. Undamaged keratinized surface was also seen with more keratin as compared with day 14 (H&EX100).
3.2. Statistical Analysis
The table presents the comparison of thickness of epithelium among groups (GI, GII, GIII) at 14 and 28 days. At both 14 and 28 days, there were statistically significant differences in thickness of epithelium among the groups (P < 0.001 for both time points). Specifically, GIII consistently showed the highest mean thickness, followed by GI, while GII had the lowest mean thickness at both time points. When comparing within each group over time, GI and GIII showed a significant increase in thickness from 14 to 28 days (P = 0.008 and P = 0.010, respectively), while GII experienced a significant decrease in thickness from 14 to 28 days (P = 0.045). The pairwise comparison indicates significant differences between groups within each time point based on post-hoc analysis [Table 1], [Figure 7].
Table 1. Comparison of epithelium thickness between groups at 14 and 28 days.
14 days
28 days
P value
Mean
SD
Mean
SD
GI
11.62 b
0.78
14.24 b
0.52
0.008**
GII
8.50 c
0.55
5.50 c
0.61
0.045*
GIII
16.89 a
0.34
21.17 a
0.42
0.010**
P value
<0.001**
<0.001**
*and**; means significant at P<0.05 and <0.001 respectively.
Figure 7. A graph shows Comparison of epithelium thickness between groups at 14 and 28 days.
4. Discussion
Cancer remains a major global public health burden, accounting for nearly 10 million deaths in 2020, or nearly one in six deaths. Chemotherapy remains an essential component of cancer treatment protocols due to its systemic efficacy against rapidly proliferating malignant cells. However, its non-selective cytotoxicity often results in adverse effects on normal tissues, particularly the mucosa, thereby compromising patient quality of life
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Doostmohammadi A, Jooya H, Ghorbanian K, et al. Potentials and future perspectives of multi-target drugs in cancer treatment: the next generation anti-cancer agents. Cell Commun Signal. 2024, 22, 228.
Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide. CA Cancer J Clin. 2021, 71(3), 209-249.
Sonis ST. Oral mucositis in cancer therapy. J Support Oncol. 2004 Nov-Dec; 2(6 Suppl 3): 3-8. PMID: 15605918.
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. Managing these side effects is crucial not only for patient comfort but also for treatment adherence and overall clinical outcomes.
5-Fluorouracil (5-FU) is one of the most commonly used chemotherapeutic agents and has been included in the World Health Organization’s list of essential medicines due to its broad-spectrum efficacy and affordability, especially in developing countries
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World Health Organization (WHO). Model list of essential medicines. 2021. Available from:
. Despite its clinical benefits, 5-FU is associated with significant oral complications, including mucositis and atrophy of the tongue papillae, which result from epithelial damage and inflammation
[21]
Elting LS, Cooksley C, Chambers M, Cantor SB, Manzullo E, Rubenstein EB. The burdens of cancer therapy: clinical and economic outcomes of chemotherapy-induced mucositis. Cancer. 2003, 98(7), 1531-1539.
Al-Hashimi I, Sonis ST, Peterson DE. Oral mucositis in cancer patients: a review. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007, 103(1), S20. e1-S20. e13.
The present study investigated the potential protective and regenerative effects of Moringa oleifera and Sidr honey on 5-FU-induced tongue epithelial damage in a rat model. After 14 days, the control group exhibited histologically normal, well-organized keratinized stratified squamous epithelium with intact rete pegs, consistent with previous studies that confirm the structural resilience of oral mucosa in the absence of cytotoxic stress
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Greenberg MS, Glick M. Burket’s oral medicine. 12th ed. Hamilton: BC Decker; 2015.
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Carvalho PT, de Souza PL, de Almeida JR, et al. 5-FU-induced oral mucositis in rats: preventive strategies. Support Care Cancer. 2012, 20(11), 2791-2798.
. In contrast, Group II (5-FU only) showed marked epithelial thinning, loss of rete pegs, and inflammatory cell infiltration, which align with documented mucotoxic effects of fluorouracil in both animal models and human studies
[26]
Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005, 55(2), 74-108.
Interestingly, rats in Group III, treated with both Moringa oleifera and Sidr honey, exhibited significantly improved epithelial thickness by day 14. This suggests a protective and reparative role for these natural substances. The antioxidant and anti-inflammatory properties of Moringa oleifera, derived from its high content of polyphenols, flavonoids, and vitamins, have been shown to promote tissue regeneration and modulate immune responses
[10]
El-Said K, El-Feki S. Therapeutic, chemo-sensitizing, protective effects of natural products against cancerous cells: Preclinical and clinical studies. Biol Biomed J. 2024, 2(2), 1-12.
At 28 days post-treatment, histological differences became more pronounced. The control group retained normal mucosal structure, while the chemotherapy group showed progressive tissue deterioration, including further destruction of rete pegs and increased inflammatory infiltration. This finding is consistent with the known cumulative cytotoxicity of 5-FU, which induces DNA synthesis inhibition and epithelial cell apoptosis
[30]
Abou El-Nour MM, El-Kased RF, El-Mahdy MA, et al. Moringa and honey combination promotes wound healing in diabetic rats. Wound Repair Regen. 2020, 28(3), 386-396.
. Conversely, Group III showed a marked recovery of epithelial features, including increased thickness, partial restoration of rete pegs, and a thicker keratin layer, indicating ongoing epithelial regeneration and long-term tissue remodeling.
The statistical findings further reinforce the histological observations. Group III consistently exhibited the highest epithelial thickness at both 14 and 28 days, while Group II had the lowest. Significant increases in epithelial thickness were noted from day 14 to day 28 in Groups I and III (p = 0.008 and p = 0.010, respectively), whereas Group II showed a significant decrease (p = 0.045). These results clearly support the protective role of Moringa oleifera and Sidr honey and highlight their potential as adjuncts in managing chemotherapy-induced oral complications.
4.1. Study Limitations
While the findings are promising, several limitations must be acknowledged. First, the study was conducted on a small animal sample, and extrapolation to human physiology should be made cautiously. Second, the study focused primarily on histological and morphometric analysis; inclusion of biochemical and molecular data (e.g., inflammatory cytokines, oxidative stress markers) would provide a more comprehensive understanding of the mechanisms involved. Lastly, the dosage and administration of Moringa oleifera and Sidr honey were tailored to experimental conditions and may require further standardization and safety evaluation for clinical application.
4.2. Clinical and Research Implications
This study provides preliminary evidence supporting the use of Moringa oleifera and Sidr honey as potential adjunctive therapies for the management of chemotherapy-induced oral mucositis. Given their natural origin, accessibility, and affordability, they are especially suitable for use in resource-constrained healthcare settings. Their integration into supportive care protocols could offer a safe, low-cost, and effective strategy to minimize oral complications, enhance mucosal healing, and improve overall quality of life for cancer patients. Future randomized controlled trials in humans, along with detailed pharmacological studies, are essential to validate these findings and establish standardized dosing guidelines.
4.3. Conclusion
In conclusion, this study demonstrated that Moringa oleifera and Sidr honey have significant protective and regenerative effects on 5-FU-induced epithelial damage in the tongue papillae of rats. Their use was associated with improved epithelial thickness, reduced inflammation, and partial restoration of mucosal integrity. These findings suggest that these natural agents may be valuable adjuncts in supportive cancer care, particularly in the management of oral complications caused by chemotherapy. Future research should focus on clarifying the molecular mechanisms by which Sidr honey and Moringa oleifera exert their protective effects against chemotherapy-induced oral mucositis. Given the promising results in this rat model, clinical trials are necessary to confirm the potential synergistic effects of these natural agents against mucositis, which significantly enhance patient care.
Abbreviations
5-FU
5-Fluorouracil
DNA
Deoxyribonucleic Acid
Author Contributions
Fatema Elturki: Writing - original draft, Supervision
Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024, 74, 229-263.
de Miranda JAL, Barreto JEF, Martins DS, de Souza Pimentel PV, Da Silva Costa DV, Silva RR, et al. Protective effect of cashew gum (Anacardium occidentale L.) on 5-fluorouracil-induced intestinal mucositis. Pharmaceuticals. 2019, 12(1), 51.
Zhang QY, Wang FX, Jia KK, Kong LD. Natural product interventions for chemotherapy and radiotherapy-induced side effects. Front Pharmacol. 2018, 9, 1253.
Mikkili I, Suluvoy JK, Thathapudi JJ, et al. Synergistic strategies for cancer treatment: leveraging natural products, drug repurposing and molecular targets for integrated therapy. Beni-Suef Univ J Basic Appl Sci. 2024, 13, 96.
El-Said K, El-Feki S. Therapeutic, chemo-sensitizing, protective effects of natural products against cancerous cells: Preclinical and clinical studies. Biol Biomed J. 2024, 2(2), 1-12.
Pareek A, Pant M, Gupta MM, et al. Moringa oleifera: An updated comprehensive review of its pharmacological activities, ethnomedicinal, phytopharmaceutical formulation, clinical, phytochemical, and toxicological aspects. Int J Mol Sci. 2023, 24(3), 2098.
Ghramh HA, Ibrahim EH, Kilany M. Study of anticancer, antimicrobial, immunomodulatory, and silver nanoparticles production by Sidr honey from three different sources. Food Sci Nutr. 2019, 8(1), 445-455.
Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007, 39(2), 175-191.
da Silva MC, Fabiano LC, da Costa Salomão KC, de Freitas PLZ, Neves CQ, Borges SC, et al. A rodent model of human-dose equivalent 5-fluorouracil: toxicity in the liver, kidneys, and lungs. Antioxidants. 2023, 12(5), 1005.
Bancroft JD, Gamble M. Theory and practice of histological techniques. 6th ed. Philadelphia: Churchill Livingstone; 2008. p. 6-127.
[17]
Doostmohammadi A, Jooya H, Ghorbanian K, et al. Potentials and future perspectives of multi-target drugs in cancer treatment: the next generation anti-cancer agents. Cell Commun Signal. 2024, 22, 228.
Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide. CA Cancer J Clin. 2021, 71(3), 209-249.
Elting LS, Cooksley C, Chambers M, Cantor SB, Manzullo E, Rubenstein EB. The burdens of cancer therapy: clinical and economic outcomes of chemotherapy-induced mucositis. Cancer. 2003, 98(7), 1531-1539.
Al-Hashimi I, Sonis ST, Peterson DE. Oral mucositis in cancer patients: a review. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007, 103(1), S20. e1-S20. e13.
Carvalho PT, de Souza PL, de Almeida JR, et al. 5-FU-induced oral mucositis in rats: preventive strategies. Support Care Cancer. 2012, 20(11), 2791-2798.
Elturki, F., Gehani, G., Ahmed, K., Salawat, S. (2025). Effect of Sidr Honey and Moringa Oleifera on Chemotherapy-induced Oral Complications: A Histological and Histomorphometrical Study in a Rat Model. American Journal of Clinical and Experimental Medicine, 13(4), 91-98. https://doi.org/10.11648/j.ajcem.20251304.14
Elturki, F.; Gehani, G.; Ahmed, K.; Salawat, S. Effect of Sidr Honey and Moringa Oleifera on Chemotherapy-induced Oral Complications: A Histological and Histomorphometrical Study in a Rat Model. Am. J. Clin. Exp. Med.2025, 13(4), 91-98. doi: 10.11648/j.ajcem.20251304.14
Elturki F, Gehani G, Ahmed K, Salawat S. Effect of Sidr Honey and Moringa Oleifera on Chemotherapy-induced Oral Complications: A Histological and Histomorphometrical Study in a Rat Model. Am J Clin Exp Med. 2025;13(4):91-98. doi: 10.11648/j.ajcem.20251304.14
@article{10.11648/j.ajcem.20251304.14,
author = {Fatema Elturki and Ghada Gehani and Karima Ahmed and Somaya Salawat},
title = {Effect of Sidr Honey and Moringa Oleifera on Chemotherapy-induced Oral Complications: A Histological and Histomorphometrical Study in a Rat Model
},
journal = {American Journal of Clinical and Experimental Medicine},
volume = {13},
number = {4},
pages = {91-98},
doi = {10.11648/j.ajcem.20251304.14},
url = {https://doi.org/10.11648/j.ajcem.20251304.14},
eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajcem.20251304.14},
abstract = {Chemotherapy-induced oral complications significantly affect patient quality of life. 5-Fluorouracil (5-FU), a commonly used chemotherapeutic agent, being particularly associated with mucosal toxicity. This study aimed to evaluate the histological and Histomorphometrical effects of Sidr honey and Moringa oleifera on chemotherapy-induced oral mucosal damage in a rat model. Eighteen male albino rats were divided into three groups: control, 5-FU only, and 5-FU combined with Moringa oleifera and Sidr honey. Tongue tissues were harvested at 14 and 28 days for histological examination and histomorphometric analysis using H&E staining and ImageJ software, with statistical analysis performed via one-way ANOVA and paired t-tests (p<0.05). Results indicated that the 5-FU-only group exhibited progressive epithelial thinning, loss of rete pegs, and increased inflammatory infiltration, while the group receiving Moringa oleifera and Sidr honey showed significant epithelial regeneration, including increased thickness, intact keratinized surfaces, and partial restoration of rete pegs. Statistically significant differences in epithelial thickness were observed across all groups at both time points (p<0.001). Within-group analysis indicated improvements in both the control and treatment groups, whereas a decline was noted in the 5-FU-only group over time. These findings suggest that Moringa oleifera and Sidr honey possess protective and restorative properties against 5-FU-induced lingual mucosal damage, enhancing epithelial regeneration and reducing inflammation. Future research should focus on clinical trials to validate their therapeutic potential in human patients, explore the underlying molecular mechanisms of their protective action.},
year = {2025}
}
TY - JOUR
T1 - Effect of Sidr Honey and Moringa Oleifera on Chemotherapy-induced Oral Complications: A Histological and Histomorphometrical Study in a Rat Model
AU - Fatema Elturki
AU - Ghada Gehani
AU - Karima Ahmed
AU - Somaya Salawat
Y1 - 2025/08/16
PY - 2025
N1 - https://doi.org/10.11648/j.ajcem.20251304.14
DO - 10.11648/j.ajcem.20251304.14
T2 - American Journal of Clinical and Experimental Medicine
JF - American Journal of Clinical and Experimental Medicine
JO - American Journal of Clinical and Experimental Medicine
SP - 91
EP - 98
PB - Science Publishing Group
SN - 2330-8133
UR - https://doi.org/10.11648/j.ajcem.20251304.14
AB - Chemotherapy-induced oral complications significantly affect patient quality of life. 5-Fluorouracil (5-FU), a commonly used chemotherapeutic agent, being particularly associated with mucosal toxicity. This study aimed to evaluate the histological and Histomorphometrical effects of Sidr honey and Moringa oleifera on chemotherapy-induced oral mucosal damage in a rat model. Eighteen male albino rats were divided into three groups: control, 5-FU only, and 5-FU combined with Moringa oleifera and Sidr honey. Tongue tissues were harvested at 14 and 28 days for histological examination and histomorphometric analysis using H&E staining and ImageJ software, with statistical analysis performed via one-way ANOVA and paired t-tests (p<0.05). Results indicated that the 5-FU-only group exhibited progressive epithelial thinning, loss of rete pegs, and increased inflammatory infiltration, while the group receiving Moringa oleifera and Sidr honey showed significant epithelial regeneration, including increased thickness, intact keratinized surfaces, and partial restoration of rete pegs. Statistically significant differences in epithelial thickness were observed across all groups at both time points (p<0.001). Within-group analysis indicated improvements in both the control and treatment groups, whereas a decline was noted in the 5-FU-only group over time. These findings suggest that Moringa oleifera and Sidr honey possess protective and restorative properties against 5-FU-induced lingual mucosal damage, enhancing epithelial regeneration and reducing inflammation. Future research should focus on clinical trials to validate their therapeutic potential in human patients, explore the underlying molecular mechanisms of their protective action.
VL - 13
IS - 4
ER -
Elturki, F., Gehani, G., Ahmed, K., Salawat, S. (2025). Effect of Sidr Honey and Moringa Oleifera on Chemotherapy-induced Oral Complications: A Histological and Histomorphometrical Study in a Rat Model. American Journal of Clinical and Experimental Medicine, 13(4), 91-98. https://doi.org/10.11648/j.ajcem.20251304.14
Elturki, F.; Gehani, G.; Ahmed, K.; Salawat, S. Effect of Sidr Honey and Moringa Oleifera on Chemotherapy-induced Oral Complications: A Histological and Histomorphometrical Study in a Rat Model. Am. J. Clin. Exp. Med.2025, 13(4), 91-98. doi: 10.11648/j.ajcem.20251304.14
Elturki F, Gehani G, Ahmed K, Salawat S. Effect of Sidr Honey and Moringa Oleifera on Chemotherapy-induced Oral Complications: A Histological and Histomorphometrical Study in a Rat Model. Am J Clin Exp Med. 2025;13(4):91-98. doi: 10.11648/j.ajcem.20251304.14
@article{10.11648/j.ajcem.20251304.14,
author = {Fatema Elturki and Ghada Gehani and Karima Ahmed and Somaya Salawat},
title = {Effect of Sidr Honey and Moringa Oleifera on Chemotherapy-induced Oral Complications: A Histological and Histomorphometrical Study in a Rat Model
},
journal = {American Journal of Clinical and Experimental Medicine},
volume = {13},
number = {4},
pages = {91-98},
doi = {10.11648/j.ajcem.20251304.14},
url = {https://doi.org/10.11648/j.ajcem.20251304.14},
eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajcem.20251304.14},
abstract = {Chemotherapy-induced oral complications significantly affect patient quality of life. 5-Fluorouracil (5-FU), a commonly used chemotherapeutic agent, being particularly associated with mucosal toxicity. This study aimed to evaluate the histological and Histomorphometrical effects of Sidr honey and Moringa oleifera on chemotherapy-induced oral mucosal damage in a rat model. Eighteen male albino rats were divided into three groups: control, 5-FU only, and 5-FU combined with Moringa oleifera and Sidr honey. Tongue tissues were harvested at 14 and 28 days for histological examination and histomorphometric analysis using H&E staining and ImageJ software, with statistical analysis performed via one-way ANOVA and paired t-tests (p<0.05). Results indicated that the 5-FU-only group exhibited progressive epithelial thinning, loss of rete pegs, and increased inflammatory infiltration, while the group receiving Moringa oleifera and Sidr honey showed significant epithelial regeneration, including increased thickness, intact keratinized surfaces, and partial restoration of rete pegs. Statistically significant differences in epithelial thickness were observed across all groups at both time points (p<0.001). Within-group analysis indicated improvements in both the control and treatment groups, whereas a decline was noted in the 5-FU-only group over time. These findings suggest that Moringa oleifera and Sidr honey possess protective and restorative properties against 5-FU-induced lingual mucosal damage, enhancing epithelial regeneration and reducing inflammation. Future research should focus on clinical trials to validate their therapeutic potential in human patients, explore the underlying molecular mechanisms of their protective action.},
year = {2025}
}
TY - JOUR
T1 - Effect of Sidr Honey and Moringa Oleifera on Chemotherapy-induced Oral Complications: A Histological and Histomorphometrical Study in a Rat Model
AU - Fatema Elturki
AU - Ghada Gehani
AU - Karima Ahmed
AU - Somaya Salawat
Y1 - 2025/08/16
PY - 2025
N1 - https://doi.org/10.11648/j.ajcem.20251304.14
DO - 10.11648/j.ajcem.20251304.14
T2 - American Journal of Clinical and Experimental Medicine
JF - American Journal of Clinical and Experimental Medicine
JO - American Journal of Clinical and Experimental Medicine
SP - 91
EP - 98
PB - Science Publishing Group
SN - 2330-8133
UR - https://doi.org/10.11648/j.ajcem.20251304.14
AB - Chemotherapy-induced oral complications significantly affect patient quality of life. 5-Fluorouracil (5-FU), a commonly used chemotherapeutic agent, being particularly associated with mucosal toxicity. This study aimed to evaluate the histological and Histomorphometrical effects of Sidr honey and Moringa oleifera on chemotherapy-induced oral mucosal damage in a rat model. Eighteen male albino rats were divided into three groups: control, 5-FU only, and 5-FU combined with Moringa oleifera and Sidr honey. Tongue tissues were harvested at 14 and 28 days for histological examination and histomorphometric analysis using H&E staining and ImageJ software, with statistical analysis performed via one-way ANOVA and paired t-tests (p<0.05). Results indicated that the 5-FU-only group exhibited progressive epithelial thinning, loss of rete pegs, and increased inflammatory infiltration, while the group receiving Moringa oleifera and Sidr honey showed significant epithelial regeneration, including increased thickness, intact keratinized surfaces, and partial restoration of rete pegs. Statistically significant differences in epithelial thickness were observed across all groups at both time points (p<0.001). Within-group analysis indicated improvements in both the control and treatment groups, whereas a decline was noted in the 5-FU-only group over time. These findings suggest that Moringa oleifera and Sidr honey possess protective and restorative properties against 5-FU-induced lingual mucosal damage, enhancing epithelial regeneration and reducing inflammation. Future research should focus on clinical trials to validate their therapeutic potential in human patients, explore the underlying molecular mechanisms of their protective action.
VL - 13
IS - 4
ER -
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