Growth hormone modulates the inflammatory and apoptotic pathways incorporated in fluorouracil-induced oral mucositis in rats

Serwi, Rasha H. Al; Darwish, Samar F.; Mahran, Yasmen F.

doi:10.21608/edj.2020.77550

Cited by 14 publications

(5 citation statements)

References 33 publications

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“…Our results confirmed the previous studies, which reported that 5‐FU caused marked loss of body mass and intestinal inflammation. [ 46–48 ] The present work revealed a significant correction of histopathological changes, improvement of body weight decreases, and reduced water intake induced by 5‐FU upon concurrent treatment with thymol in either dose confirming its protective effect. The dose of 120 mg/kg showed greater protection as revealed by histopathological examination.…”

Section: Discussionsupporting

confidence: 72%

Thymol ameliorates 5‐fluorouracil‐induced intestinal mucositis: Evidence of down‐regulatory effect on TGF‐β/MAPK pathways through NF‐κB

Al-Khrashi

Badr

Al-Amin

et al. 2021

J Biochem & Molecular Tox

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5-Fluorouracil (5-FU) is a front-line cytotoxic therapy. However, intestinal mucositis is a well-known adverse event of 5-FU, which limits its therapeutic use. Indeed, thymol, which is a monoterpene component of the essential oil derived from thymus, has a potential anti-inflammatory and immunomodulatory activity. Therefore, this study aimed to investigate the potential chemoprotective effect of thymol against 5-FU-induced intestinal mucositis. Rats were either exposed to two doses of 5-FU (150 mg/kg, ip) and/or treated with thymol (60 or 120 mg/kg). Oxidative stress and inflammatory markers, as well as pathological changes, were assessed. 5-FU-induced severe intestinal damages as were evidenced by histopathological changes as well as oxidative and inflammatory responses. Thymol pretreatment inhibited 5-FU-induced oxidative stress by reducing lipid peroxidation and increasing intestinal levels of antioxidant systems. Moreover, inflammatory response markers, such as interleukin-6, prostaglandin E2, and COX-2 were also improved. The immunoblotting analysis also showed that thymol significantly inhibited the 5-FU-induced expression of nuclear factor-κB, tumor necrosis factor-α, and transforming growth factor β-1 (TGF-β1), in addition to the suppression of p38 and phosphorylated c-Jun N-terminal kinases (p-JNK) mitogen-activated protein kinase proteins' expressions. Our study is the first to demonstrate the promising protective effect of thymol against 5-FUinduced intestinal mucositis through inhibition of oxidative, inflammatory pathways, and suppression of TGF-β/p38/p-JNK signaling.

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Section: Discussionsupporting

confidence: 72%

Thymol ameliorates 5‐fluorouracil‐induced intestinal mucositis: Evidence of down‐regulatory effect on TGF‐β/MAPK pathways through NF‐κB

Al-Khrashi

Badr

Al-Amin

et al. 2021

J Biochem & Molecular Tox

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“…The oral mucosa is particularly sensitive to anticancer treatment [14]. Chemoradiotherapyinduced OM has direct DNA strand breaks localized in the basal epithelium, thus resulting in the release of reactive oxygen species, causing direct damage to mucosal cells [20].…”

Section: Incidence and Pathophysiology Of Chemoradiotherapy-induced O...mentioning

confidence: 99%

Oral Mucositis Induced by Chemoradiotherapy in Head and Neck Cancer—A Short Review about the Therapeutic Management and the Benefits of Bee Honey

et al. 2022

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Background and Objectives: Oral mucositis, a severe non-hematological complication, can be induced by chemoradiotherapy. It is associated with severe local dysfunction, severely affecting the patient’s quality of life; it increases the risk of oral infections and interrupts oncological treatment, thus prolonging the duration and cost of hospitalization. Besides all of the agents used in the prevention and treatment of oral mucositis induced by oncological treatment, can there be found an easier one to administer, with an effective preparation, high addressability, both for adults and paediatric patients, without side effects, and at the same time cheap and easy to purchase? The aim of the present paper is to demonstrate the existence of this product, which is available to everyone, having multiple benefits. Materials and Methods: For the purpose of writing this article, materials were searched in electronic databases in between 2019 and 2021, taking into consideration papers where authors have demonstrated the effectiveness of this product through its topical or systemic use. Results: Numerous studies have highlighted the benefits of honey on oral mucositis. Through its analgesic, anti-inflammatory, anti-cancerous and antibacterial action, honey has proved to have a major impact on the patient’s quality of life and nutritional status by promoting tissue epithelialization and healing of the chemoradiotherapy-induced lesions. Conclusions: Superior to many natural agents, bee honey can be successfully used in both preventing and treating oral mucositis. There are currently numerous studies supporting and recommending the use of bee honey in the management of this oncological toxicity.

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“…Upon its administration, patients may suffer from oral mucositis and IM as a drawback, worsening patients' life quality. This could lead to the discontinuation of the chemotherapy [2,21].…”

Section: Discussionmentioning

confidence: 99%

IL-17/Notch1/STAT3 Pathway Contributes to 5-Fluorouracil-Induced Intestinal Mucositis in Rats: Amelioration by Thymol Treatment

et al. 2022

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5-Fluorouracil (5-FU) is an anticancer drug with intestinal mucositis (IM) as a deleterious side effect. Thymol is a monoterpene phenol which has been reported to possess an antioxidant and anti-inflammatory activity versus 5-FU-induced IM. The Notch pathway affects multiple cellular activities, such as cellular proliferation, in addition to inflammatory responses modulation. Accordingly, this work was carried out in order to elucidate the role of the Notch pathway in 5-FU-induced IM and to further elucidate the immunomodulatory protective mechanisms of thymol. Experimental rats were divided randomly into four groups: Control, 5-FU, 5-FU+thymol (60 mg/kg/day), and 5-FU+thymol (120 mg/kg/day). 5-FU was injected intraperitoneally at a dose of 150 mg/kg on days 6 and 7, while thymol was orally administered daily for 11 days. By the end of the study, intestinal tissues were collected for the determination of IL-17, CD4, CD8, Notch1, Hes-1, pSTAT3, and STAT-3 protein expressions. The effect of thymol on 5-FU cytotoxicity was also examined using WST1 assay. 5-FU induced a marked increase in IL-17 levels, along with a marked downregulation of CD4 and the upregulation of CD8, Notch1, Hes-1 protein expressions, and activation of STAT3 in the intestinal tissue when compared with the control group. Thymol ameliorated the changes that occurred in these parameters. Additionally, cytotoxicity testing revealed that thymol augmented the antiproliferative action of 5-FU against breast and colorectal human cancer cell lines. This study was the first to show that the IL-17/Notch1/STAT3 pathway is involved in the molecular mechanism of 5-FU-induced IM, as well as the immunomodulatory activity of thymol.

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Growth hormone modulates the inflammatory and apoptotic pathways incorporated in fluorouracil-induced oral mucositis in rats

Cited by 14 publications

References 33 publications

Thymol ameliorates 5‐fluorouracil‐induced intestinal mucositis: Evidence of down‐regulatory effect on TGF‐β/MAPK pathways through NF‐κB

Thymol ameliorates 5‐fluorouracil‐induced intestinal mucositis: Evidence of down‐regulatory effect on TGF‐β/MAPK pathways through NF‐κB

Oral Mucositis Induced by Chemoradiotherapy in Head and Neck Cancer—A Short Review about the Therapeutic Management and the Benefits of Bee Honey

IL-17/Notch1/STAT3 Pathway Contributes to 5-Fluorouracil-Induced Intestinal Mucositis in Rats: Amelioration by Thymol Treatment

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