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

Abstract

Introduction:Oral mucositis (OM) is a well-known complication of radiotherapy (RT) and chemotherapy (CT) in cancer patients. Although, 5-flourouracil (5-FU) is one of the standard cytotoxic therapies, it is one of the most common causes of OM, which results in delay, dose reduction or treatment discontinuation, thus this intensifies the need for an effective chemoprotective agent. We aimed to investigate the potential chemoprotective effect of growth hormone (GH) on 5-FU-induced OM in rats. Material & Methods:Rats were either exposed to a single 5-FU injection (160 mg/kg ip) and/or treated with GH (1 mg/kg s.c). Oxidative stress, inflammatory and apoptotic markers were assessed.Results: An array of mucosal damage was produced as a result of 5-FU injection, which was evident by histopathology. 5-FU induced a remarkable increase in lipid peroxidation accompanied with a significant depletion of glutathione level. Besides, inflammatory cascades, including NF-κB and IL-6, were elevated significantly. Furthermore, 5-FU stimulated cell death through the significant increase of caspase-3. Interestingly, Pre-treatment with GH markedly ameliorated the deleterious effects of 5-FU through counteracting the oxidative stress and inflammation-mediated apoptosis. In addition, GH rescued the oral mucosal histology following chemotherapy. Conclusions:Our study is the first to demonstrate evidences for the effective chemoprotection provided by GH against 5-FU induced OM along with the underlying mechanisms, which may offer a promising adjuvant therapy for cancer patients.

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

“…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.…”

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

“…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].…”

The journey of boswellic acids from synthesis to pharmacological activities

“…With a very high incidence and fatality rate, cancer is one of the most lethal diseases that affect humans (Al Serwi et al 2020 ). However, the majority of currently available medications have serious side effects and are frequently unsuccessful as a result of the emergence of chemo-resistance (Kunnumakkara et al 2019 , Halcrow et al 2021 ).…”

“…Multiple cases and fatalities from cancer were attributed to hepatocellular carcinoma (HCC) each year (Vogel et al 2022 ). When the effects of BA were examined, it was discovered that in liver cancer cells, they induced apoptosis and inhibited proliferation via the caspase-8-dependent signaling pathway (Liu et al 2002a , Al Serwi et al 2020 ). Additionally, BA increased levels of caspase-3 activity (Fig.…”