Alteration of the Redox State with Reactive Oxygen Species for 5-Fluorouracil-Induced Oral Mucositis in Hamsters

Abstract

Oral mucositis is often induced in patients receiving cancer chemotherapy treatment. It has been reported that oral mucositis can reduce quality of life, as well as increasing the incidence of mortality. The participation of reactive oxygen species (ROS) in the pathogenesis of oral mucositis is well known, but no report has actually demonstrated the presence of ROS. Thus, the purpose of this study was thus to demonstrate the involvement of ROS and the alteration of the redox state in oral mucositis using an in vivo L-band electron spin resonance (ESR) technique. An oral mucositis animal model induced by treatment of 5-fluorouracil with 10% acetic acid in hamster cheek pouch was used. Lipid peroxidation was measured as the level of malondialdehyde determined by the thiobarbituric acid reaction. The rate constants of the signal decay of nitroxyl compounds using in vivo L-band ESR were calculated from the signal decay curves. Firstly, we established the oral mucositis animal model induced by treatment of 5-fluorouracil with acetic acid in hamster cheek pouch. An increased level of lipid peroxidation in oral mucositis was found by measuring malondialdehyde using isolated hamster cheek pouch ulcer. In addition, as a result of in vivo L-band ESR measurements using our model animals, the decay rate constants of carbamoyl-PROXYL, which is a reagent for detecting the redox balance in tissue, were decreased. These results suggest that a redox imbalance might occur by excessive generation of ROS at an early stage of oral mucositis and the consumption of large quantities of antioxidants including glutathione in the locality of oral mucositis. These findings support the presence of ROS involved in the pathogenesis of oral mucositis with anti-cancer therapy, and is useful for the development of novel therapies drugs for oral mucositis.

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

“…The current study confirmed that administration of 5-FU induced a significant oxidative stress in oral mucosal tissue through enhancing lipid peroxidation, accompanied with a notable depletion of GSH. These results are consistent with previous studies which affirmed the induction of potential oxidative stress followed by 5-FU injection, leading to cell death in oral mucosa (23,31) . Our findings of the reversal of these alterations by concomitant administration of GH are clear evidence of its inherent antioxidant activity.…”

Ketoprofen-loaded Eudragit electrospun nanofibers for the treatment of oral mucositis

“…22 To induce mucosal ulcer, 50% acetic acid-soaked cotton bud was pressed on the buccal mucosal tissue of the anesthetized rabbits for 60 seconds on both sides of the buccal cavity. [23][24][25] After induction of mucositis, rabbits were divided into two groups containing three in each group. Rabbits in group 1 were treated by the selected formula of 20% EL-NF loaded with 20% KET (F1), while group 2 served as oral mucositis control (nontreated group).…”

Taurine ameliorates 5-flourouracil-induced intestinal mucositis, hepatorenal and reproductive organ damage in Wistar rats

“…6,7 Overproduction of reactive oxygen species (ROS) and inflammatory mediators by chemotherapeutic drugs causes damage or modification of cellular macromolecules resulting in up or down expression of regulators of normal cellular physiology. 8,9 Chemotherapeutic treatment of 5-FU is associated with severe toxic effects and varies dose dependently with patient to patient and sometimes leads to discontinuation of chemotherapy. 5-FU targets specifically not only cancer or tumor cells but also normal proliferating cells causing inhibition of normal cell proliferation, genomic instability, overproduction of different reactive toxic moieties or mediators, and necrosis leading to severe toxic effects and complications.…”