NO, way to go: critical amino acids to replenish nitric oxide production in treating mucositis

Abstract

Purpose of review There is still an unmet need for preventive and treatment strategies for chemotherapy-induced and radiotherapy-induced mucositis and its associated systemic inflammatory response (SIR) in cancer patients. Because of citrulline depletion due to cytotoxic therapy, nitric oxide (NO) production can be reduced, limiting its effect in many physiological processes. Restoring NO production could relieve mucositis severity by supporting host damage control mechanisms. Amino acids glutamine, arginine and citrulline are involved in NO production. This review including recent literature of preclinical and clinical studies will discuss the potential benefits of glutamine, arginine and citrulline on mucositis development with focus on NO production. Recent findings Mucositis severity is more defined by host response to DNA damage than by DMA damage itself. Citrulline depletion because of afunctional enterocytes could be responsible for NO depletion during cytotoxic therapy. Restoring NO production during cytotoxic therapy could have a beneficial effect on mucositis development. Citrulline seems a more promising NO donor than glutamine or arginine during cytotoxic therapy, although clinical studies in mucositis patients are currently lacking. Summary Glutamine, arginine and citrulline show in-vitro beneficial effects on inflammatory processes involved in mucositis. Translation to the clinic is difficult as demonstrated with use of glutamine and arginine. Citrulline, being the most potent NO donor with excellent oral bio-availability, is very promising as treatment choice for mucositis and its use deserves to be investigated in clinical trials with mucositis patients.