Radiotherapy-induced salivary dysfunction: Structural changes, pathogenetic mechanisms and therapies

Purpose: This review addressed the structural changes observed in salivary glands and pathogenic mechanisms resulting from oxidative stress caused by radiotherapy. The preventive and regenerative therapies for altered acinar morphology and glandular function were also reviewed. Among acute and late microscopic alterations in glandular tissue, there are particularly changes indicative of cell death, hypovascularization, formation of fibrous tissue and edema. A critical role was identified for the Akt-MDM2-p53 pathway in the suppression of DNA damage-induced apoptosis in acinar cells. Prophylactic treatment with pilocarpine, cevilemine, bethanechol and isoproterenol has shown a positive effect on salivary flow, but lasting results have not been observed. Growth factors, histamine and lidocaine, have also demonstrated radioprotective effects on the salivary glands. Stem cell preservation and transplantation may be an alternative to maintain tissue homeostasis and thus allow glandular regeneration. Conclusion: Knowledge of the structural changes observed in the salivary glands contributes to proving the short- and long-term efficacy of the therapies investigated. It is important to know the mechanisms involved in radiation-induced damage, since the control of the pathogenic mechanisms can inhibit the initial process of tissue degeneration. The challenge for investigators is to protect normal cells selectively, without promoting tumor growth. (C) 2015 Elsevier Ltd. All rights reserved.