Preemptive Pharmacologic Intervention in Radiation-Induced Salivary Dysfunction

Abstract

Xerostomia (“dry mouth”) is a symptom of several diseases. It also occurs as a side effect of certain therapeutic interventions, most frequently pharmacotherapy. The most severe and irreversible forms of salivary dysfunction result from damage to or loss of salivary acinar cells. One of the severest forms of iatrogenic salivary gland destruction results from the therapeutic doses of irradiation given to treat head and neck cancer or to purge the bone marrow before transplantation. Xerostomia encompasses a wide range of involvement, from an inconvenience when mild, to a debilitating condition when severe. Reports of the symptom of dry mouth by patients do not always correlate with the degree of diminished salivary flow. However, a significant loss of stimulated flow makes it difficult to process solid food into a bolus that can be swallowed. If sustained, nutritional deficiencies may result. Saliva also facilitates formation of speech patterns. Its loss hinders speaking and communicating, possibly causing the patient to withdraw from social interaction. Together these conditions can impair the physiological and psychological well-being of the patient Thousands of individuals undergo radiation therapy for head and neck cancer in the United States each year. Increasing numbers are receiving total body radiation before transplantation of bone marrow. Although the salivary gland is not one of the more actively dividing organs in the body, nevertheless it ranks as one of the most radiosensitive. The mechanism of this sensitivity is not understood. This article reviews human and animal pathophysiology of radiation-induced salivary damage. We also discuss animal studies that have employed various strategies to modify and clarify this process. Finally, we describe encouraging results from early clinical trials suggesting that protection of salivary glands during therapeutic irradiation may be possible.

Xerostomia and hypofunction of the salivary glands in cancer therapy

“…Acinar cells surviving irradiation in vitro are functionally similar to nonirradiated cells [32, 120,167]. However, the nerve function seems not to be significantly affected after radiation (for review see [167]). However, the nerve function seems not to be significantly affected after radiation (for review see [167]).…”

“…Most of these studies have been conducted in vari-ous animal models, mostly in rats and monkeys (for review see [119]). The contradictory results of these studies may not only reflect the fact that there are considerable anatomical, morphological, physiological, and biochemical differences between the salivary glands of different species [183], but also rest on differences in experimental design, radiation dose and monitoring technique (for review see [167]). Salivary glands of the rat appear to be more highly radioresistant than human salivary glands [111].…”

Current therapies for xerostomia and salivary gland hypofunction associated with cancer therapies

“…Better fractionation schemes, more accurate focusing techniques using 3-D planning and unilateral irradiation [22] have made it possible to reduce the sideeffects of radiation therapy considerably. Such prophylactic drugs as amifostine [8] or isoproterenol plus pilocarpine [42] may prevent dramatic hypofunction of the salivary glands, and taste problems after irradiation of the head and neck region can be diminished by using zinc sulphate [33]. Pilocarpine, when administered before each session of irradiation, also exerts functional effects against xerostomia [4].…”

Radioprotection of the mice parotid gland by isoproterenol: study on morphometry of secretory granules and on autoradiography

“…cAMP reportedly shows radioprotective effects on rat parotid glands. 43,44 Taylor and Miller 45 proposed several means of protecting the salivary glands from radiation damage: (1) decrease in free radicals, (2) recovery by cell growth, (3) modulation of signal transduction system, and (4) alteration of oxygen level in salivary glands. Additionally, in investigations of the morphological changes, level of salivary secretion, intracellular levels of Na + and K + , and amylase secretion level after X-ray irradiation subsequent to administration of various neurostimulants, 13,46-50 the lethality, sublethality, and recovery of irradiated cells was studied, taking into consideration that (1) the administration of a neurostimulant tends to induce a lethal disorder during the initial stage of postirradiation, (2) damaged cells tend to be excluded from the acinus, and (3) the growth of surviving cells is stimulated and tissue regeneration is likely to be induced.…”