Irradiation-Induced Damage to the Salivary Glands: The Role of Redox-Active Iron and Copper

• Published in: Radiation research 1997-04, Vol.147 (4), p.468-476
• Main Authors: Nagler, Rafael, Marmary, Yitzhak, Fox, Philip C., Baum, Bruce J., Har-El, Ronit, Chevion, Mordechai
• Format: Article
• Language: English
• Subjects: Ancitabine - pharmacology; Animals; Biological and medical sciences; Copper; Copper - metabolism; Cytoplasmic Granules - drug effects; Cytoplasmic Granules - radiation effects; Cytoplasmic Granules - ultrastructure; DNA damage; Free radicals; Iron; Iron - metabolism; Irradiation; Male; Medical sciences; Non tumoral diseases; Otorhinolaryngology. Stomatology; Oxidation-Reduction; Parotid gland; Parotid Gland - pathology; Parotid Gland - physiology; Parotid Gland - radiation effects; Pilocarpine - pharmacology; Radiation damage; Radiation Protection; Rats; Rats, Wistar; Saliva; Saliva - radiation effects; Saliva - secretion; Salivary glands; Secretion; Submandibular Gland - pathology; Submandibular Gland - physiology; Submandibular Gland - radiation effects; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology; X-Rays
• ISSN: 0033-7587; 1938-5404
• DOI: 10.2307/3579504

The mechanism of irradiation-induced hypofunction of the salivary glands is a process that is not fully understood. Here we examine the hypothesis that intracellular and redox-active ions of iron and copper, which are associated with the secretion granules, play a catalytic role in the irradiation-induced damage. Rats were subjected to head and neck irradiation (15 Gy X rays) and allowed to recover for 2 months. The function of the parotid and submandibular glands was then determined by pilocarpine-stimulated salivary secretion. A 45% decrease in the function of both glands was obtained when compared to nonirradiated controls. Treatment prior to irradiation (90 min) with cyclocytidine (200 mg/kg) led to a massive degranulation of the parotid gland and yielded nearly complete protection from radiation-induced damage. In contrast, pilocarpine stimulation prior to irradiation led to a marginal degranulation of the parotid gland and yielded only 13% protection. Neither agent caused degranulation of the submandibular gland mucous cells or yielded functional protection of this gland. Treatment with both agents yielded a marked increase in iron, copper and manganese levels in the parotid gland saliva. An analogous marked increase in the redox activity of iron and copper ions was recorded for the parotid saliva stimulated by pilocarpine and cyclocytidine. Pilocarpine-stimulated submandibular gland saliva contained metal levels similar to those of the parotid gland saliva. However, no redox activity and no increase in metal mobilization could be demonstrated in the submandibular gland saliva stimulated by both agents. The correlation between the patterns of gland degranulation, mobilization of redox-active metals and the protection of gland function, for both parotid and submandibular glands, focuses attention on the catalytic roles played by transition metal ions in promoting free radical reactions, which likely participate in the process of injury to the tissue.