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A Comparative Study on the Protection Profile of Lidocaine, Amifostine, and Pilocarpin on the Parotid Gland during Radiotherapy

Departments of ¹ Maxillofacial Surgery and ² Radiotherapy and Nuclear Medicine, University Hospital Schleswig-Holstein; ³ Institute of Anatomy, University of Luebeck, Luebeck, Germany; and ⁴ Institute of Pathology, Helios Medical Centre, Erfurt, Germany

Requests for reprints: Samer G. Hakim, Department of Maxillofacial Surgery, University Hospital Schleswig-Holstein, Campus Luebeck, Ratzeburger Allee 160, 23538 Luebeck, Germany. Phone: 49-451-500-2266; Fax: 49-451-500-4188; E-mail: samer.hakim{at}mkg-chir.mu-luebeck.de.

The aim of this study was to evaluate the individual and the synergetic radioprotective effect of lidocaine, amifostine, and pilocarpin on the parotid gland. Forty-nine rabbits were randomized into seven groups (n = 7)—control, irradiated sham-treated, irradiated/lidocaine–pretreated, irradiated/amifostine–pretreated, irradiated/pilocarpin–pretreated, irradiated/lidocaine + pilocarpin–pretreated, and irradiated/amifostine + pilocarpin–pretreated groups. One week before irradiation (15 Gy) and 72 hours as well as 1 month afterward, the parotid gland was investigated morphologically, sialoscintigraphically, and immunohistochemically with the use of tenascin-C and smooth muscle actin. Compared with control animals, there was a significant reduction of the salivary ejection fraction in the irradiated untreated group 72 hours following radiation. Only animals pretreated with lidocaine or amifostine (alone or combined with pilocarpin) showed a slight nonsignificant reduction of salivary ejection fraction. Immunohistochemically, we observed a significant loss of smooth muscle actin and an up-regulation of tenascin-C expression in irradiated/untreated glands. These changes were less evident in animals pretreated with lidocaine or lidocaine + pilocarpin. Amifostine and pilocarpin did not show any influence on tenascin-C or smooth muscle actin expression. Ultrastructural damage was observed in irradiated untreated and pilocarpin–pretreated glands. In contrast, lidocaine and amifostine could largely preserve the glandular ultrastructure. One month postradiation, all changes were regressive regardless of treatment protocol. Potential radioprotective agents show different effects on both morphology and function of the parotid gland. Associated immunohistochemical and ultrastructural findings could prove the prevailed protection profile of lidocaine. This may provide a prophylactic approach in the field of radioprotection of salivary glands.