A comparative study on the protection profile of lidocaine, amifostine, and pilocarpin on the parotid gland during radiotherapy.
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 alpha 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 alpha 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 alpha 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.
Hakim
Samer G
SG
Department of Maxillofacial Surgery, University Hospital Schleswig-Holstein, Luebeck, Germany. samer.hakim@mkg-chir.mu-luebeck.de
Kosmehl
Hartwig
H
Lauer
Isabel
I
Nadrowitz
Roger
R
Wedel
Thilo
T
Sieg
Peter
P
D000199:Actins / Q000378:metabolism; D004999:Amifostine / Q000494:pharmacology*; D000818:Animals; D004357:Drug Synergism; D005260:Female; D008012:Lidocaine / Q000494:pharmacology*; D046529:Microscopy, Electron, Transmission; D010306:Parotid Gland / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects* / Q000648:ultrastructure; D010862:Pilocarpine / Q000494:pharmacology*; D011817:Rabbits; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D019063:Tenascin / Q000378:metabolism
D000199:Actins; D011837:Radiation-Protective Agents; D019063:Tenascin; D010862:Pilocarpine; D008012:Lidocaine; D004999:Amifostine