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

Abstract

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 A 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 A 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 A 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. (Cancer Res 2005; 65(22): 10486-93)

Radioprotective Effect of Lidocaine on Neurotransmitter Agonist-Induced Secretion in Irradiated Salivary Glands

“…Prompted by a finding stabilizing the basolateral membrane using prophylactic lidocaine reduced radiation-induced damage in cultured parotid acinar cells [10], we recently verified that lidocaine was able to prevent radiation-induced damage to the function and ultrastructure of salivary glands in vivo in rabbits [1], [11]. However, the pharmacological mechanism of lidocaine's radioprotective profile is still largely unknown.…”

A review of radiation countermeasures focusing on injury-specific medicinals and regulatory approval status: part I. Radiation sub-syndromes, animal models and FDA-approved countermeasures

“…This animal model has been used to study the radiation-induced injuries and investigate radiation countermeasures using different radiation sources. There are several reports for studying amifostine using this animal model (Bohuslavizki et al 1998(Bohuslavizki et al , 1999Hakim et al 2005). Fms (mcdonough feline sarcoma viral oncogene homolog)-related tyrosine kinase-3 ligand (FLT3L) has also been tested for efficacy and compared with G-CSF's therapeutic efficacy either alone or in combination using 60 Co c-irradiated New Zealand White rabbits.…”

Pharmacological prevention of radiation-induced dry eye-an experimental study in a rabbit model

“…Values were expressed as the mean ± SEM. Areas without acinar cells (fatty tissue) were not considered for evaluation [6].…”

“…On the other hand, various pharmacological substances such as pilocarpine, amifostine and recently lidocaine have been used with more or less success in experimental and clinical studies in order to reduce radiation-induced damage to salivary glands and the subsequent xerostomia [6]. The mechanisms of radioprotection by these substances are not yet completely understood.…”