The anti-inflammatory effects of 1,1 dimethyl-4-phenylpiperazinium (DMPP) compared to dexamethasone in a guinea pig model of ovalbumin induced asthma

Abstract

BACKGROUD AND AIM: Inflammatory cells involved in the pathophysiology of asthma express nicotinic receptor. Therefore 1,1 dimethyl(-4-)phenylpiperazinium (DMPP) in two doses were compared to dexamethasone in asthmatic guinea pigs. MATERIALS AND METHODS: Six groups were included; Normal control and five asthmatic (OVAsensitized and challenged) groups; which were treated for 10 days as follows: two vehicles, dexamethasone (DEXA, 1 mg/kg) and DMPP (0.4 and 0.8 mg/kg) groups. Pulmonary functions and airway hyper-responsiveness were assessed. Leukocytic count, tumor necrosis factor-alpha (TNFa), interleukin-6 (IL-6) and immunoglobulin E (IgE) were measured in both blood and bronchoalveolar lavage fluid (BALF). Histopathological examination of the lung tissues was conducted. RESULTS: Asthmatic untreated animals exhibited significant increase in early and late airway resistance (RxV) and airway hyper-responsiveness, with reduction in tidal volume. Both blood and BALF showed significant increase in total leukocytic count (TLC), eosinophils, lymphocytes, monocytes, TNF-a, IL-6 and IgE with significant decrease in neutrophils. Airway inflammatory cell infiltration and smooth muscle thickness significantly increased. DMPP 0.4 mg/kg significantly decreased late phase RXV, TLC, BALF lymphocytes, TNF-a, smooth muscle thickness and increased neutrophils in BALF over both DEXA and DMPP 0.8 mg/kg. Moreover, DMPP 0.4 mg/kg significantly decreased IL-6 and BALF eosinophils than DMPP 0.8 mg/kg and decreased serum IgE and parenchymal inflammatory infiltration than DEXA. CONCLUNSIONS: Low dose DMPP has more anti-inflammatory effect than a high dose in most parameters and sometimes than dexamethasone. Cholinergic anti-inflammatory pathway may therefore represent a potential drug target for allergic asthma. The dose related effect of DMPP and the mechanism underlying this effect require further evaluation.