PMID- 25070830
OWN - NLM
STAT- MEDLINE
DCOM- 20150402
LR  - 20140729
IS  - 2284-0729 (Electronic)
IS  - 1128-3602 (Linking)
VI  - 18
IP  - 15
DP  - 2014
TI  - The anti-inflammatory effects of 1,1 dimethyl-4-phenylpiperazinium (DMPP) 
      compared to dexamethasone in a guinea pig model of ovalbumin induced asthma.
PG  - 2228-36
LID - 7668 [pii]
AB  - BACKGROUND 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 
      (OVA-sensitized 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 (TNFalpha), 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-alpha, 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-alpha, 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. CONCLUSIONS: 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.
FAU - Murad, H A
AU  - Murad HA
AD  - Department of Pharmacology, Faculty of Medicine, Rabigh, King Abdulaziz 
      University, Jeddah, Saudi Arabia. helmy_amany@yahoo.com.
FAU - Hasanin, A H
AU  - Hasanin AH
LA  - eng
PT  - Journal Article
PL  - Italy
TA  - Eur Rev Med Pharmacol Sci
JT  - European review for medical and pharmacological sciences
JID - 9717360
RN  - 0 (Anti-Asthmatic Agents)
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Interleukin-6)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 54-77-3 (Dimethylphenylpiperazinium Iodide)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - 9006-59-1 (Ovalbumin)
SB  - IM
MH  - Animals
MH  - Anti-Asthmatic Agents/pharmacology
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Asthma/*chemically induced/*drug therapy/metabolism
MH  - Bronchoalveolar Lavage Fluid/chemistry
MH  - Dexamethasone/*pharmacology
MH  - Dimethylphenylpiperazinium Iodide/*pharmacology
MH  - Disease Models, Animal
MH  - Eosinophils/drug effects/metabolism
MH  - Guinea Pigs
MH  - Immunoglobulin E/metabolism
MH  - Interleukin-6/metabolism
MH  - Leukocyte Count/methods
MH  - Lung/drug effects/metabolism
MH  - Lymphocytes/drug effects/metabolism
MH  - Male
MH  - Monocytes/drug effects/metabolism
MH  - Muscle, Smooth/drug effects/metabolism
MH  - Neutrophils/drug effects/metabolism
MH  - Ovalbumin/*adverse effects
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 2014/07/30 06:00
MHDA- 2015/04/04 06:00
CRDT- 2014/07/30 06:00
PHST- 2014/07/30 06:00 [entrez]
PHST- 2014/07/30 06:00 [pubmed]
PHST- 2015/04/04 06:00 [medline]
AID - 7668 [pii]
PST - ppublish
SO  - Eur Rev Med Pharmacol Sci. 2014;18(15):2228-36.