title: Treatment responses of procaterol and CD38 inhibitors in an ozone-induced airway hyperresponsiveness mice model.
abstract: Airway hyperresponsiveness (AHR) and airway inflammation are key pathophysiological features of many respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD). To evaluate the treatment responses of procaterol and CD38 inhibitors in an ozone-induced AHR mice model, we hypothesized that procaterol and two synthetic CD38 inhibitors (Compounds T and H) might have therapeutic effects on the ozone-induced AHR mice model, and the nuclear factor-kappaB (NF-κB) pathway and the CD38 enzymatic activity might be involved in the mechanisms. With the exception of the Control group, ozone exposure was used to establish an AHR model. Male Kunming mice in the Procaterol and CD38 inhibitors groups were treated with an emulsifier of procaterol hydrochloride, Compound T or H. Results indicated that (1) no drug showed severe toxicity in this study; (2) ozone exposure induced airway inflammation and AHR; (3) intragastric treatment with procaterol and Compound T achieved potent therapeutic effects, but Compound H did not show any therapeutic effect; (4) the NF-κB pathway was involved in both the pathogenic mechanisms of ozone and therapeutic mechanisms of procaterol and Compound T; (5) however, the in vivo effect of Compound T was not caused by its inhibitory activity on CD38. Taken together, procaterol and Compound T are potentially good drugs to treat asthma and COPD complicated with ozone exposure.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, P. R. China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Deng
authors.forename: Zhan-Cheng
authors.initials: ZC
authors.lastname: Gao
authors.forename: Hui-Qi
authors.initials: HQ
authors.lastname: Ge
authors.forename: Liang-Ren
authors.initials: LR
authors.lastname: Zhang
authors.forename: Jun-Jun
authors.initials: JJ
authors.lastname: Zhou
authors.forename: Zhi-Peng
authors.initials: ZP
authors.lastname: Zhu
authors.forename: Dong-Ying
authors.initials: DY
authors.lastname: Wu
authors.forename: Shuang-Yong
authors.initials: SY
authors.lastname: Sun
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Pu
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000037:antagonists & inhibitors; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001565:Benzoates / Q000494:pharmacology / Q000627:therapeutic use*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004195:Disease Models, Animal; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D007958:Leukocyte Count; D008168:Lung / Q000276:immunology / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors; D016210:Methacholine Chloride; D051379:Mice; D016328:NF-kappa B / Q000276:immunology; D010126:Ozone; D017265:Procaterol / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D018927:Anti-Asthmatic Agents; D001565:Benzoates; D007211:Indoles; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D016210:Methacholine Chloride; D010126:Ozone; C498155:Cd38 protein, mouse; D051997:ADP-ribosyl Cyclase 1; D017265:Procaterol