In the 94th Annual Meeting of the Japanese Pharmacological Society, we reported two kinds of pulmonary inflammatory models using lipopolysaccharide (LPS), LPS inhalation model and -GalCer-LPS instillation model. In the previous report, we concluded that these LPS-induced ARI models could be useful to evaluate therapeutic efficacy of drugs used for treatment of pneumonia.In the present study we carried out further research on LPS instillation model with a pretreatment of α-garactosyl ceramid (α-GalCer), and we also examined the effect of exosome from human adipose cell. We evaluated inflammatory cell infiltration in BALF (Broncho Alveolar Lavage Fluid), BALF supernatant cytokine level and SpO2. Exosome was found to be slightly effective to improve symptomatic parameters in this model. The action of exosome changed along with the time of administration. Exosome administrated 4hr after LPS instillation decreased body weight loss, inflammatory cell infiltration, IL-6 and IL-10 levels. On the other hand, administration of exosome 24hr after LPS instillation showed advanced histopathological appearance image of the lung. The results indicate that characteristic pathophysiological change of this model was identified.
Pain of the joint in the osteoarthritis (OA) and neuropathic pain cause a significant decrease in the quality of life (QOL) of the patients. To develop analgesics, a simplified method for evaluating analgesic effect has been becoming necessary although the methods like use of von frey filament, thermal stimulation or a load difference measurement method are existed, which require expert techniques for measurement. Therefore, we tried to use Catwalk which can acquire data by the animal walks to establish a method for pain evaluation in neuropathic pain and MIA-induced OA model in this study. As the results obtained by measuring the pain parameters using the Catwalk, filament method, thermal stimulation method or load difference measurement method, a significant low value was observed in the pain parameters in both the neuropathic pain and OA model animals compared with the normal animals. On the other hand, administration of celecoxib, tramadol and pregabalin showed a significant high value in the pain parameters in the pain model animals compared with the control animals. Based on the above results, it is suggested that walking analysis by Catwalk is useful for evaluation of analgesics.
Pneumonia is recognized to be a more serious disease by the spreads such as recent COVID-19 infectious diseases. It is thought that treatment for the acute pneumonia in particular is important in pneumonia. In generally, LPS-induced ARI animal model are used for the study. Therefore, we made two kinds of pulmonary inflammatory models using the LPS and evaluated and compared them. One is a model to let LPS expose to a whole body, and another one is instillation of LPS to nasal cavity under anesthesia with a pretreatment of α-garactosyl ceramid (αGalCer). These two animal model was evaluated inflammation cells infiltration into lung by BALF and cytokines in BALF supernatant by FCM. And evaluation by drug was carried out oral administration of dexamethasone. As a result, it was revealed that two models were different in a characteristic each. Based upon these results, we confirmed that these two ARI model induced by LPS was the model which could carry out the evaluation of the test article in consideration of a characteristic each. At the commencement of this study, the study protocol was reviewed by the Institutional Animal Care and Use Committee of the test facility and approved by the general manager of the Nonclinical Research Center according to the following guideline: Guidelines for Animal Studies (Nonclinical Research Center, LSI Medience Corporation).
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