Single Injection of a Sustained-release Prostacyclin Analog Improves Pulmonary Hypertension in Rats

Obata, Hiroaki; Sakai, Yoshiki; Ohnishi, Shunsuke; Takeshita, Satoshi; Mori, Hiromu; Kodama, Makoto; Kangawa, Kenji; Aizawa, Yoshifusa; Nagaya, Noritoshi

doi:10.1164/rccm.200703-349oc

Cited by 42 publications

(32 citation statements)

References 37 publications

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“…In vitro drug release study, drug release from ONO-1301 PLGA MS was sustained release for 3 weeks. A previous study reported the maximum ONO-1301 plasma concentration after oral administration of 30 mg/kg ONO-1301 powder was about 5000 ng/mL in rats, oral administration of 30 mg/kg and 100 mg/kg ONO-1301 powder induced hypotensive action in rats when the plasma concentration of ONO-1301 is beyond 5000 ng/mL (Obata et al, 2008). In this study, the maximum ONO-1301 plasma concentration at 3 h after administration of 10 mg/kg ONO-1301 PLGA MS was 289 ng/mL, which burst release of ONO-1301 is significantly lower than 5000 ng/mL.…”

Section: Discussionmentioning

confidence: 97%

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The effect of treatment with a sustained-release prostacyclin analogue (ONO-1301-loaded PLGA microsphere) on short-term memory impairment in rats with transient global cerebral ischemia

Hazekawa

Sakai

Yoshida

et al. 2012

Journal of Microencapsulation

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The purpose of this study was to prepare the ONO-1301 loaded poly(lactide-co-glycolide) microsphere (ONO-1301 PLGA MS) and to evaluate neuroprotective effects for short-term memory by a single subcutaneous injection of ONO-1301 PLGA MS on repeated induction of cerebral ischemia (2 × 10-min with a 1-min interval) in rat. Drug release profiles from ONO-1301 PLGA MS in vitro and in vivo were evaluated. The extent of ischemic injury was assessed behaviourally using the passive avoidance test and histopathologically by evaluating hippocampal CA1 pyramidal damage on day 42 after ischemia. Experiments in vitro showed that the release of ONO-1301 from ONO-1301 PLGA MS was sustained for approximately 3 weeks with maintenance of steady plasma levels. The neuroprotective effect was shown by treatment with ONO-1301 PLGA MS from 2 days after induction of ischemia behaviourally and histopathologically. These results suggest that ONO-1301 PLGA MS can limit short-term learning injury following global cerebral ischemia.

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Section: Discussionmentioning

confidence: 97%

“…The concentration of ONO-1301 in this solution was analysed by high-performance liquid chromatography (HPLC). The EE was calculated as follows (Obata et al, 2008):…”

Section: Encapsulation Efficiencymentioning

confidence: 99%

The effect of treatment with a sustained-release prostacyclin analogue (ONO-1301-loaded PLGA microsphere) on short-term memory impairment in rats with transient global cerebral ischemia

Hazekawa

Sakai

Yoshida

et al. 2012

Journal of Microencapsulation

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“…Other papers also demonstrated that ONO-1301MS was not only effective but also safe in various animal models. 12,21,22) At this point, we have some unpublished data from human and monkey experiments. These preliminary results suggest that ONO-1301MS can be clinically used without severe systemic adverse effects.…”

Section: Discussionmentioning

confidence: 99%

A Prostacycline Analog Prevents Chronic Myocardial Remodeling in Murine Cardiac Allografts

et al. 2012

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SummaryONO-1301MS is a compound that acts as a prostacyclin agonist with thromboxane A2 synthase inhibitory activity. We investigated the effect of ONO-1301MS on myocardial remodeling in murine cardiac allografts. The hearts of Balb/c mice were transplanted into C3H/He mice (a full allomismatch combination) to assess acute rejection or C57BL/6 hearts into B6.C-H2 KhEg (a class II mismatch combination) to examine chronic rejection. ONO-1301MS did not prolong full allomismatch cardiac graft survival. Severe myocardial fibrosis with high collagen concentration was observed in untreated class II mismatch allografts on day 60. However, significantly suppressed myocardial fibrosis with less collagen synthesis was observed in the ONO-1301MS-treated group compared to the control group. ONO-1301MS could be an effective strategy to suppress chronic myocardial remodeling in cardiac transplantation. (Int Heart J 2012; 53: 64-67)

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“…PGI 2 plays a key role in limiting Th2-mediated airway inflammation (Jaffar, Wan, & Roberts, 2002) and pretreatment with PGI 2 results in considerably attenuated pulmonary inflammation and airway hyperreactivity in mice in response to ovalbumin inhalation (Jaffar, Ferrini, Buford, Fitzgerald, & Roberts, 2007). A novel sustained-release prostacyclin analog, ONO-1301MS, attenuates monocrotaline-induced pulmonary hypertension in rats (Obata et al, 2008) and its action is associated with a marked reduction of TXA 2 (Murakami et al, 2006). The repeated administration of ONO-1301 can attenuate the development of bleomycin-induced pulmonary fibrosis and improve survival in bleomycin mice by inhibiting TXA 2 synthesis (Murakami et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

The effects of vitamin A supplementation on the production of hypersensitive inflammatory mediators of ammonia-induced airways of pigs

Chaung

Hsia

Liu

2008

Food and Agricultural Immunology

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Ammonia utilised for various purposes in the field of agriculture is considered one of the most hazardous pollutants, and is known to irritate the airways of farmers and animals. Vitamin A may participate in the modulation of host immune and inflammatory responses. In this study, the beneficial effects of vitamin A supplementation on ammonia-induced pulmonary inflammation and also lung stress due to suboptimal environmental temperature were examined. The results showed that ammonia inhalation significantly increased thromboxane A 2 (TXA 2 ) and leukotriene C 4 (LTC 4 ) production by the lungs, while vitamin A supplementation significantly reduced the production of TXA 2 and LTC 4 and it also enhanced prostaglandin I 2 (PGI 2 ) in ammonia-induced inflammatory lungs and increased PGI 2 production in the lungs of pigs raised at suboptimal environmental temperature. Thus, exposure to ammonia produces a disruptive defect in the lungs and vitamin A supplementation may relieve this detriment by modulating the production of pulmonary inflammatory mediators.

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Single Injection of a Sustained-release Prostacyclin Analog Improves Pulmonary Hypertension in Rats

Cited by 42 publications

References 37 publications

The effect of treatment with a sustained-release prostacyclin analogue (ONO-1301-loaded PLGA microsphere) on short-term memory impairment in rats with transient global cerebral ischemia

The effect of treatment with a sustained-release prostacyclin analogue (ONO-1301-loaded PLGA microsphere) on short-term memory impairment in rats with transient global cerebral ischemia

A Prostacycline Analog Prevents Chronic Myocardial Remodeling in Murine Cardiac Allografts

The effects of vitamin A supplementation on the production of hypersensitive inflammatory mediators of ammonia-induced airways of pigs

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