Preclinical 28-Day Inhalation Toxicity Assessment of <i>S</i>-Nitrosoglutathione in Beagle Dogs and Wistar Rats
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- Dorothy B. Colagiovanni
- N30 Pharma, LLC, Boulder, CO, USA
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- Daxa Borkhataria
- Corvax Consulting, Herfordshire, UK
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- Doug Looker
- N30 Pharma, LLC, Boulder, CO, USA
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- Detlef Schuler
- Harlan Laboratories, Itingen/Switzerland
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- Corinna Bachmann
- Harlan Laboratories, Itingen/Switzerland
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- Peter Sagelsdorff
- Harlan Laboratories, Itingen/Switzerland
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- Naveed Honarvar
- Harlan Laboratories, Itingen/Switzerland
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- Gary J. Rosenthal
- N30 Pharma, LLC, Boulder, CO, USA
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説明
<jats:p> To support clinical development of S-nitrosoglutathione (GSNO) as a therapeutic agent, 28-day toxicology studies in rats and dogs were conducted. Rats (21-25/sex) and dogs (3-5/sex) were exposed for 4 hours or 1 hour, respectively, to inhaled GSNO (0, 3, 9.3, 19, and 28 mg/kg per d in rats and 0, 4.6, 9.0, and 16.2 mg/kg per d in dogs) or vehicle daily via a nebulizer. Animals were monitored throughout the 28-day dosing period and during a postexposure recovery period. Complete necropsy and tissue examinations were performed. Experimental end points included clinical pathology, toxicokinetics, and immunotoxicology. No biologically significant adverse findings were noted in either species, and the no observed adverse effect levels (NOAELs) under these conditions were the highest achieved doses (28 and 16.2 mg/kg per d in rats and dogs, respectively). These data demonstrate that GSNO is well tolerated in rodents and dogs and predict a favorable toxicity profile in humans, thus supporting future clinical development of GSNO or closely related compounds. </jats:p>
収録刊行物
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- International Journal of Toxicology
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International Journal of Toxicology 30 (5), 466-477, 2011-08-25
SAGE Publications