NDLI: Protective actions of des-aspartate-angiotensin I in mice model of CEES-induced lung intoxication.

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Protective actions of des-aspartate-angiotensin I in mice model of CEES-induced lung intoxication.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Ng, Eugene Teck-Leong Sim, Meng-Kwoon Loke, Weng-Keong
Description	Author Affiliation: Ng ET ( Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Block MD 11, 10 Medical Drive, Singapore 117597.)
Abstract	The present study investigated the protective actions of des-aspartate-angiotensin I (DAA-I) in mice that were intranasally administered 2-chloroethyl ethyl sulfide (CEES), a half sulfur mustard. The protection was dose-dependent, and an oral dose of 75 mg kgâ »¹ per day administered 18 h post exposure and for the following 13 days, offered maximum protection that increased survival by a third. DAA-I attenuated the early processes of inflammation seen in the CEES-inoculated mice. DAA-I attenuated (i) elevated pulmonary ROS, and gp91-phox protein of NADPH oxidase, a non phagocytic enzyme that generates superoxide and subsequent ROS; (ii) intercellular adhesion molecule-1 (ICAMâ »¹) that is involved in the extravasation of circulating leucocytes; and (iii) myeloperoxidase activity, which is a surrogate enzymatic measurement of neutrophil infiltration. These actions led to improved histological lung structures, and survival of type-1 pneumocytes. The action of DAA-I on animal survival was blocked by losartan, a selective angiotensin AT1 receptor blocker, indicting that the AT1 receptor mediates the protection. The presence of elevated PGE2 and PGI2 in lung supernatants of DAA-I treated CEES-inoculated mice indicates that the two prostaglandins are involved in signaling the protective actions of DAA-I. This finding complements earlier studies showing that DAA-I acts on an indomethacin-sensitive angiotensin AT1 receptor. The findings of the present study are the first demonstration of an angiotensin peptide as an effective antidote for CEES intoxication. DAA-I is also an effective therapeutic intervention against CEES that was instituted at 18 h post exposure, and challenges conventional assumptions of limited efficacy with delayed action against alkylating agents.
File Format	HTM / HTML
ISSN	0260437X
Issue Number	6
Volume Number	31
e-ISSN	10991263
Journal	Journal of Applied Toxicology
Language	English
Publisher	Wiley
Publisher Date	2011-08-01
Publisher Place	Great Britain (UK)
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Toxicology Angiotensin I Analogs & Derivatives Lung Drug Effects Pathology Mustard Gas Pharmacology Animals Bronchoalveolar Lavage Fluid Chemistry Dinoprostone Metabolism Disease Models, Animal Dose-response Relationship, Drug Epoprostenol Intercellular Adhesion Molecule-1 Losartan Male Mice Mice, Inbred Balb C Toxicity Nadph Oxidase Peroxidase Reactive Oxygen Species Receptors, Immunologic Signal Transduction Journal Article
Content Type	Text
Resource Type	Article
Subject	Toxicology

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