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Airway epithelial damage induced by sulfur mustard in uinea pigs, effects of glucocorticoids

Departments of Physiology, Clinical Pharmacology and Histology, INSERM U296, Faculté de Médecine de Créteil, 94010 Créteil, Centre d'Etudes du Bouchet (Defense Medical Research Center), 91710 Vert Le Petit, France

A. Coste

Departments of Physiology, Clinical Pharmacology and Histology, INSERM U296, Faculté de Médecine de Créteil, 94010 Créteil, Centre d'Etudes du Bouchet (Defense Medical Research Center), 91710 Vert Le Petit, France

M. Levame

Departments of Physiology, Clinical Pharmacology and Histology, INSERM U296, Faculté de Médecine de Créteil, 94010 Créteil, Centre d'Etudes du Bouchet (Defense Medical Research Center), 91710 Vert Le Petit, France

A. Harf

Departments of Physiology, Clinical Pharmacology and Histology, INSERM U296, Faculté de Médecine de Créteil, 94010 Créteil, Centre d'Etudes du Bouchet (Defense Medical Research Center), 91710 Vert Le Petit, France

I. Macquin-Mavier

Departments of Physiology, Clinical Pharmacology and Histology, INSERM U296, Faculté de Médecine de Créteil, 94010 Créteil, Centre d'Etudes du Bouchet (Defense Medical Research Center), 91710 Vert Le Petit, France

E. Escudier

Departments of Physiology, Clinical Pharmacology and Histology, INSERM U296, Faculté de Médecine de Créteil, 94010 Créteil, Centre d'Etudes du Bouchet (Defense Medical Research Center), 91710 Vert Le Petit, France

Sulfur mustard (SM) represents a potential chemical warfare agent. In order to characterize SM-induced airway epithelial damage, we studied the effects of an intratracheal injection of 0.3 mg/kg of SM in guinea pigs, 5 h, 24 h, 14 days and 35 days after exposure. During the acute period, lesions prevailed in tracheal epithelium exhibiting intra-epithelial blisters, inflammatory cell infiltration and columnar cell shedding with exposure of basal cells. Fourteen days after intoxication, tracheal epithelium appeared disorganized and showed a signifi cant decrease in height and cell density. Tracheal epithelium recovery was still not complete even 35 days after SM-intoxication. At day 14, in SM-intoxicated guinea pigs treated with betamethasone from day 7 to day 14, epithelium height, cell density and cell proliferation (evaluated by immunohistochemistry) were significantly increased compared to untreated guinea pigs. In conclu sion, the lesions observed in SM-intoxicated guinea pigs seem to be in accordance with clinical human observa tions and are relevant to the study of airway epithelial damage induced by SM. This animal model could be used to illustrate tracheal epithelium regeneration mainly derived from basal cells and to show glucocorticoid effects on airway epithelial recovery after chemical aggression.

Key Words: epithelial regeneration • glucocorticoids • PCNA

Human & Experimental Toxicology, Vol. 15, No. 12, 964-971 (1996)
DOI: 10.1177/096032719601501204


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