PROTECTIVE EFFECT OF U74500A ON PHORBOL MYRISTATE ACETATE–INDUCED ACUTE LUNG INJURY

Authors: Shi-Jye Chu1; Deh-Ming Chang2; David Wang3; Hen-I Lin4; Shih-Hua Lin2; Kang Hsu2

Source: Clinical and Experimental Pharmacology and Physiology, Volume 31, Number 8, August 2004 , pp. 523-529(7)

Publisher: Blackwell Publishing

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Abstract:

SUMMARY

1. The present study was designed to determine whether U74500A could ameliorate acute lung injury (ALI) induced by phorbol myristate acetate (PMA) in our rat isolated lung model compared with any amelioration induced by dimethylthiourea (DMTU), superoxide dismutase (SOD) and catalase.

2. Acute lung injury was induced successfully by PMA during 60 min of observation. At 2 µg/kg, PMA elicited a significant increase in microvascular permeability (measured using the capillary filtration coefficient Kfc), lung weight gain, the lung weight/bodyweight ratio, pulmonary arterial pressure and protein concentration of the bronchoalveolar lavage fluid.

3. Pretreatment with 1.5 mg/kg U74500A significantly attenuated ALI; there was no significant increase in any parameters measured, except for pulmonary arterial pressure. The protective effect of U74500A was approximately the same as that of 600 mg/kg DMTU. However, 6000 U/kg SOD, 50 000 U/kg catalase and 6000 U/kg SOD + 50 000 U/kg catalase had no protective effect.

4. These experimental data suggest that U74500A significantly ameliorates ALI induced by PMA in rats.

Keywords: acute lung injury; catalase; dimethylthiourea; phorbol myristate acetate; superoxide dismutase; U74500A

Document Type: Research article

DOI: 10.1111/j.1440-1681.2004.04043.x

Affiliations: 1: Emergency Medicine and 2: Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, 3: Department of Medicine, Fu-Jen Medical School, Fu-Jen Catholic University and 4: Department of Internal Medicine, Catholic Cardinal Tien Hospital, Fu-Jen Catholic University, Taipei Hsien,Taiwan

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