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Fluconazole attenuates lung injury and mortality in a rat peritonitis model

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Abstract

Objective

Acute lung injury following peritonitis constitutes an enigmatic clinical problem with no specific therapy. Recently, immunomodulators such as azole compounds have been shown to attenuate shock-related tissue injury. The present investigation was undertaken to study the effect of fluconazole on acute lung injury and survival following faecal peritonitis in rats.

Subjects

Male Wistar rats weighing 225–235 g.

Design and setting

Faecal peritonitis (Fp) was produced in four groups of adult male Wistar rats by intraperitoneal administration of non-sterile faecal suspension (1:1 w/v saline). A fifth group of rats was given sterile faecal material (SFM), which served as control.

Interventions

Rats in Fp groups were given fluconazole in doses of 0 mg/kg, 3 mg/kg, 10 mg/kg, and 30 mg/kg by gavage 30 min before induction of peritonitis. The control animals received an equal volume of distilled water.

Measurements and results

Survival over a period of 72 h, oxidative stress, neutrophil activity, and lung injury were measured. This study showed a 90% survival in the fluconazole-treated group compared to only 20% survival in untreated rats (P<0.008 log-rank test). The lungs of animals with Fp showed massive pathological changes including intraalveolar oedema, fibrosis, and mixed inflammatory cell infiltrate. These changes were dose-dependently attenuated by fluconazole. Enhanced oxidative stress (P<0.001) and neutrophil activity in the peritoneal fluid and lung (P<0.001) in Fp animals was dose-dependently reduced by fluconazole.

Conclusion

This study clearly suggests the role of neutrophils in Fp-induced tissue injury/mortality, which may be dose-dependently, attenuated by fluconazole.

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Acknowledgements

The authors wish to thank Mr. DY Nayagam, Mr. Jesuraja Rajakana, and Mr. Khalid Elfaki for their assistance in experimental work and Ms. Tess Jaime for typing the manuscript.

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Authors and Affiliations

  1. Research Centre, Armed Forces Hospital, P.O. Box 7897 (W-912), 11159, Riyadh, Kingdom of Saudi Arabia

    Mohammad Tariq, Mohammed Arshaduddin, Haseeb Ahmad Khan, David Price Evans & Sydney Jacobs

  2. King Faisal University, Dammam, Kingdom of Saudi Arabia

    Ahmed Al Moutaery

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  1. Mohammad Tariq
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  2. Ahmed Al Moutaery
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  3. Mohammed Arshaduddin
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  4. Haseeb Ahmad Khan
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Correspondence to Mohammad Tariq.

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Tariq, M., Moutaery, A.A., Arshaduddin, M. et al. Fluconazole attenuates lung injury and mortality in a rat peritonitis model. Intensive Care Med 29, 2043–2049 (2003). https://doi.org/10.1007/s00134-003-1960-3

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  • DOI: https://doi.org/10.1007/s00134-003-1960-3

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