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Indomethacin increases organ damage and heat stroke mortality in mice (1104.13)
Author(s) -
Leon Lisa,
Dineen Shauna,
Plamper Mark
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1104.13
Subject(s) - kidney , medicine , biomarker , endocrinology , acute kidney injury , stroke (engine) , liver injury , pharmacology , chemistry , mechanical engineering , biochemistry , engineering
The effect of non‐steroidal anti‐inflammatory drugs (NSAIDs) on the progression of organ damage during heat stroke (HS) recovery is unknown. We examined the effect of oral indomethacin (INDO; 5 mg/kg) on core temperature (T c ; ±0.1°, radiotelemetry), organ (kidney, liver) gene expression of IL‐6 and lipocalin2 (LCN2; an injury biomarker), and survival of male C57BL/6J mice (23.7±0.5g; 6‐9 mice/group) at T c,Max (42.4°C), 3h and 24h of HS recovery. INDO had no effect on T c during heat exposure or recovery. INDO caused ~50% increase in HS mortality, which was associated with increased gut hemorrhaging. In HS survivors, kidney IL‐6 (4‐ to 38‐fold) and LCN2 (6‐ to 9‐fold) expression was increased throughout recovery and INDO potentiated these responses (5‐ to 280‐fold and 20‐ to 56‐fold, respectively; P<0.05). Liver IL‐6 (2‐to 4‐fold) and LCN2 (14‐ to 16‐fold) expression was lower than the kidney, but these responses were also potentiated by INDO (IL‐6: 3‐17‐fold; LCN2: 20‐ to 120‐fold; P<0.05). Plasma LCN2 was increased by INDO in non‐heated control and HS mice at 24h of recovery indicating an effect of the drug alone on organ damage. NSAIDs are known to cause gut bleeding, but these studies suggest there is a heat‐NSAIDs interaction that exacerbates the toxic effects of this drug. Plasma LCN2 may be a sensitive biomarker of organ damage in our model. Author views not official US Army or DoD policy. Grant Funding Source : DoD Medical Research and Materiel Command