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A Hydrogen Sulfide Donor NSAID Influences Inflammatory Cell Responses Following Exertional Heat Stroke
Author(s) -
Robinson Gerard,
Garcia Christian,
Iwaniec John,
Sheikh Laila,
Murray Kevin,
Berlet Reed,
Laitano Orlando,
Clanton Thomas
Publication year - 2019
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.2019.33.1_supplement.764.4
Subject(s) - medicine , stroke (engine) , inflammation , placebo , diclofenac , immune system , ibuprofen , pharmacology , anesthesia , immunology , pathology , mechanical engineering , alternative medicine , engineering
One of the consequences of exposure to exertional heat stroke (EHS) is marked damage to the GI tract. GI damage is believed to promote EHS‐induced activation of the immune system and to be a major contributor to the morbidity and mortality of EHS. We hypothesized that the use of non‐steroidal anti‐inflammatory drugs (NSAIDS), so commonly used in exercising humans, would amplify this damage, make subjects more susceptible to EHS and result in greater GI damage and inflammation. We also hypothesized that the use of next generation NSAIDs containing a hydrogen sulfide (H 2 S) donor, shown to protect the GI tract, would suppress the damaging effects of unmodified NSAIDs. In this study we focus on the impact of both forms of NSAIDs on immune cell populations in the blood following EHS. To test this, we utilized a preclinical mouse model of EHS in mice, previously developed in our laboratory. METHODS C57BL6/J male mice were implanted with temperature telemetry devices. The mice were exercise trained for 3 weeks prior to undergoing a forced running wheel EHS protocol at 37.5°C. The EHS endpoint was loss of consciousness, occurring at core temperatures of ~42.2°C. During 48 hours prior to the EHS protocol, the animals were given ad libitum access to a chow embedded with analgesic doses Ibuprofen (IBU), Diclofenac (DC), or Diclofenac + H 2 S (HS) (i.e. ATB‐337, Antibe Corp) or placebo (PL). Three hours post‐EHS, the mice were sacrificed and blood was collected for hematological analyses. RESULTS Total white blood cell count was lower in the DC and IBU groups compared to the control group (p=0.0079, p=0.0011 respectively). There was no difference detected between the control and the HS group. Lower monocyte (p=0.0017, p=0.0032) and neutrophil counts (p=0.0076, p= 0.0002) were observed in the DC and IBU groups compared to controls. No differences in monocyte or neutrophil counts were observed between the control and HS groups. EHS decreased mean corpuscular volume (MCV), presumably due to hemoconcentration during heat exposure. Treatment with IBU and DC attenuated this decrease in MCV compared to both PL and HS donor. DISCUSSION The data are consistent with the hypothesis that, following EHS, there is a greater migration of circulating monocytes and neutrophils from the blood into damaged organs such as the GI tract. With the NSAID‐H 2 S donor, this effect was attenuated. Previous studies have shown that IBU and DC directly interact with RBC membranes, altering their morphology such that the RBCs resemble stomatocytes. The H 2 S donor appears to prevent this change. Overall, the H 2 S donor blocks the hematological associated‐effects of traditional NSAIDs on the responses to EHS. These data suggest that the H 2 S donors may prevent some negative impacts of heat related injury created by use of traditional NSAIDs during EHS . Author's Views not official US Army or DoD Policy . Support or Funding Information Supported by the DoD W81XWH‐15‐2‐0038 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .