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Efficacy of Geranylgeranylacetone for heat stroke recovery in Fischer 344 rats
Author(s) -
Quinn Carrie M,
Helwig Bryan G.,
Leon Lisa R.,
Ward Jermaine A,
Duran Rocio M.
Publication year - 2013
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.27.1_supplement.1201.5
Subject(s) - hsp70 , albumin , heat shock protein , inducer , medicine , liver function , shock (circulatory) , hsp90 , endocrinology , gene expression , chemistry , pharmacology , gene , biochemistry
Heat Shock Protein 70 (HSP70) functions as a molecular chaperone to prevent the misfolding and aggregation of proteins under stressful conditions. Geranylgeranylacetone (GGA) is a pharmacologic inducer of HSP70 in the absence of heat stress, making GGA a potential candidate for post‐heat injury/stroke (HI/S) therapy. We hypothesized that GGA administered 24h post‐HI/S would augment liver HSP70 gene expression and accelerate HI/S recovery in rats. Male F344 rats (277.5 ± 5.3 g) were orally administered GGA (200 mg/kg bw; n=9) or vehicle (Veh; 1mL; n=9) 24h post‐HI/S (Tc,Max, 41.8°C; radiotelemetry). GGA had no effect on thermal load accrued during heat exposure. Liver HSP70 gene expression (qPCR) and biomarkers of liver function (VetScan; ALT, albumin, bile acids, BUN) were examined at 2 and 10d of recovery. Liver HSP70 gene expression was increased ~2000‐fold through 10d of recovery; GGA had no effect on this response. Bile acids, ALT and BUN were similar between HI/S and non‐heated controls on 2 and 10d regardless of treatment. Conversely, HI/S rats treated with GGA showed significantly lower albumin levels compared to non‐heated controls at 2d (4.24±0.07 v 4.78±0.03 U/L, respectively; ANOVA, p<0.01). Our results suggest that GGA administration 24h post‐HI/S is not an efficacious treatment in rats and may delay recovery of liver function. Research supported by MRMC. Author views not official US Army or DoD policy.