Efficacy of Geranylgeranylacetone for heat stroke recovery in Fischer 344 rats
Abstract
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 01, 2013
- Source ID
- 10.1096/fasebj.27.1_supplement.1201.5
Entities
People
- Bryan G. Helwig
- Carrie M. Quinn
- Jermaine A. Ward
- Lisa R. Leon
- Rocio M. Duran
Organizations
- United States Army Medical Research and Development Command