Abstract
Oxidative stress and cellular injury have been implicated in induction of HSP72 by alcohol. We investigated the association between HSP72 induction and oxidative stress in mouse tissues following short-term administration of high doses of alcohol and caffeine alone or in combination. Adult male C57BL/6J mice were gavaged with vehicle, alcohol (∼1.7 g/kg/day), caffeine (∼44 mg/kg/day), or alcohol plus caffeine once daily for ten consecutive days. Upon completion of the treatments, tissues were collected for structural and biochemical analyses. Alcohol alone caused mild to moderate lesions in heart, liver, and gastrocnemius muscle. Similar structural changes were observed following administration of alcohol and caffeine combined. Alcohol administration also led to decreased glutathione levels in all three tissues and reduced plasma superoxide dismutase capacity. In contrast, alcohol and caffeine in combination reduced glutathione levels only in liver and gastrocnemius muscle and had no effect on plasma superoxide dismutase. Significant elevations in HSP72 protein and mRNA and in HSF1 protein levels were noted only in liver by alcohol alone or in combination with caffeine. No significant changes in morphology and HSP72 were detected in any tissues tested following administration of caffeine alone. These results suggest that a redox mechanism is involved in the structural impairment caused by short-term high-dose alcohol. Oxidative tissue injury by alcohol may not be associated with tissue HSP72 induction. Induction of HSP72 in liver by alcohol is mediated at both the transcriptional and translational levels.
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Acknowledgments
We consulted Dr. Cara Olsen, Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences (USUHS), for statistical analysis. This work was supported by USUHS Grant R091EH and the Office of Naval Research Grant N0001411MP20025.
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Islam, A., Abraham, P., Hapner, C.D. et al. Tissue-specific upregulation of HSP72 in mice following short-term administration of alcohol. Cell Stress and Chaperones 18, 215–222 (2013). https://doi.org/10.1007/s12192-012-0375-x
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DOI: https://doi.org/10.1007/s12192-012-0375-x