GSK2193874 treatment at heatstroke onset reduced cell apoptosis in heatstroke mice

Cell Mol Biol (Noisy-le-grand). 2018 May 30;64(7):36-42.

Abstract

Heatstroke is still a potentially fatal threat during summer heat waves, despite improved prevention and treatment. It is reported that the transient receptor potential vanilloid 4 (TRPV4) inhibitor may protect septicemia mice. Many aspects of heatstroke have been defined, from the sepsis-mimic inflammatory response to hyperthermia. Hence, TRPV4 may be a therapeutic target for heatstroke. The results in murine models of heatstroke verified that GSK2193874, as a selected TRPV4 inhibitor, was injected at heatstroke onset, and then reduced the reduction of core temperature, the death rate, wet/dry ratio of the lung, levels of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6, coagulation indicators, the degree of organ injury, and caspase-3/7 activity (P<0.05). But GSK2193874 treatment before heat stress did not improve the symptoms of heatstroke mice. Therefore, TRPV4 should be involved in heatstroke-induced injury. Timely GSK2193874 administration may be useful to reduce heatstroke-induced injury. TRPV4 may be a potential new therapeutic target in fatal heatstroke.

Keywords: Coagulation indicator.; Core temperature; GSK2193874; Heatstroke; TRPV4.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Caspase 7 / metabolism
  • Disease Models, Animal
  • Heat Stroke / complications
  • Heat Stroke / drug therapy*
  • Heat Stroke / pathology
  • Hot Temperature / adverse effects
  • Interleukin-6 / blood
  • Interleukin-6 / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Piperidines / pharmacology*
  • Piperidines / therapeutic use
  • Pulmonary Edema / drug therapy*
  • Pulmonary Edema / etiology
  • Pulmonary Edema / pathology
  • Quinolines / pharmacology*
  • Quinolines / therapeutic use
  • TRPV Cation Channels / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Anti-Inflammatory Agents
  • GSK2193874
  • Interleukin-6
  • Piperidines
  • Quinolines
  • TRPV Cation Channels
  • Trpv4 protein, mouse
  • Tumor Necrosis Factor-alpha
  • Casp3 protein, mouse
  • Casp7 protein, mouse
  • Caspase 3
  • Caspase 7