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Pyruvate attenuates myoglobin in vitro toxicity.

Monica A Valentovic1, Jennifer Minigh

  • 1Department of Pharmacology, Marshall University School of Medicine, 1542 Spring Valley Drive, Huntington, West Virginia 25704-9388, USA. alentov@marshall.edu

Toxicological Sciences : an Official Journal of the Society of Toxicology
|May 30, 2003
PubMed
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Pyruvate protects against myoglobin-induced kidney damage by reducing oxidative stress and providing energy. This study shows pyruvate significantly lowered markers of renal toxicity in vitro.

Area of Science:

  • Biochemistry
  • Nephrology
  • Toxicology

Background:

  • Myoglobinuria, a complication of crush injury and substance abuse, can lead to acute kidney injury.
  • The direct renal toxicity of myoglobin and potential protective agents require further investigation.

Purpose of the Study:

  • To investigate the in vitro effect of pyruvate on myoglobin-induced renal toxicity.
  • To determine if pyruvate can mitigate cellular damage and energy depletion caused by myoglobin.

Main Methods:

  • Renal slices from Fischer-344 rats were incubated with varying concentrations of myoglobin (0-12 mg/ml).
  • Coincubation with pyruvate (10 mM) was performed for different durations (30 min or 120 min).
  • Measurements included lactate dehydrogenase (LDH) release, adenosine triphosphate (ATP) levels, lipid peroxidation, and glutathione status.

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Main Results:

  • Myoglobin exposure increased LDH release and decreased ATP levels, indicating cellular damage and energy depletion.
  • Coincubation with pyruvate for 120 minutes significantly reduced LDH leakage and maintained higher ATP levels compared to myoglobin alone.
  • Pyruvate prevented myoglobin-induced oxidative stress, as evidenced by reduced lipid peroxidation and preserved glutathione levels.

Conclusions:

  • Pyruvate effectively reduces in vitro renal toxicity induced by myoglobin.
  • Pyruvate's protective mechanisms involve preventing oxidative stress and supplying an energy substrate.
  • These findings suggest pyruvate as a potential therapeutic agent for myoglobinuric acute kidney injury.