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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
Summary
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.
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.