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Absolute Quantification of Plasma MicroRNA Levels in Cynomolgus Monkeys, Using Quantitative Real-time Reverse Transcription PCR
Published on: February 12, 2018
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MicroRNA as biomarkers of mitochondrial toxicity
Bethany R Baumgart1, Katherine L Gray1, Jochen Woicke2
1Department of Toxicology, Drug Safety Evaluation, Bristol-Myers Squibb, 4401 Highway 62 East, Mount Vernon, IN 47620, USA.
Toxicology and Applied Pharmacology
|October 18, 2015
Summary
MicroRNAs (miRNAs) show promise as early biomarkers for mitochondrial toxicity. This study found that specific miRNA expression changes correlated with mitochondrial damage in rats treated with toxins.
Area of Science:
- Biochemistry
- Toxicology
- Molecular Biology
Background:
- Mitochondrial toxicity is often detected late, after irreversible cell damage.
- Early detection of mitochondrial dysfunction is crucial for preventing severe cellular damage like apoptosis or necrosis.
Purpose of the Study:
- To identify sensitive, early biomarkers for mitochondrial toxicity.
- To investigate the impact of mitochondrial complex inhibitors on mitochondrial DNA (mtDNA) and microRNA (miRNA) expression.
Main Methods:
- Male Sprague-Dawley rats were administered rotenone (complex I inhibitor) or 3-nitropropionic acid (3-NP, complex II inhibitor) daily for one week.
- Kidney, skeletal muscle, and serum samples were analyzed for mtDNA copy number and miRNA expression.
- Changes in miRNA expression were compared to known mitochondrial functions and damage pathways.
Main Results:
- Significant decreases in mtDNA copy number were observed in skeletal muscle and kidney following rotenone and 3-NP administration.
- Both rotenone and 3-NP altered miRNA expression patterns.
- Observed miRNA changes mirrored those associated with mitochondrial damage, biogenesis, ATP synthesis disruption, and mtDNA depletion.
Conclusions:
- miRNAs may serve as sensitive biomarkers for the early detection of mitochondrial toxicity.
- miRNA profiling offers a potential strategy for monitoring mitochondrial health and identifying toxic insults at an early stage.

