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Primaquine-induced differential gene expression analysis in mice liver using DNA microarrays
Sanjeev Noel1, Sharad Sharma, Rishi Shanker
1Division of Toxicology, Central Drug Research Institute, M G Marg, Lucknow, India. sanjeevnoel@gmail.com
Toxicology
|August 10, 2007
Summary
Primaquine (PQ), an antimalarial drug, did not cause significant liver damage in mice at high doses. However, it altered gene expression related to vital cellular functions, suggesting potential risks with prolonged use.
Area of Science:
- Pharmacology
- Hepatology
- Molecular Biology
Background:
- Primaquine (PQ) is a crucial 8-aminoquinoline antimalarial drug.
- It is effective against the hepatic stages of Plasmodium vivax and Plasmodium ovale.
Purpose of the Study:
- To evaluate and compare mRNA expression, biochemical, and histological markers of hepatic stress.
- To assess the effects of a single high dose of Primaquine in adult Swiss mice.
Main Methods:
- Mice received a single oral dose of Primaquine (40 mg/kg).
- Liver function was assessed via ALT and AST enzyme activity.
- Histological analysis used hematoxylin and eosin staining.
- Gene expression changes were analyzed using RNA transcript levels and pathway analysis.
Main Results:
- Biochemical and histological analyses showed no significant hepatic stress, except for transient ALT elevation at 6 hours.
- RNA transcript analysis revealed significant deregulation (p<0.01, two-fold) in 16 probes related to cellular processes.
- Pathway analysis identified numerous affected genes linked to 40 Gene Ontology terms (z-score > 2).
Conclusions:
- High-dose Primaquine may impact liver gene expression without immediate biochemical or histological signs of stress.
- Prolonged Primaquine consumption could potentially lead to adverse outcomes due to altered gene expression.
