Primaquine-induced differential gene expression analysis in mice liver using DNA microarrays.
Primaquine (PQ), a clinically important derivative of 8-aminoquinoline used against the hepatic stages (hypnozoites) of Plasmodium vivax and Plasmodium ovale, was studied to evaluate and compare between mRNA expression, and biochemical and histological parameters of hepatic stress in adult Swiss mice (Mus musculus). Following single oral dose of PQ (40 mg/kg, bw), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) along with hematoxylin and eosin stained liver sections did not show any signs of hepatic stress at 6, 12 and 24 h except for ALT activity at 6h. However, analysis at RNA transcript level revealed consistent and significant deregulation (p<0.01 and two-fold) of 16 probes corresponding to important cellular processes such as protein transportation, transcription regulation, intracellular signaling, protein synthesis, hematopoiesis, cell adhesion and cell proliferation. Pathway analysis identified large number of affected genes corresponding to 40 Gene Ontology terms having a z score greater than 2. These results indicate that PQ at high doses may affect gene expression in liver and may produce undesirable outcomes if consumed for longer durations.
Division of Toxicology, Central Drug Research Institute, M G Marg, Lucknow, India. sanjeevnoel@gmail.com
Sanjeev
S
Noel
Sharad
S
Sharma
Rishi
R
Shanker
Srikanta Kumar
SK
Rath
D000284:Administration, Oral; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D021461:Animals, Outbred Strains; D000962:Antimalarials / Q000633:toxicity*; D001219:Aspartate Aminotransferases / Q000097:blood; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D011319:Primaquine / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D043922:Toxicogenetics / Q000379:methods*
D000962:Antimalarials; D012333:RNA, Messenger; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D011319:Primaquine