Identification of differentially expressed genes after acute exposure to bulaquine (CDRI 80/53) in mice liver

Sanjeev Noel, Sharad Sharma, Rishi Shankar, Srikanta Kumar Rath

Research output: Contribution to journalArticle

Abstract

Therapeutic agents derived from 8-aminoquinoline possess potent activity against hepatic stages of plasmodia. Bulaquine (CDRI 80/53), an enamine analogue of primaquine and a relatively new derivative of 8-aminioquinoline, synthesized at the Central Drug Research Institute, Lucknow, India, has shown promising activity against hypnozoites of Plasmodium vivax and Plasmodium ovale. Moreover, it has been found to be three to four times safer than primaquine in pre-clinical studies. In this study, global gene profiling using 22,827 probes was carried out in the livers of male Swiss mice to identify affected genes and cellular pathways at 6, 12 and 24 hr after a single oral dose of bulaquine (40 mg/kg). Present gene expression analysis revealed perturbation in 11 probes (P <0.01 and 2-fold), including those corresponding to protein synthesis, cell division, protein ubiquitination, transcription regulation and steroid biosynthesis. Large numbers of probes (>100) corresponding to transcription, protein biosynthesis and intracellular signalling showed >2-fold differential expression at one of the time-points. Furthermore, 60 Gene Ontology terms were affected significantly (z score > 2). Conversely, serum biochemistry and histological evaluation of hepatic tissue showed no signs of stress. These gene expression alterations provide the first report of early hepatic response after an acute dose of bulaquine in mice liver; however, absence of traditional markers of hepatic stress might suggest a general hepatic response inherent in these transcriptional changes. Interestingly, the total number of affected probes was less as compared to that previously reported for primaquine.

Original languageEnglish (US)
Pages (from-to)522-529
Number of pages8
JournalBasic and Clinical Pharmacology and Toxicology
Volume103
Issue number6
DOIs
StatePublished - Dec 2008
Externally publishedYes

Fingerprint

Primaquine
Liver
Genes
Gene expression
Biochemistry
Biosynthesis
Transcription
Plasmodium ovale
Ontology
Gene Expression
Plasmodium vivax
Gene Ontology
Tissue
Plasmodium
Derivatives
Protein Biosynthesis
bulaquine
India
Pharmaceutical Preparations
Proteins

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Identification of differentially expressed genes after acute exposure to bulaquine (CDRI 80/53) in mice liver. / Noel, Sanjeev; Sharma, Sharad; Shankar, Rishi; Rath, Srikanta Kumar.

In: Basic and Clinical Pharmacology and Toxicology, Vol. 103, No. 6, 12.2008, p. 522-529.

Research output: Contribution to journalArticle

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