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Piperaquine and Lumefantrine resistance in Plasmodium berghei ANKA associated with increased expression of Ca2+/H+ antiporter and glutathione associated enzymes
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Pharmaceutical Regulatory Affairs: Open Access

ISSN: 2167-7689

Open Access

Piperaquine and Lumefantrine resistance in Plasmodium berghei ANKA associated with increased expression of Ca2+/H+ antiporter and glutathione associated enzymes


5th International Conference and Exhibition on Pharmaceutical Regulatory Affairs

August 03-05, 2015 Orlando, USA

Daniel Kiboi1, 2, Beatrice Irungu2, Jennifer Orwa2, Luna Kamau2, Lynette Isabella Ochola-Oyier2, Joseph Ng?¡ng?¡1 and Alexis Nzila3

1Jomo Kenyatta University of Agriculture and Technology, Kenya 2Kenya Medical Research Institute ( KEMRI), Kenya 3King Fahd University of Petroleum and Minerals, Kingdom of Saudi Arabia

Posters-Accepted Abstracts: Pharmaceut Reg Affairs

Abstract :

We investigated the mechanisms of resistance of two antimalarial drugs Piperaquine (PQ) and Lumefantrine (LM) using the rodent parasite Plasmodium berghei as a surrogate of the human parasite, Plasmodium falciparum. We analysed the whole coding sequence of Plasmodium berghei chloroquine resistance transporter (Pbcrt) and Plasmodium berghei multidrug resistance gene-1 (Pbmdr-1) for polymorphisms. These genes are associated with quinoline resistance in Plasmodium falciparum. No polymorphic changes were detected in the coding sequences of Pbcrt and Pbmdr-1 or in the mRNA transcript levels of Pbmdr-1. However, our data demonstrated that PQ and LM resistance is achieved by multiple mechanisms that include elevated mRNA transcript levels of V-type H+ pumping pyrophosphatase (vp2), Ca2+/H+ antiporter (vcx1), gamma glutamylcysteine synthetase (ggcs) and glutathione-Stransferase (gst) genes. These mechanisms are also known to contribute to chloroquine resistance in P. falciparum and rodent malaria parasites. The increase in â??ggcsâ?? and â??gstâ?? transcript levels were accompanied by high glutathione (GSH) levels and elevated activity of glutathione-S-transferase (GST) enzyme. Taken together, these results demonstrate that Pbcrt and Pbmdr-1 are not associated with PQ and LM resistance in P. berghei ANKA, while vp2, vcx1, â??ggcsâ?? and â??gstâ?? may mediate resistance directly or modulate functional mutations in other unknown genes.

Biography :

Email: dmuthui@jkuat.ac.ke

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