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Vol. 23, No. 1-3, 2009
Issue release date: 2009
Cell Physiol Biochem 2009;23:191–198
(DOI:10.1159/000204107)

Influence of Paclitaxel on Parasitemia and Survival of Plasmodium berghei Infected Mice

Koka S.1,* · Bobbala D.1,* · Lang C.1 · Boini K.M.1 · Huber S.M.1,2 · Lang F.1
1Department of Physiology and2Radiation Oncology, University of Tübingen,*contributed equally and thus share first authorship
email Corresponding Author

Abstract

Paclitaxel triggers suicidal erythrocyte death or eryptosis, characterized by exposure of phosphatidylserine at the erythrocyte surface and cell shrinkage. Eryptosis of infected erythrocytes may delay development of parasitemia and thus favourably influence the course of malaria. The present study explored whether paclitaxel influences in vitro parasite growth and eryptosis of Plasmodium falciparum infected human erythrocytes and in vivo parasitemia and survival of Plasmodium berghei infected mice. Phosphatidylserine exposing erythrocytes were identified utilizing annexin V binding and erythrocyte volume was estimated from forward scatter in FACS analysis. In vitro infection of human erythrocytes with P. falciparum increased annexin binding and decreased forward scatter, effects augmented in the presence of paclitaxel (≥0.01 μM). Paclitaxel (≥0.01 μM) significantly decreased intraerythrocytic DNA/RNA content and in vitro parasitemia. In Plasmodium berghei infected mice parasitemia was significantly decreased (from 55.8% to 28.6% of circulating erythrocytes 20 days after infection) and mouse survival significantly enhanced (from 0% to 69.23% 25 days after infection) by administration of 8.5 mg/kg.b.w. of paclitaxel intraperitoneally from the eighth day of infection. In conclusion, paclitaxel decreases parasitemia and enhances survival of P. berghei infected mice, an effect, which may be due to stimulation of eryptosis and/or a direct toxic effect on the parasite.


 Outline


 goto top of outline Key Words

  • Malaria
  • Cell volume
  • Phosphatidylserine
  • Apoptosis
  • Cell death
  • Eryptosis
  • Taxol
  • Docetaxel

 goto top of outline Abstract

Paclitaxel triggers suicidal erythrocyte death or eryptosis, characterized by exposure of phosphatidylserine at the erythrocyte surface and cell shrinkage. Eryptosis of infected erythrocytes may delay development of parasitemia and thus favourably influence the course of malaria. The present study explored whether paclitaxel influences in vitro parasite growth and eryptosis of Plasmodium falciparum infected human erythrocytes and in vivo parasitemia and survival of Plasmodium berghei infected mice. Phosphatidylserine exposing erythrocytes were identified utilizing annexin V binding and erythrocyte volume was estimated from forward scatter in FACS analysis. In vitro infection of human erythrocytes with P. falciparum increased annexin binding and decreased forward scatter, effects augmented in the presence of paclitaxel (≥0.01 μM). Paclitaxel (≥0.01 μM) significantly decreased intraerythrocytic DNA/RNA content and in vitro parasitemia. In Plasmodium berghei infected mice parasitemia was significantly decreased (from 55.8% to 28.6% of circulating erythrocytes 20 days after infection) and mouse survival significantly enhanced (from 0% to 69.23% 25 days after infection) by administration of 8.5 mg/kg.b.w. of paclitaxel intraperitoneally from the eighth day of infection. In conclusion, paclitaxel decreases parasitemia and enhances survival of P. berghei infected mice, an effect, which may be due to stimulation of eryptosis and/or a direct toxic effect on the parasite.

Copyright © 2009 S. Karger AG, Basel


 goto top of outline Author Contacts

Prof. Dr. Florian Lang
Physiologisches Institut, der Universität Tübingen
Gmelinstr. 5, 72076 Tübingen (Germany)
Tel. +49 7071 29 72194, Fax: +49 7071 29 5618
E-Mail florian.lang@uni-tuebingen.de


 goto top of outline Article Information

Accepted: December 04, 2008
Published online: February 18, 2009
Number of Print Pages : 8


 goto top of outline Publication Details

Cellular Physiology and Biochemistry (International Journal of Experimental Cellular Physiology, Biochemistry andPharmacology)

Vol. 23, No. 1-3, Year 2009 (Cover Date: 2009)

Journal Editor: F. Lang, Tübingen
ISSN: 1015–8987 (Print), eISSN: 1421–9778 (Online)

For additional information: http://www.karger.com/journals/cpb


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

Paclitaxel triggers suicidal erythrocyte death or eryptosis, characterized by exposure of phosphatidylserine at the erythrocyte surface and cell shrinkage. Eryptosis of infected erythrocytes may delay development of parasitemia and thus favourably influence the course of malaria. The present study explored whether paclitaxel influences in vitro parasite growth and eryptosis of Plasmodium falciparum infected human erythrocytes and in vivo parasitemia and survival of Plasmodium berghei infected mice. Phosphatidylserine exposing erythrocytes were identified utilizing annexin V binding and erythrocyte volume was estimated from forward scatter in FACS analysis. In vitro infection of human erythrocytes with P. falciparum increased annexin binding and decreased forward scatter, effects augmented in the presence of paclitaxel (≥0.01 μM). Paclitaxel (≥0.01 μM) significantly decreased intraerythrocytic DNA/RNA content and in vitro parasitemia. In Plasmodium berghei infected mice parasitemia was significantly decreased (from 55.8% to 28.6% of circulating erythrocytes 20 days after infection) and mouse survival significantly enhanced (from 0% to 69.23% 25 days after infection) by administration of 8.5 mg/kg.b.w. of paclitaxel intraperitoneally from the eighth day of infection. In conclusion, paclitaxel decreases parasitemia and enhances survival of P. berghei infected mice, an effect, which may be due to stimulation of eryptosis and/or a direct toxic effect on the parasite.



 goto top of outline Author Contacts

Prof. Dr. Florian Lang
Physiologisches Institut, der Universität Tübingen
Gmelinstr. 5, 72076 Tübingen (Germany)
Tel. +49 7071 29 72194, Fax: +49 7071 29 5618
E-Mail florian.lang@uni-tuebingen.de


 goto top of outline Article Information

Accepted: December 04, 2008
Published online: February 18, 2009
Number of Print Pages : 8


 goto top of outline Publication Details

Cellular Physiology and Biochemistry (International Journal of Experimental Cellular Physiology, Biochemistry andPharmacology)

Vol. 23, No. 1-3, Year 2009 (Cover Date: 2009)

Journal Editor: F. Lang, Tübingen
ISSN: 1015–8987 (Print), eISSN: 1421–9778 (Online)

For additional information: http://www.karger.com/journals/cpb


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.