Sodium antimony gluconate induces generation of reactive oxygen species and nitric oxide via phosphoinositide 3-kinase and mitogen-activated protein kinase activation in Leishmania donovani-infected macrophages.

Antimicrobial Agents and Chemotherapy
Jayati Mookerjee BasuSyamal Roy

Abstract

Pentavalent antimony complexes, such as sodium stibogluconate and sodium antimony gluconate (SAG), are still the first choice for chemotherapy against various forms of leishmaniasis, including visceral leishmaniasis, or kala-azar. Although the requirement of a somewhat functional immune system for the antileishmanial action of antimony was reported previously, the cellular and molecular mechanism of action of SAG was not clear. Herein, we show that SAG induces extracellular signal-regulated kinase 1 (ERK-1) and ERK-2 phosphorylation through phosphoinositide 3-kinase (PI3K), protein kinase C, and Ras activation and p38 mitogen-activated protein kinase (MAPK) phosphorylation through PI3K and Akt activation. ERK-1 and ERK-2 activation results in an increase in the production of reactive oxygen species (ROS) 3 to 6 h after SAG treatment, while p38 MAPK activation and subsequent tumor necrosis factor alpha release result in the production of nitric oxide (NO) 24 h after SAG treatment. Thus, this study has provided the first evidence that SAG treatment induces activation of some important components of the intracellular signaling pathway, which results in an early wave of ROS-dependent parasite killing and a stronger late wave of NO-...Continue Reading

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Citations

Jul 30, 2011·Parasitology Research·Khatima Aït-OudhiaDenis Sereno
May 28, 2011·Biological Trace Element Research·Claus HansenStefan Stürup
Jan 24, 2013·Proceedings of the National Academy of Sciences of the United States of America·Budhaditya MukherjeeSyamal Roy
Apr 6, 2011·Antimicrobial Agents and Chemotherapy·Arpita KulshresthaPoonam Salotra
Dec 7, 2007·Antimicrobial Agents and Chemotherapy·Jayati Mookerjee BasuSyamal Roy
Apr 11, 2013·Antimicrobial Agents and Chemotherapy·Manu De RyckerDavid W Gray
Jan 15, 2011·Journal of Leukocyte Biology·David A WinkCarol A Colton
Sep 3, 2010·PloS One·Manu VanaerschotSaskia Decuypere
Sep 10, 2013·Research in Veterinary Science·D B BentoP R Romão
Nov 30, 2011·Antioxidants & Redox Signaling·Chinmay Pal, Uday Bandyopadhyay
Sep 7, 2012·Critical Reviews in Microbiology·Manu VanaerschotJean-Claude Dujardin
Mar 9, 2012·Expert Review of Anti-infective Therapy·Marie-Thérèse Labro
Oct 1, 2014·Drug and Chemical Toxicology·Ludymila Furtado CantanhêdeSilma Regina Ferreira Pereira
Jul 15, 2015·International Journal of Biological Macromolecules·Monica Mendes Kangussu-MarcolinoGuilhermina Rodrigues Noleto
Nov 18, 2011·Molecular Biology International·Arun Kumar HaldarSyamal Roy
Mar 10, 2016·Infectious Diseases of Poverty·Om Prakash SinghShyam Sundar
Jun 9, 2009·Journal of Neurochemistry·Debapriya GhoshAnirban Basu

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