Nitrosative stress induced cytotoxicity in Giardia intestinalis.
OBJECTIVE
To investigate the antigiardial properties of the nitrosating agents: sodium nitrite, sodium nitroprusside and Roussin's black salt.


RESULTS
Use of confocal laser scanning microscopy and flow cytometry indicated permeabilization of the plasma membrane to the anionic fluorophore, DiBAC4(3) [bis(1,3-dibutylbarbituric acid) trimethine oxonol]. Loss of plasma membrane electrochemical potential was accompanied by loss of regulated cellular volume control. Changes in ultrastructure revealed by electron microscopy and capacity for oxygen consumption, were also consequences of nitrosative stress. Roussin's black salt (RBS), active at micromolar concentrations was the most potent of the three agents tested.


CONCLUSIONS
These multitargeted cytotoxic agents affected plasma membrane functions, inhibited cellular functions in Giardia intestinalis and led to loss of viability.


CONCLUSIONS
Nitrosative damage, as an antigiardial strategy, may have implications for development of chemotherapy along with suggesting natural host defence mechanisms.
Lloyd
D
D
Department of Microbiology, Cardiff University, Cardiff, Wales, UK. lloydd@cardiff.ac.uk
Harris
J C
JC
Maroulis
S
S
Mitchell
A
A
Hughes
M N
MN
Wadley
R B
RB
Edwards
M R
MR
D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D005407:Flagella / Q000187:drug effects; D016829:Giardia lamblia / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D066298:In Vitro Techniques; D058085:Iron Compounds / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D012977:Sodium Nitrite / Q000494:pharmacology
D000981:Antiprotozoal Agents; D058085:Iron Compounds; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D009599:Nitroprusside; C078952:Roussin's Black Salt; D012977:Sodium Nitrite