Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Language
Publication year range
1.
Article in English | MEDLINE | ID: mdl-28589096

ABSTRACT

We have recently reported that Entamoeba histolytica trophozoites can adapt to toxic levels of the nitric oxide (NO) donor, S-nitrosoglutathione (GSNO). Even if the consequences of this adaptation on the modulation of gene expression in NO-adapted trophozoites (NAT) have been previously explored, insight on S-nitrosylated (SNO) proteins in NAT is missing. Our study aims to fill this knowledge gap by performing a screening of SNO proteins in NAT. Employing SNO resin-assisted capture (RAC), we identified 242 putative SNO proteins with key functions in calcium binding, enzyme modulation, redox homeostasis, and actin cytoskeleton. Of the SNO proteins in NAT, proteins that are associated with actin family cytoskeleton protein are significantly enriched. Here we report that the formation of actin filaments (F-actin) is impaired in NAT. Consequently, the ability of NAT to ingest erythrocytes and their motility and their cytopathic activity are impaired. These phenotypes can be imitated by treating control parasite with cytochalasin D (CytD), a drug that binds to F-actin polymer and prevent polymerization of actin monomers. Removal of GSNO from the culture medium of NAT restored the sensitivity of the parasite to nitrosative stress (NS) and its ability to form F-actin formation and its virulence. These results establish the central role of NO in shaping the virulence of the parasite through its effect on F-actin formation and highlight the impressive ability of this parasite to adapt to NS.


Subject(s)
Actins/metabolism , Entamoeba histolytica/chemistry , Entamoeba histolytica/metabolism , Nitrosative Stress , Protozoan Proteins/metabolism , S-Nitrosothiols/chemistry , Virulence , Actin Cytoskeleton/metabolism , Actins/ultrastructure , Cell Movement/physiology , Cysteine/analogs & derivatives , Entamoeba histolytica/drug effects , Entamoeba histolytica/pathogenicity , Erythrocytes/parasitology , Gene Expression , Microscopy, Confocal , Nitric Oxide/pharmacology , Proteolysis , Protozoan Proteins/genetics , Trophozoites/metabolism , Virulence/drug effects
2.
BMC Pharmacol Toxicol ; 18(1): 13, 2017 03 14.
Article in English | MEDLINE | ID: mdl-28288687

ABSTRACT

BACKGROUND: Better and safer antidotes against cyanide poisoning are needed. Prior study has shown a favorable effect of isosorbide dinitrate (ISDN) on the survival of cyanide-poisoned rabbits when administered as early as 1 min after poisoning. The aim of the current study was to further evaluate the efficacy of intravenous ISDN administered in clinically relevant timing for first responders. METHODS: A comparative animal study using 24 rabbits in 4 randomized study groups was performed. Animals were poisoned with intravenous potassium cyanide (1 mg/kg). Animals in Group 1 served as controls and received no treatment. Groups 2-4 animals were treated intravenously with ISDN (50 µg/kg) after poisoning; one group after 3 min, another group after 5 min and the last after 7 min. Animals were observed for 30 min after poisoning. The study endpoints included survival rate, clinical status, blood pressure, pulse per minute, blood lactate and pH. RESULTS: Five of 6 animals (83.3%) from every treatment group survived the whole observation period while all control untreated animals died. All the rabbits collapsed immediately after exposure, showing rapidly deteriorated vital signs with lactic metabolic acidosis (peak blood lactate levels of 18.1 to 19.0 mmol/L on average at 10 min post exposure). Vital signs, clinical scores, and blood gases of treated rabbits gradually improved. CONCLUSION: Poisoned rabbits showed improved short-term survival following the administration of ISDN up to 7 min after lethal cyanide poisoning of. We see a potential for ISDN as an antidote against cyanide poisoning.


Subject(s)
Isosorbide Dinitrate/administration & dosage , Poisoning/drug therapy , Potassium Cyanide/poisoning , Administration, Intravenous , Animals , Drug Administration Schedule , Poisoning/blood , Poisoning/mortality , Potassium Cyanide/blood , Rabbits , Random Allocation , Survival Rate/trends , Treatment Outcome , Vasodilator Agents/administration & dosage
SELECTION OF CITATIONS
SEARCH DETAIL
...