Nano-intercalated rhodanese in cyanide antagonism.
Present studies have focused on nano-intercalated rhodanese in combination with sulfur donors to prevent cyanide lethality in a prophylactic mice model for future development of an effective cyanide antidotal system. Our approach is based on the idea of converting cyanide to the less toxic thiocyanate before it reaches the target organs by utilizing sulfurtransferases (e.g., rhodanese) and sulfur donors in a close proximity by injecting them directly into the blood stream. The inorganic thiosulfate (TS) and the garlic component diallydisulfide (DADS) were compared as sulfur donors with the nano-intercalated rhodanese in vitro and in vivo. The in vivo and in vitro experiments showed that DADS is not a more efficient sulfur donor than TS. However, the utilization of external rhodanese significantly enhanced the in vivo efficacy of both sulfur donor-nitrite combinations, indicating the potential usefulness of enzyme nano-delivery systems in developing antidotal therapeutic agents.
Petrikovics
Ilona
I
U.S. Army Medical Research Institute of Chemical Defense, Maryland, USA. ixp004@shsu.edu
Baskin
Steven I
SI
Beigel
Keith M
KM
Schapiro
Benjamin J
BJ
Rockwood
Gary A
GA
Manage
Ananda B W
AB
Budai
Marianna
M
Szilasi
Maria
M
D000498:Allyl Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D000818:Animals; D000931:Antidotes / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D050091:Dendrimers / Q000737:chemistry*; D004220:Disulfides / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry*; D004357:Drug Synergism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010080:Oxazoles / Q000737:chemistry; D011041:Poisoning / Q000517:prevention & control; D011073:Polyamines; D011108:Polymers / Q000737:chemistry; D011190:Potassium Cyanide / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000506:poisoning*; D013884:Thiosulfate Sulfurtransferase / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D013885:Thiosulfates / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use
D000498:Allyl Compounds; D000931:Antidotes; D050091:Dendrimers; D004220:Disulfides; D004337:Drug Carriers; D010080:Oxazoles; D011073:Polyamines; D011108:Polymers; D013885:Thiosulfates; C511916:poly(2-ethyl-2-oxazoline); C028009:diallyl disulfide; D013884:Thiosulfate Sulfurtransferase; D011190:Potassium Cyanide