In-vitro mercaptopyruvate sulfurtransferase species comparison in humans and common laboratory animals

Bryant M. Moeller, Daune L. Crankshaw, Jacquie Briggs, Herbert T. Nagasawa, Steven Patterson

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Cyanide is a metabolic poison that inhibits cytochrome c oxidase. Its broad applications in manufacturing and history as an agent of warfare/terror highlight the limitations in approved cyanide antidotes for mass casualties. Sulfanegen, a pre-clinical antidote for cyanide poisoning, exploits an endogenous detoxification pathway and should be amenable to mass-casualty scenarios. Because human studies are unethical, determination of appropriate animal species as models in translational studies for FDA approval under the “Animal Rule” are critical. Here, we compared the specific activities of mercaptopyruvate sulfurtransferase (MST, required for sulfanegen's activity), across common laboratory models of cyanide intoxication, and humans. Human MST activities in erythrocytes (measured as micromole pyruvate/min/106 rbc) were closest to those of Swiss-Webster mice and NZW rabbits. Similar species were selected for a more detailed tissue-specific comparison of MST activities. NZW Rabbits were closest to humans in the liver and kidney mitochondrial fractions, the Swiss-Webster mouse was closest to humans in the liver cytosolic fraction, while C57BL/6 mouse was closest in the kidney cytosolic fraction. These data comparing MST activities in animal models will help justify the use of those specific animals per the animal rule. Interestingly, statistically significant differences were found in MST activities of liver mitochondria between human smokers and non-smokers (p = 0.0030).

Original languageEnglish (US)
Pages (from-to)64-68
Number of pages5
JournalToxicology Letters
Volume274
DOIs
StatePublished - May 15 2017

Fingerprint

Laboratory Animals
Cyanides
Animals
Liver
Mass Casualty Incidents
Antidotes
Rabbits
Kidney
Detoxification
Mitochondria
Liver Mitochondrion
Poisons
Military operations
Electron Transport Complex IV
Pyruvic Acid
Inbred C57BL Mouse
Human Activities
Poisoning
Animal Models
Erythrocytes

Keywords

  • Cyanide antidote
  • Mercaptopyruvate sulfurtransferase
  • Species comparison
  • Sulfanegen

PubMed: MeSH publication types

  • Journal Article

Cite this

In-vitro mercaptopyruvate sulfurtransferase species comparison in humans and common laboratory animals. / Moeller, Bryant M.; Crankshaw, Daune L.; Briggs, Jacquie; Nagasawa, Herbert T.; Patterson, Steven.

In: Toxicology Letters, Vol. 274, 15.05.2017, p. 64-68.

Research output: Contribution to journalArticle

Moeller, Bryant M. ; Crankshaw, Daune L. ; Briggs, Jacquie ; Nagasawa, Herbert T. ; Patterson, Steven. / In-vitro mercaptopyruvate sulfurtransferase species comparison in humans and common laboratory animals. In: Toxicology Letters. 2017 ; Vol. 274. pp. 64-68.
@article{49ce73fa27624a0dbbb0bdcb4e786830,
title = "In-vitro mercaptopyruvate sulfurtransferase species comparison in humans and common laboratory animals",
abstract = "Cyanide is a metabolic poison that inhibits cytochrome c oxidase. Its broad applications in manufacturing and history as an agent of warfare/terror highlight the limitations in approved cyanide antidotes for mass casualties. Sulfanegen, a pre-clinical antidote for cyanide poisoning, exploits an endogenous detoxification pathway and should be amenable to mass-casualty scenarios. Because human studies are unethical, determination of appropriate animal species as models in translational studies for FDA approval under the “Animal Rule” are critical. Here, we compared the specific activities of mercaptopyruvate sulfurtransferase (MST, required for sulfanegen's activity), across common laboratory models of cyanide intoxication, and humans. Human MST activities in erythrocytes (measured as micromole pyruvate/min/106 rbc) were closest to those of Swiss-Webster mice and NZW rabbits. Similar species were selected for a more detailed tissue-specific comparison of MST activities. NZW Rabbits were closest to humans in the liver and kidney mitochondrial fractions, the Swiss-Webster mouse was closest to humans in the liver cytosolic fraction, while C57BL/6 mouse was closest in the kidney cytosolic fraction. These data comparing MST activities in animal models will help justify the use of those specific animals per the animal rule. Interestingly, statistically significant differences were found in MST activities of liver mitochondria between human smokers and non-smokers (p = 0.0030).",
keywords = "Cyanide antidote, Mercaptopyruvate sulfurtransferase, Species comparison, Sulfanegen",
author = "Moeller, {Bryant M.} and Crankshaw, {Daune L.} and Jacquie Briggs and Nagasawa, {Herbert T.} and Steven Patterson",
year = "2017",
month = "5",
day = "15",
doi = "10.1016/j.toxlet.2017.04.005",
language = "English (US)",
volume = "274",
pages = "64--68",
journal = "Toxicology Letters",
issn = "0378-4274",
publisher = "Elsevier BV",

}

TY - JOUR

T1 - In-vitro mercaptopyruvate sulfurtransferase species comparison in humans and common laboratory animals

AU - Moeller, Bryant M.

AU - Crankshaw, Daune L.

AU - Briggs, Jacquie

AU - Nagasawa, Herbert T.

AU - Patterson, Steven

PY - 2017/5/15

Y1 - 2017/5/15

N2 - Cyanide is a metabolic poison that inhibits cytochrome c oxidase. Its broad applications in manufacturing and history as an agent of warfare/terror highlight the limitations in approved cyanide antidotes for mass casualties. Sulfanegen, a pre-clinical antidote for cyanide poisoning, exploits an endogenous detoxification pathway and should be amenable to mass-casualty scenarios. Because human studies are unethical, determination of appropriate animal species as models in translational studies for FDA approval under the “Animal Rule” are critical. Here, we compared the specific activities of mercaptopyruvate sulfurtransferase (MST, required for sulfanegen's activity), across common laboratory models of cyanide intoxication, and humans. Human MST activities in erythrocytes (measured as micromole pyruvate/min/106 rbc) were closest to those of Swiss-Webster mice and NZW rabbits. Similar species were selected for a more detailed tissue-specific comparison of MST activities. NZW Rabbits were closest to humans in the liver and kidney mitochondrial fractions, the Swiss-Webster mouse was closest to humans in the liver cytosolic fraction, while C57BL/6 mouse was closest in the kidney cytosolic fraction. These data comparing MST activities in animal models will help justify the use of those specific animals per the animal rule. Interestingly, statistically significant differences were found in MST activities of liver mitochondria between human smokers and non-smokers (p = 0.0030).

AB - Cyanide is a metabolic poison that inhibits cytochrome c oxidase. Its broad applications in manufacturing and history as an agent of warfare/terror highlight the limitations in approved cyanide antidotes for mass casualties. Sulfanegen, a pre-clinical antidote for cyanide poisoning, exploits an endogenous detoxification pathway and should be amenable to mass-casualty scenarios. Because human studies are unethical, determination of appropriate animal species as models in translational studies for FDA approval under the “Animal Rule” are critical. Here, we compared the specific activities of mercaptopyruvate sulfurtransferase (MST, required for sulfanegen's activity), across common laboratory models of cyanide intoxication, and humans. Human MST activities in erythrocytes (measured as micromole pyruvate/min/106 rbc) were closest to those of Swiss-Webster mice and NZW rabbits. Similar species were selected for a more detailed tissue-specific comparison of MST activities. NZW Rabbits were closest to humans in the liver and kidney mitochondrial fractions, the Swiss-Webster mouse was closest to humans in the liver cytosolic fraction, while C57BL/6 mouse was closest in the kidney cytosolic fraction. These data comparing MST activities in animal models will help justify the use of those specific animals per the animal rule. Interestingly, statistically significant differences were found in MST activities of liver mitochondria between human smokers and non-smokers (p = 0.0030).

KW - Cyanide antidote

KW - Mercaptopyruvate sulfurtransferase

KW - Species comparison

KW - Sulfanegen

UR - http://www.scopus.com/inward/record.url?scp=85018897258&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85018897258&partnerID=8YFLogxK

U2 - 10.1016/j.toxlet.2017.04.005

DO - 10.1016/j.toxlet.2017.04.005

M3 - Article

VL - 274

SP - 64

EP - 68

JO - Toxicology Letters

JF - Toxicology Letters

SN - 0378-4274

ER -