Events Calendar

10 Aug
Kimberly Garrett Dissertation Defense
Event Type

Defenses

Target Audience

Staff, Alumni, Faculty, Graduate Students, Postdocs

University Unit
Department of Environmental and Occupational Health
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Kimberly Garrett Dissertation Defense

Title: Potential Antidotes to Phosphine Poisoning

Abstract:

Globally, phosphine gas (PH3) released from metal phosphides is responsible for more poisonings (both intentional and accidental) than any other chemical agent. Metal phosphides (e.g. Ca3P2, AlP) produce PH3 through hydrolysis and can react with moisture in ambient air. PH3 is used as a fumigant pesticide and is a workplace hazard in agriculture, shipping, pest control, and the semiconductor industry where it is used as a doping agent. However, the majority of phosphine exposures are suicidal in nature. There is currently no antidote to PH3 available. Most purposeful PH3 poisonings occur through the ingestion of metal phosphides, which results in continuous exposure to PH3 gas. Therefore, it is beneficial to develop an antidote with both prophylactic and therapeutic activity. PH3 is associated with the inhibition of mitochondrial respiration at complex IV, cytochrome c oxidase, but its scope of effects is not fully understood. Methemoglobinemia and hemolysis have been reported in cases of PH3 poisoning and are negatively associated with survival. The relationship between PH3 and the blood remains undefined. We proposed and screened transition-metal based complexes as potential antidotes to PH3 in an insect and mouse model. Based on inorganic principles, we hypothesized that Au(I) and Ag(I) complexes would work as effective decorporating antidotes against PH3. We also tested some Co(II/III) complexes, shown to be effective against other complex IV inhibitors, against PH3. Using spectroscopic methods and high-resolution respirometry, we investigated the molecular interactions of the most promising potential antidotes with PH3 and studied the impacts of PH3 on blood, both in vitro and in vivo.  In this work, we describe a novel method for studying PH3 toxicity and potential antidotes using Galleria mellonella larvae, the varied activity of Au(I), Ag(I), and Co(II/III) complexes against phosphine in vivo, the ameliorative potential of catalytic PH3 oxidation, and the contribution of methemoglobinemia and hemolysis to PH3 toxicity with the aim of advancing the development of antidotes to PH3 poisoning.  

Dial-In Information

Please email bms85@pitt.edu for Zoom link and password

Tuesday, August 10 at 9:00 a.m. to 12:00 p.m.

Virtual Event

Kimberly Garrett Dissertation Defense

Title: Potential Antidotes to Phosphine Poisoning

Abstract:

Globally, phosphine gas (PH3) released from metal phosphides is responsible for more poisonings (both intentional and accidental) than any other chemical agent. Metal phosphides (e.g. Ca3P2, AlP) produce PH3 through hydrolysis and can react with moisture in ambient air. PH3 is used as a fumigant pesticide and is a workplace hazard in agriculture, shipping, pest control, and the semiconductor industry where it is used as a doping agent. However, the majority of phosphine exposures are suicidal in nature. There is currently no antidote to PH3 available. Most purposeful PH3 poisonings occur through the ingestion of metal phosphides, which results in continuous exposure to PH3 gas. Therefore, it is beneficial to develop an antidote with both prophylactic and therapeutic activity. PH3 is associated with the inhibition of mitochondrial respiration at complex IV, cytochrome c oxidase, but its scope of effects is not fully understood. Methemoglobinemia and hemolysis have been reported in cases of PH3 poisoning and are negatively associated with survival. The relationship between PH3 and the blood remains undefined. We proposed and screened transition-metal based complexes as potential antidotes to PH3 in an insect and mouse model. Based on inorganic principles, we hypothesized that Au(I) and Ag(I) complexes would work as effective decorporating antidotes against PH3. We also tested some Co(II/III) complexes, shown to be effective against other complex IV inhibitors, against PH3. Using spectroscopic methods and high-resolution respirometry, we investigated the molecular interactions of the most promising potential antidotes with PH3 and studied the impacts of PH3 on blood, both in vitro and in vivo.  In this work, we describe a novel method for studying PH3 toxicity and potential antidotes using Galleria mellonella larvae, the varied activity of Au(I), Ag(I), and Co(II/III) complexes against phosphine in vivo, the ameliorative potential of catalytic PH3 oxidation, and the contribution of methemoglobinemia and hemolysis to PH3 toxicity with the aim of advancing the development of antidotes to PH3 poisoning.  

Dial-In Information

Please email bms85@pitt.edu for Zoom link and password

Tuesday, August 10 at 9:00 a.m. to 12:00 p.m.

Virtual Event

Event Type

Defenses

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