A Lipid-Based Oral Supplement Protects Skin Cells in Culture from Ultraviolet Light and Activates Antioxidant and Anti-Inflammatory Mechanisms

Hall, Steven R.; Reid, Anna‐Jean; Eng, Jasmine; McKeown, Brendan; St‐Onge, Marc; Goralski, Kerry B.

doi:10.33211/jnhpr.10

Cited by 2 publications

(2 citation statements)

References 49 publications

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“…The highest concentration of each drug that did not significantly reduce cell viability when compared to the vehicle control (labelled ‘0’) was determined to be the MTC. Then, to ensure that cells would be treated with a sub-toxic amount of drug in the venom-inhibition experiments, one half of this dose (MTC ½ ) was selected for the venom-drug co-treatment experiments 49,50 . The MTC ½ for DMPS, marimastat, and varespladib used in the following experiments were 625, 2.56, and 128 μM, respectively ( Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

Repurposed drugs and their combinations prevent morbidity-inducing dermonecrosis caused by diverse cytotoxic snake venoms

Hall

Rasmussen²,

Dawson

et al. 2022

Preprint

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Morbidity from snakebite envenoming affects approximately 400,000 people annually. Tissue damage at the bite-site often leaves victims with catastrophic life-long injuries and is largely untreatable by currently available antivenoms. Repurposing small molecule drugs that inhibit specific snake venom toxins offers a potential new treatment strategy for tackling this neglected tropical disease. Using human skin cell assays as an initial model for snakebite-induced dermonecrosis, we show that the repurposed drugs 2,3-dimercapto-1-propanesulfonic acid (DMPS), marimastat, and varespladib, alone or in combination, reduce the cytotoxic potency of a broad range of medically important snake venoms up to 5.7-fold. Thereafter, using a preclinical murine model of dermonecrosis, we demonstrate that the dual therapeutic combinations of DMPS or marimastat with varespladib potently inhibit the dermonecrotic activity of three geographically distinct and medically important snake venoms. These findings strongly support the future translation of repurposed drug combinations as broad-spectrum therapeutics for preventing morbidity caused by snakebite.

show abstract

Section: Resultsmentioning

confidence: 99%

Repurposed drugs and their combinations prevent morbidity-inducing dermonecrosis caused by diverse cytotoxic snake venoms

Hall

Rasmussen²,

Dawson

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…The highest concentration of each drug that did not significantly reduce cell viability when compared to the vehicle control (labelled '0') was determined to be the MTC. Then, to ensure that cells would be treated with a sub-toxic amount of drug in the venom-inhibition experiments, one half of this dose (MTC ½ ) was selected for the venom-drug co-treatment experiments 57,58 . The MTC ½ for DMPS, marimastat, and varespladib used in the following experiments were 625, 2.56, and 128 µM, respectively (Supplementary Fig.…”

Section: Dmps and Marimastat Reduce The Loss Of Adherent Cell Viabili...mentioning

confidence: 99%

Repurposed drugs and their combinations prevent morbidity-inducing dermonecrosis caused by diverse cytotoxic snake venoms

Hall,

Rasmussen,

Crittenden

et al. 2023

Nat Commun

Self Cite

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Morbidity from snakebite envenoming affects approximately 400,000 people annually. Tissue damage at the bite-site often leaves victims with catastrophic life-long injuries and is largely untreatable by current antivenoms. Repurposed small molecule drugs that inhibit specific snake venom toxins show considerable promise for tackling this neglected tropical disease. Using human skin cell assays as an initial model for snakebite-induced dermonecrosis, we show that the drugs 2,3-dimercapto-1-propanesulfonic acid (DMPS), marimastat, and varespladib, alone or in combination, inhibit the cytotoxicity of a broad range of medically important snake venoms. Thereafter, using preclinical mouse models of dermonecrosis, we demonstrate that the dual therapeutic combinations of DMPS or marimastat with varespladib significantly inhibit the dermonecrotic activity of geographically distinct and medically important snake venoms, even when the drug combinations are delivered one hour after envenoming. These findings strongly support the future translation of repurposed drug combinations as broad-spectrum therapeutics for preventing morbidity caused by snakebite.

show abstract

A Lipid-Based Oral Supplement Protects Skin Cells in Culture from Ultraviolet Light and Activates Antioxidant and Anti-Inflammatory Mechanisms

Cited by 2 publications

References 49 publications

Repurposed drugs and their combinations prevent morbidity-inducing dermonecrosis caused by diverse cytotoxic snake venoms

Repurposed drugs and their combinations prevent morbidity-inducing dermonecrosis caused by diverse cytotoxic snake venoms

Repurposed drugs and their combinations prevent morbidity-inducing dermonecrosis caused by diverse cytotoxic snake venoms

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