Someone sent me a link to a very interesting article on NASH/MASH.
My response -
What is the mechanism of action for Ferrostatin-1?
Arachidonoyl-PE expression is induced by excessive intracellular CA2+ and is converted from arachidonic acid. Arachidonoyl-PE increases both NOX and ROS production promoting an inflammatory state, cell death and mitochondrial dysfunction. CA2+, arachidonic acid, NOX and ROS all downregulated by leronlimab. Leronlimab also downregulates a number of other pro-inflammatory pathways. It's pretty straightforward that as in many other diseases over-activation of the immune system is the culprit.
From the original study -
GPX4 inhibits ferroptosis induced cell death.
GPX4 is highly downregulated by COX2 (an inflammatory gene). COX2 is increased by the Akt/PI3k/mTOR pathway's activation of IL-1b and TNF-a. Leronlimab would reverse the downregulation of GPX4.
My response -
Quote:In experiments using mice and liver tissue from humans, the researchers identified how the aging process prompts certain liver cells to die off. They were then able to reverse the process in the animals with an investigational drug.
The finding, which appears in the journal Nature Aging, holds high promise for the millions of people who have some degree of liver damage – livers that are essentially old due to the metabolic stresses of high cholesterol, obesity, diabetes or other factors
Importantly, key genes in the livers of people with MASLD were highly activated to promote cell death through ferroptosis. This gave the researchers a definitive target.
“There are things we can use to block that,” Diehl said.
Again turning to mice, the researchers fed young and old mice diets that caused them to develop MASLD. They then gave half the animals a placebo drug and the other half a drug called Ferrostatin-1, which inhibits the cell death pathway.
Upon analysis after treatment, the livers of the animals given Ferrostatin-1 looked biologically like young, healthy livers -- even in the old animals that were kept on the disease-inducing diet.
https://corporate.dukehealth.org/news/study-s...reversible
What is the mechanism of action for Ferrostatin-1?
Quote:
Ferrostatin-1 binds and selectively inhibits arachidonoyl-PE oxidation by 15-LOX/PEBP1.
Arachidonoyl-PE expression is induced by excessive intracellular CA2+ and is converted from arachidonic acid. Arachidonoyl-PE increases both NOX and ROS production promoting an inflammatory state, cell death and mitochondrial dysfunction. CA2+, arachidonic acid, NOX and ROS all downregulated by leronlimab. Leronlimab also downregulates a number of other pro-inflammatory pathways. It's pretty straightforward that as in many other diseases over-activation of the immune system is the culprit.
From the original study -
Quote:One of the recently identified programs, ferroptosis, is triggered in cells by the unbalanced redox regulation of three major metabolic pathways related to iron, thiols, and lipids . The role of thiols in the scheme of this irrevocable penalty has been established as the deficiency of the glutathione peroxidase 4 (GPX4) and/or the reduced glutathione (GSH) concentration
https://www.sciencedirect.com/science/article...1720309496
GPX4 inhibits ferroptosis induced cell death.
GPX4 is highly downregulated by COX2 (an inflammatory gene). COX2 is increased by the Akt/PI3k/mTOR pathway's activation of IL-1b and TNF-a. Leronlimab would reverse the downregulation of GPX4.
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