ARS Heath Family Project Grant
Does pyrroloquinoline quinone (PQQ) have potential as a novel therapy to prevent oxidative stress and mitochondrial dysfunction under conditions of sepsis?
Professor Helen Galley
Background
Sepsis, or severe infection kills 37,000 people every year in the UK. The main cause of death is organ failure. Mitochondria are structures inside cells where energy is made and if they are damaged they are unable to make enough energy. Such damage to mitochondria can alter cell function, and contributes to organ failure. Melatonin is a naturally occurring substance which you probably know about in relation to jet lag, but which can also protect mitochondria. PQQ is a non-toxic substance made by harmless bacteria found on the roots of vegetable plants which can also protect mitochondria from damage. We think that PQQ may be better than melatonin, but we don't know if it specifically protects inside mitochondria and whether it is effective under conditions mimicking sepsis.
Aim
We propose to examine the effects of PQQ and melatonin to see which is best at protecting cells against the damage caused by sepsis. By exposing cells to conditions similar to sepsis we can test the effect of these molecules on different aspects of mitochondrial and cell function.
Methodology
We will use whole blood from volunteers and the cells which line veins and arteries called endothelial cells. All of these cells are important in fighting infection. We will use healthy volunteers to obtain the whole blood and a human cell line for the endothelial cells. Cells will be exposed to substances which mimic what happens in sepsis. We will then assess the effect of PQQ and melatonin on different aspects of mitochondrial and cell function.
Expected outcomes
This study will enable us to test whether PQQ is better than melatonin at preventing damage caused by sepsis and whether it can specifically protect mitochondria. This will be the first step in characterizing PQQ as a potential novel treatment for sepsis.
