An oxygen diffusion-enhancing compound is any substance that increases the availability of oxygen in
body tissues by influencing the
molecular structure of water in
blood plasma
Blood plasma is a light amber-colored liquid component of blood in which blood cells are absent, but contains proteins and other constituents of whole blood in suspension. It makes up about 55% of the body's total blood volume. It is the ...
and thereby promoting the movement (
diffusion
Diffusion is the net movement of anything (for example, atoms, ions, molecules, energy) generally from a region of higher concentration to a region of lower concentration. Diffusion is driven by a gradient in Gibbs free energy or chemical p ...
) of oxygen through plasma.
Oxygen diffusion-enhancing compounds have shown promise in the treatment of conditions associated with
hypoxia (a lack of oxygen in tissues) and
ischemia (a lack of oxygen in the circulating blood supply).
Such conditions include
hemorrhagic shock,
myocardial infarction
A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which ...
(heart attack), and
stroke.
Types
One of the first substances that was reported to produce an oxygen diffusion-enhancing effect was
crocetin, a carotenoid that occurs naturally in plants such as ''
crocus sativus'', and is related to another carotenoid,
saffron
Saffron () is a spice derived from the flower of ''Crocus sativus'', commonly known as the "saffron crocus". The vivid crimson stigma (botany), stigma and stigma (botany)#style, styles, called threads, are collected and dried for use mainly ...
. Saffron has been used culturally (e.g., as a dye) and medicinally since ancient times.
Trans sodium crocetinate (TSC), a synthetic drug containing the carotenoid structure of trans crocetin has been extensively investigated in animal disease models and in human clinical trials.
Clinical trials of TSC have focused on testing the compound's effectiveness in sensitizing hypoxic cancer cells to radiation therapy in patients with
glioblastoma, an aggressive form of brain cancer.
TSC, which is being developed by
Diffusion Pharmaceuticals, has been shown to enhance the oxygenation of hypoxic tumor tissue and belongs to a subclass of oxygen diffusion-enhancing compounds known as bipolar trans carotenoid salts.
Diffusion Pharmaceuticals is currently investigating the use of
trans sodium crocetinate in the treatment of
COVID-19
Coronavirus disease 2019 (COVID-19) is a contagious disease caused by a virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first known case was identified in Wuhan, China, in December 2019. The disease quickl ...
, acute
stroke, and solid
cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bl ...
ous tumors.
Mechanism of action
Oxygen diffusion-enhancing compounds are thought to act by exerting
hydrophobic
In chemistry, hydrophobicity is the physical property of a molecule that is seemingly repelled from a mass of water (known as a hydrophobe). In contrast, hydrophiles are attracted to water.
Hydrophobic molecules tend to be nonpolar and, ...
forces that interact with water molecules.
These interactions result in greater
hydrogen bond
In chemistry, a hydrogen bond (or H-bond) is a primarily electrostatic force of attraction between a hydrogen (H) atom which is covalently bound to a more electronegative "donor" atom or group (Dn), and another electronegative atom bearing ...
ing among water molecules, which constitute the majority of the blood plasma medium.
As hydrogen bonding increases, the overall molecular structure of water in the plasma becomes more lattice-like, a phenomenon known as structure building.
Structure building reduces resistance to the movement of oxygen through plasma via diffusion.
Since blood plasma offers the major barrier for oxygen to move from the
red blood cell
Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...
s and into the tissues,
the more structured character of water imparted by the oxygen diffusion-enhancing compound will enhance movement into tissues.
Computer simulations have shown that TSC specifically can increase the transport of oxygen through water by as much as 30 percent.
References
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Oxygen
Diffusion
Chemical compounds
Biochemistry
Drugs by mechanism of action