An oxygen diffusion-enhancing compound is any substance that increases the availability of oxygen in body tissues by influencing the

molecular structure Molecular geometry is the three-dimensional arrangement of the atoms that constitute a molecule. It includes the general shape of the molecule as well as bond lengths, bond angles, torsional angles and any other geometrical parameters that deter ...

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 intra ...

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 Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems wi ...

(a lack of oxygen in the circulating blood supply). Such conditions include

hemorrhagic shock Hypovolemic shock is a form of shock caused by severe hypovolemia (insufficient blood volume or extracellular fluid in the body). It could be the result of severe dehydration through a variety of mechanisms or blood loss. Hypovolemic shock is a ...

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 may ...

(heart attack), and

stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...

Types

One of the first substances that was reported to produce an oxygen diffusion-enhancing effect was

crocetin Crocetin is a natural apocarotenoid dicarboxylic acid that is found in the crocus flower together with its glycoside, crocin, and '' Gardenia jasminoides'' fruits. It forms brick red crystals with a melting point of 285°C. The chemical struct ...

, a carotenoid that occurs naturally in plants such as ''

crocus sativus ''Crocus sativus'', commonly known as saffron crocus or autumn crocus, is a species of flowering plant in the iris family (biology), family Iridaceae. A cormous autumn-flowering cultivated perennial plant, perennial, unknown in the wild, it is ...

'', 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 and styles, called threads, are collected and dried for use mainly as a seasoning and colouring agent i ...

. Saffron has been used culturally (e.g., as a dye) and medicinally since ancient times.

Trans sodium crocetinate Crocetin is a natural apocarotenoid dicarboxylic acid that is found in the crocus flower together with its glycoside, crocin, and '' Gardenia jasminoides'' fruits. It forms brick red crystals with a melting point of 285°C. The chemical structur ...

(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 Glioblastoma, previously known as glioblastoma multiforme (GBM), is one of the most aggressive types of cancer that begin within the brain. Initially, signs and symptoms of glioblastoma are nonspecific. They may include headaches, personality ch ...

, an aggressive form of brain cancer. TSC, which is being developed by

Diffusion Pharmaceuticals Diffusion Pharmaceuticals Inc ( NASDAQ:DFFN) is a publicly traded biotechnology and drug development company based in Charlottesville, Virginia, U.S. It was co-founded in 2001 by American life sciences entrepreneur David Kalergis and University ...

, 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.

is currently investigating the use of

trans sodium crocetinate Crocetin is a natural apocarotenoid dicarboxylic acid that is found in the crocus flower together with its glycoside, crocin, and '' Gardenia jasminoides'' fruits. It forms brick red crystals with a melting point of 285°C. The chemical structur ...

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 COVID-19 pandemic in Hubei, identified in Wuhan, China, in December ...

, acute

, 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 b ...

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, th ...

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 a ...

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

{{reflist Oxygen Diffusion Chemical compounds Biochemistry Drugs by mechanism of action