Hyaluronic acid against cirrhosis and other liver diseases
Save the liverL.A.Trusov, "Nanometer"
In addition to fools and roads, there is another widespread problem in Russia, which often leads to cirrhosis or liver fibrosis.
Special stellate cells are responsible for the process of liver degeneration, which produce a large amount of extracellular matrix in response to harmful effects, replacing dead hepatocytes with connective tissue. Attempts at liver antifibrosis therapy are mainly aimed at these cells. And in order to ensure the stability of the drug agent in the body, such methods as, for example, modification with polyethylene glycol (PEG) are used.
Although PEG is a seemingly biocompatible agent, however, it is still a compound foreign to the body. A group of Korean researchers suggests using another compound for these purposes – hyaluronic acid. (About the wonderful properties of hyaluronic acid, which gives our skin firmness and elasticity, see the articles "You can rejuvenate the skin – you just need to know how" and "Giamatrix – almost living skin" – VM.) The cells of the lymphatic system, liver, kidneys have special hyaluronic receptors that recognize hyaluronic acid. And if there are receptors, it means that liver cells are able to accumulate medications modified with hyaluronic acid.
As a model therapeutic agent, scientists used a derivative of hyaluronic acid, to which quantum dots were additionally attached to visualize the accumulation process in cells (what turned out was called HA-Qdot). In vitro experiments revealed that both healthy liver cells, stellate cells, and liver cancer cells accumulate HA-Qdot, and stellate and cancerous cells do this more intensively (Figure 1).
Confocal microscopy of HA-Qdot-treated cells.
FL83B - normal hepatocytes;
HSC-T6 - Stellate liver cells;
HepG2 - hepatoma cells.
In vivo experiments used mice in which cirrhosis of the liver was caused by repeated injections of CCl 4.
(Carbon tetrachloride has a narcotic effect, affects the central nervous system, causes severe dystrophic changes in the liver, kidneys, heart and other organs. The lethal dose of CCl 4 for humans is 30-60 ml – VM.)
Figure 2 shows that the liver of animals has indeed undergone changes.
The appearance of a normal mouse liver
and liver after eight weeks of CCl 4 treatment.
Then, both healthy mice and mice suffering from cirrhosis were injected with the same doses of HA-Qdot into the tail vein, and then the distribution of quantum dots in the animals' bodies was monitored in real time. It turned out that initially quantum dots accumulate in the liver in both of them, but in healthy mice they are completely eliminated from the body in a few days, while in patients they remain localized in the liver (Figure 3).
Accumulation of the drug in the mouse body:
(a) a healthy mouse; (b) a mouse suffering from cirrhosis.
Researchers explain this phenomenon by the fact that the damaged liver is not able to effectively dispose of accumulated substances. From the point of view of therapy, this is even good – the medicine is longer exactly where it is needed.
At the same time, the drug did not accumulate in significant amounts in other organs of the mouse – in the lungs, in the kidneys (Figure 4).
Distribution of HA-Qdot in the liver, lungs and kidneys
3 days after injection into the caudal vein.
Left: a healthy mouse; right: a mouse with cirrhosis.
Thus, drugs modified with hyaluronic acid can selectively accumulate in the damaged liver and, therefore, be used for long-term therapy of chronic hepatitis, cirrhosis of the liver and its malignant neoplasms. The work "Bioimaging for Targeted Delivery of Hyaluronic Acid Derivatives to the Livers in Cirrhotic Mice Using Quantum Dots" is published in the journal ACS Nano.
Portal "Eternal youth" http://vechnayamolodost.ru23.06.2010