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Polyprenols and neurotransmitter systems in the brain (preclinical studies)

Preclinical study.

The study was conducted in laboratory conditions. It is known that when hepatic encephalopathy occurs, not only liver cells but also brain cells are damaged. The study examined the activity of different parts of the brain in rats with experimental hepatic encephalopathy after the introduction of the polyprenolic preparation.

It turned out that polyprenols have marked protective properties, eliminating the devastating effects of toxins on the brain. The main conclusion of the study is the potential of use of polyprenols for the treatment and prevention of acute hepatic encephalopathy as well as other diseases associated with damage to the mitochondria and mitochondrial dysfunctions in the body.

Solagran Limited, Melbourne, Australia
S.M. Kirov Academy of Forestry Engineering in Saint Petersburg, Saint-Petersburg, Russia
I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, Saint-Petersburg, Russia

Introduction

On the experimental model of hepatic encephalopathy (HE) caused by toxic action of carbon tetrachloride (CCL1), destruction of membranes not only of liver cells but also a disorder of neurotransmission in the brain takes place. The toxicant leads to the generation of membrane-aggressive metabolites with the subsequent activation of processes of lipid peroxidation of membranes of hepatocytes and mitochondria in the brain. The search for preparations of directed action, especially those of vegetable origin, makes it possible to protect the brain and liver and prevent the development of pathologies.

Study Purpose

Analysis of the action of the polyprenolic preparation (PP) made of conifer needles and the nootropic action preparation of gliatilin in preventing the development of experimental hepatic encephalopathy in rats at early stages of development of a pathology on the basis of dynamics of activity of enzymes of acetylcholinesterase (ACHE), butyrylcholinesterase (BuChE), monoamine oxidase (MAO) in different structures of the brain.

Methods

The activity of ACHE was measured by the Ellman method in the homogenates of hypothalamus, striatum and medulla oblongata, the activity of BuChE was measured in the blood serum. The activity of MAO was determined by the spectrophotometric method of Lowry with the substrate of serotonin-creatinine sulfate in the homogenates of the brain. The work was performed in 84 male rats of the Wistar line. Acute toxic hepatitis and HE was induced in the animals by introducing CCI4 in the dose of 0.2 ml 100 g subcutaneously for 4 days. Starting with the 2nd day of the experiment, the studied medications were administered orally in the dose of 60 mgkg of weight within 7 days.

Results

The introduction of CCI4 to rats was accompanied by the multidirectional variation of activity of ACHE in all the studied divisions of the brain. The detected changes depended on the division of the brain and on the duration of exposure to CCU. The consequences of toxic effect of CCI4 were eliminated to different extents under the influence of the studied medications. In hypothalamus and striatum, PP showed protective action at an early stage, and in the hypothalamus it turned out to be a pronounced inhibitor of activity of ACHE after 7 days of administration. The introduction of CCL1 reduced the activity of BuChE in the blood serum in rats, which was associated with the development of toxic hepatitis and HE. The studied medications equally reduced the negative impact of CCL1, manifesting a hepatoprotective effect. A disorder of monoaminergic transmission, that was associated with the reduction of MAO activity in all the studied divisions of the brain was also observed under the influence of CCU. It was found that the studied medications have no effect on the rate of reaction of deamination of serotonin in all the studied divisions of the brain on the 3rd, 5th and 7th days of use of the medications, whereas previously we have shown the effectiveness of these medications by the 21st day of application.

Conclusion

Thus, PP at the early stages of HE showed a stronger protective effect on the cholinergic system of transmission of nervous impulse in the striatum and medulla oblongata compared to gliatilin, which indicates that the use of this medication is promising for the treatment and prevention of this pathology and, apparently, other diseases associated with the damage to the mitochondria and mitochondrial dysfunctions in the body. (Published in the proceedings of the 2nd Conference of the Russian Association of Psychoneuroendocrinology (RAPNE), Moscow, 2010)


The text of the study is provided by courtesy of Solagran.