Comatose states: etiopathogenesis, experimental studies, treatment of hepatic coma

   


1. Institute of Biomedical Chemistry RAMS
2. Sechenov Moscow Medical Academy
Type: Review
UDK: 612.82, 616.36, 614-08      PubMed Id: 20000119
Year: 2009 vol: 55  issue:4  pages: 380-396
Abstract: The review presents the modern concepts on biochemical mechanisms of processes, that result in comatose states (CS), with emphasis on the search of new therapeutic approaches. CS of various origin causes severe suppression of brain cells functioning and stable unconsciousness. Numerous reasons of various CS are classified into two main groups: primary brain damages (ischemia, tumor, trauma) and secondary damages originating from system injuries in the body (endocrine, toxic e. c.). The most often primary CS is the hypoxic-ischemic one, as result of corresponding encephalopathy. Its mechanism is the brain cells "energy crisis" - because of decreased blood supply or its deficiency by energy substrates or/and by oxygen. Among secondary CS the substantial place takes hepatic coma as a consequence of hepatic encephalopathy in severe liver diseases - cirrhosis, acute liver failure, sharp intoxication. Its main reason is associated with exess of ammonia entering the brain tissue (it accumulates in blood because of lack of its removing by damaged hepatocytes). Ammonia reacts with glutamate in brain astrocytes and the product of this reaction, glutamine, induced osmotic imbalance, that results in change of form and functions of these important brain cells. It induces, in turn, neurons functions damages, changes in neurotransmission and cerebral blood flow and all these may give rise CS. The most of CS studies are carried out in human. Experimental models of hepatic CS are reproduced mainly in rats, the most often by surgery methods. Other models included administration of thioacetamide or D-galactosamine, sometimes in combination with lipopolysaccharide. In earlier studies ammonia administration together with liver damages by ligation or by CCl4 was used. The main principles of hepatic coma treatment include the care of encephalopathy, detoxification, and liver treatment. Elaboration of new nanodrugs with increased penetration into tissues and cells, in particular, on the base of phospholipid nanoparticles, may increase substantially the therapeutic efficiency. One of such drug is thought to be a new hepatoprotective preparation phosphogliv - nanoparticles of soy phosphatidylcholine with glycyrrhizic acid. It is supposed, that the further development of phospholipid nanoforms, with minimal particle sizes, may reveal the more action in CS treatment.
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Reference: Strekalova O.S., Uchaikin V.Ph., Ipatova O.M., Torkhovskaya T.I., Medvedeva N.V., Storozhakov G.I., Archakov A.I., Comatose states: etiopathogenesis, experimental studies, treatment of hepatic coma, Biomeditsinskaya khimiya, 2009, vol: 55(4), 380-396.
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