[Effect of the lysosomotropic preparation suramin on the ultrastructural and functional characteristics of rat liver cells in acute toxic hepatitis]. / Vliianie lizosomotropnogo preparata suramina na ul'trastrukturnye i funktsional'nye osobennosti kletok pecheni krys pri ostrom toksicheskom gepatite.

A study was made of the influence of suramin and of a combination of suramin and CCl4 on the ultrastructure of hepatocytes, structural and functional state of lysosomes and functional activity of the rat's liver. The latter was characterized by alanine aminotransferase level in blood. Increasing amounts of autophagosomes as well as lysosomal fusion disturbances were registered 24 and 48 hours after a single suramin administration. The combined suramin and CCl4 administration resulted even in a higher damage of hepatocytes. A decrease in the intralysosomal rate of proteolysis in hepatocytes, was also shown in addition to the impairment of liver functional activity. Some ultrastructural features of compensation of the insufficiency of the hepatocyte vacuolar apparatus were noted during suramin and CCl4 administration. Changes in the nucleolar structure were noticed in hepatocytes administered both suramin and CCl4. It is suggested that these changes may involve a compensatory increase in nucleologenesis due to the decrease in the activity of the protein-synthesizing apparatus in hepatocytes.

[Facilitation of the structural and functional disorders of liver lysosomes in toxic hepatitis due to the suppression of intralysosomal proteolysis]. / Usilenie strukturno-funktsional'nykh narushenii lizosom pecheni pri toksicheskom gepatite, vyzvannoe podavleniem vnutrilizosomnogo proteoliza.

Suramin that accumulates in rat liver Kupffer cell lysosomes and inhibits the intralysosomal proteolysis was used to suppress the functional activity of these particles during liver damage (acute CCl4 hepatitis). Polyvinylpyrrolidone that does not disturb protein catabolism in liver lysosomes was employed for reference. According to the characteristic changes in lysosomes induced by suramin (inhibition of acid phosphatase, decrease of the rate of the intralysosomal proteolysis in the liver) and PVP the damaged liver was able to accumulate the lysosomotropic substances under study. Suramin aggravated liver damage and increased the lysosomal labilization, whereas PVP exhibited the protective action. The unfavourable effect of suramin may be linked with the suppression of catabolism of Kupffer cell lysosomes. The data obtained suggest the lack of safety of using the inhibitors of intralysosomal proteolysis in patients with acute hepatitis.

[Dynamics of the structural organization of the liver parenchymal cells in induced autophagocytosis]. / Dinamika strukturnoi organizatsii kletok parenkhimy pecheni myshei v usloviiakh indutsirovannogo autofagotsitoza.

The volume of hepatocytes, their nuclei, cytoplasm, relative and absolute volumes, surface area, number and average volume of cytoplasmic structures have been studied in male mice C57B1 (2-month-old with body mass 19-21 g), 20, 60 min and 72 h after glucagon with glycine buffer in the dose 10 mcg per 100 g of body mass has been injected intraperitoneally. A reverse dependence between glycogen contents and a total volume of cytosegresomes, residual bodies and autophagolysosomes in the hepatic parenchyma is revealed. Acid phosphatase free activity, when hepatic homogenates are treated in 0.25 M and 0.15 M saccharose solutions, is the highest 60 min after glucagon administration. At that time hepatocytes do not contain any glycogen, and volume and number of lysosomes, especially the secondary ones are the greatest. Meanwhile, the total volume of the autophage structures is 150 times as great as the control one. In 60 min the volume of hepatocytes increases nearly by 50%, total volume and number of ultrastructures, especially that of free ribosomes, increase sharply. In 20 min concentration of 11-oxycorticosteroid hormones in blood more than 3 time exceeds the control level. The effect of glucagon dependent on cyclic adenosinmonophosphate is probably realized by means of an enhanced glycogenolysis and an increased level of metabolic processes in the hepatocytes. This causes a deficit of energy substrates, which could, to some extent, be compensated at the expense of reutilization of the lysosomal hydrolysis products.

[Composition of a population of lysosomal structures sedimented during differential centrifugation of mouse liver homogenates]. / Sostav populiatsii lizosomal'nykh struktur, osazhdaemykh pri differentsial'nom tsentrifugirovanii gomogenatov pecheni myshi.

Morphometry was used to measure radiuses and total volumes of lysosomal structures in hepatocytes and sinusoidal cells of male mouse liver. Basing on the data obtained attempts were made to describe possible structural and functional composition and cellular origin of lysosomes in granular functions isolated by differential centrifugation from liver homogenates. The greatest content of hepatocyte lysosomes was found in the group of particles with a radius less than 0.166 micrometer, where, according to the biochemical data, the relative specific activity (RSA) of acid phosphatase was higher as compared with cathepsin D. The fraction of particles with a radius more than 0.490 micrometer was mainly represented by lysosomes and heterophagolysosomes of sinusoidal cells that evidently determines higher RSA of cathepsin D in the fraction as compared with RSA of acid phosphatase.

[Effect of suramin on digestion of 14C-labelled albumin in heterolysosomes of rat liver subcellular fractions]. / Vliianie suramina na rasshcheplenie 14C-mechenogo al'bumina v geterolizosomakh subkletochnykh fraktsii pecheni krys.

The effect of suramin on the state of rat liver lysosomal apparatus 24 and 48 hrs after intraperitoneal injection of the drug was studied. The specific activity of liver acid phosphatase was decreased by suramin down to 35-45% of the control. The inhibitory effect of suramin on the activity of acid phosphatase was observed in all subcellular fractions of the liver and was correlated with the relative content of lysosomal enzymes activity. The sedimentability of lysosomes upon distribution among subcellular fractions was increased. The inhibitory effect of suramin on intralysosomal digestion of 14C-labelled bovine serum albumin was found in nuclear and light mitochondrial fractions, but not in the heavy mitochondrial fraction. The functional heterogeneity of the subpopulations of heterolysosomes and the mechanisms of suramin action on intralysosomal proteolysis are discussed.

Heterophagic function and rate of intralysosomal proteolysis during lysosomotropic agents administration.

Lysosomotropic agents--Triton WR 1339 and suramin--are taken up selectively into lysosomes during in vivo administration and cause specific changes of the particles. Overloading of rat liver lysosomes by Triton WR 1339 was accompanied by the labilization of lysosomes and an increased uptake of [14C]-bovine serum albumin ([14C]-BSA) by the rat liver. The rate of intralysosomal proteolysis was not altered. The capture of 125I-labelled poly(vinylpyrrolidone) (PVP) by the liver was slightly decreased. In the case of suramin administration (250 mg/kg b.w.) the uptake of labelled protein by the liver was not changed. The increased amount of acid-insoluble radioactivity in rat liver was caused by the decrease of intralysosomal protein digestion rate. The lysosomes overloaded by the two kinds of lysosomotropic agents--Triton WR 1339 (with no changes of intralysosomal proteolysis) and suramin (with decreased rate of proteolysis) did not prevent the uptake by liver of substances captured by the adsorptive ([14C]-BSA) or fluid ([125I]-PVP) endocytosis.

[Decrease in the rats of intraliposomal proteolysis and labilization of rat liver lysosomes following suramin administration]. / Snizhenie skorosti vnutrilizosomnogo proteoliza i labilizatsii lizosom pecheni krys pri vvedenii suramina.

Suramin treatment (250 mg/kg bw) 24 and 48 h after administration is followed by the decreased rate of intralysosomal digestion of 14C-bovine albumin. Inhibition of proteolysis and lysosomal overloading with suramin cause the solubilization of acid hydrolases--beta-galactosidase, acid RNase, cathepsin D. There was a significant inhibition of acid phosphatase activity in the rat liver homogenate, suggesting that suramin might be used as a tool to study some features of lysosomal storage disease. Potential mechanisms of the decreased catabolic function of liver ribosomes during administration of lysosomal trophic drugs are discussed.

[Comparison of the effect of acute hypoxia on the rat liver lysosomal apparatus against a background of adaptation to hypoxia and the administration of gutimine]. / Sravnenie vliianiia ostroi gipoksii na lizosomal'nyi apparat pecheni krys na fone adaptatsii k gipoksii i vvedeniia gutimina.

Acute hypobaric hypoxia in rats (260 mm Hg., 90 min) was accompanied by a greater liver lysosomes osmotic susceptibility and by an increase in the relative content of the lysosomal enzymes (acid RNAase and acid phosphatase) in the nuclear fraction. This indicates an enrichment of the liver cell lysosomes with secondary lysosomes. No significant signs of labilization of the liver lysosomes were found. The adaptation of rats to hypoxia, as well as administration of the antihypoxant guthimin or of 1,4-bis-(3'-morpholinopropin-1'-yl-1') benzene hinder these changes to occur in the liver lysosomes during the organism reaction to hypoxia. But the effect of stabilization of the lysosomal membranes in a minor component in the antihypoxia action of the treatment.

[Structuro-functional changes in dog liver and regional lymph node lysosomes in toxic hepatitis]. / Strukturno-funktsional'nye izmeneniia lizosom regionarnykh limfaticheskikh uzlov i pecheni sobak pri toksicheskom gepatite.

Structural and functional changes in the dog liver and regional lymph nodes lysosomes were studied during toxic hepatitis induced by CCl4 administration (single and repeated). Total activity of lysosomal enzymes (acid RNA-ase and beta-galactosidase) was higher in the regional lymph nodes than in the liver, reflecting the barrier, protective function of the organ. During acute toxic hepatitis the specific activities of acid RNA-ase and cathepsin D displayed a sharp rise. No normalization of the indices under study occurred during the observation period (from 8 to 30 days). At the same time there was a rise of the regional lymph node weight and an elevation of the relative macrophage and neutrophil content in the sinuses. The increased activity of the lysosome enzymes in the regional lymph nodes in injury of the liver was connected with greater functional load on the lymph nodes effecting hydrolysis of biopolymeres which penetrated into the regional lymphatic node with the lymph.