[Influence of partial hepatectomie on ammoniumdetoxications function of liver at chronic tetrachlorcarbon hepatitis].

The purpose. To study the effect of partial hepatectomy (PH) on the main ways of ammonia detoxication in the liver (synthesis of urea and glutamine) in chronic tetrachlorcarbon (CCl4) hepatitis. Methods. The experiments were performed on 165 white outbred rats (females) weighing 180-220 g Chronic CCl4-hepatitis was reproduced by subcutaneous injection of 50% CCl4 solution in olive oil (0.1 ml/100g of body weight,65 days, through the day with two two-week breaks between 6-7 and 13-14 injections). PH conducted electrocautery, removing part of the left lobe of the liver (15-20% by weight of the body) to 65th (and last) day of the introduction of the CCl4. Animals were studied after 65 days of development of CCl4-hepatitis on day 3, 7 and 14 days after laparotomy («falsely operated¼ animals) and partial hepatectomy. In subcellular fractions of the liver investigated the activity of phosphatdependent glutaminase (FDG), glutamatdehydrogenaze (GDG), glutaminsintetaze (GS), arginase. In the liver tissue investigated the content of ammonia, glutamine, glutamate and urea. Results. Found that on 65-th day of the development of CCl4 in the liver decreases the concentration of ammonia, glutamine, glutamate, urea, and activity of GS, GDG and arginase. Activity FDG was not changed. The use of PH on the background of chronic CCl4-hepatitis has a short-term (3 days) a stimulating effect on the activity FDG, GS, postponed (14 days) the inhibitory effect on the activity of GDG. This was accompanied by an increase in the concentration in the liver of ammonia within 14 days of the postoperative period on the background of maintaining reduced concentrations of glutamine and glutamate it. The stimulatory effect of CHA on the activity of arginase is saved to the 14th day of the postoperative period, however, the concentration of urea in the liver remained below normal. Conclusions. The obtained results show that CGA on the background of chronic hepatitis increases the pathological impact of CCl4 on amniocentesis liver function.

[Urea formation in the after operational liver].

The effect of resection of the left lobe of the liver (LR, 15-20% og the organ weight) on hepatic urea formation was investigated in 84 albino rats. The objects of study were the surgery left (LLP), inoperable middle (MLP) lobe of the liver, blood (aorta, v. hepatica, v. porta) and choledochal bile. They studied the urea content. Arginase activity was examined in liver homogenate. On the day 3 and day 7 after resection reduced arginase activity was detected. LR caused a decrease of urea in v. hepatica, but increased urea content in the arterial blood and v. porta. Increase in bile urea on day 7 it was replaced by a decrease observed on day 14 of the postsurgery period. The concentration of urea in the liver on the 3rd day after LR was below the norm, and on the 7th and 14th day was within it. The results indicate a violation of urea operated by hepatocytes of the liver and extrahepatic activation mechanisms of the formation of urea.

Effect of Liver Damage and Hyperbaric Oxygenation on Glutamine Synthetase of Hepatocytes.

Activity of glutamine synthetase in the hepatocytes of healthy animals and animals with chronic CCl4-induced hepatitis was studied on white mature female rats after liver resection (15-20% of organ weight) and hyperbaric oxygenation (3 atm, 50 min, 3 times). Surgically operated left and non-operated middle lobes of the liver were analyzed on day 3 after liver resection and exposure to hyperbaric oxygenation. On day 65 of CCl4 poisoning, activity of glutamine synthetase decreased in both lobes and did not recover on day 3 after toxin cessation. Liver resection under conditions of CCl4-induced hepatitis restored reduced activity of glutamine synthetase in both liver lobes to the normal level. In healthy rats, the increase in glutamine synthetase activity after liver resection was found only in the middle lobe of the liver. Hyperbaric oxygenation enhanced the stimulatory effect of liver resection on glutamine synthetase activity in hepatocytes during chronic CCl4-induced hepatitis. In healthy animals with liver resection, activity of glutamine synthetase did not change after hyperbaric oxygenation, while normally oxygenation inhibited glutamine synthetase activity.

[Kinetics of nitrogenous metabolites in the kidney during chronic tetrachloromethane hepatitis].

The kinetics of ammonia, glutamine, and urea in the kidney has been studied in experiments on 203 white rats (females) at the end of chronic tetrachloromethane (CCl4) exposure (65 days) and within 14 days after cessation of CCl4. It was found that on the 65th day of CCl4 administration the arterial hyperammoniemia is formed, which lasts for 14 days after the abolition of the toxin. This is accompanied by an increased excretion of ammonia in the urine and an increase in its concentration in the blood of renal veins, which does not prevent its accumulation in renal tissue. In chronic CCl4-hepatitis model are the changes of glutamine concentration in arterial blood are developing by type of hypo- and hyperglutaminemia. CCl4 stimulates accumulation of glutamine by the kidneys at the end of exposure and at early stage of the recovery period. Toxin cessation activates processes which are stabilizing the normal concentration of glutamine in the kidney by changing glutamine incretion from kidney to renal blood flow. Long-lasting CCl4 exposure increases the concentration of urea in the arterial blood and its urinary excretion. Simultaneously urea reabsorption is activated in the kidneys, which contributes to an increase in its concentration in the blood of the renal veins.

[Effect of hyperbaric oxygenation on metabolism of glutamine in the liver].

The effect of three-day course of hyperbaric oxygenation (HBO; 3 atm, 50 min, 1 session per day) on glutamine metabolism in the liver has been investigated in 72 adult albino rats. The content of ammonia, glutamate, glutamine, activity of glutamine synthetase (GS), phosphate-dependent glutaminase (PDG), and glutamate dehydrogenase (GDH) were studied in left (LLL) and median (MLL) lobes of the liver. The course of HBO had an inhibitory effect on all the enzymes studied. Inhibitory effect of hyperoxia on GDH activity persisted up to day 11 after the course of HBO in both lobes of the liver, while decreased glutamate normalized in both lobes. Reduced glutamine concentration normalized to day 4, and the concentration of ammonia and remained elevated for 11 days after the end of hyperoxic exposure. Inhibitory effect of hyperoxia on GS activity in LLL and MLL disappeared on day 4 and day 11 day after the end of the HBO course. PDG activity reduced by HBO in both lobes normalized to the day 4 day after oxygenation; however, on day 11 it selectively decreased in LLL, where simultaneous stimulation of GS activity was also observed. The results demonstrate different sensitivity of liver GS, PDG and GDH of normal rats to the inhibitory effect of HBO. Different dynamics of GS and PDG activity in LLL and MLL of oxygenated rats suggests functional heterogeneity of the glutamine cycle in hepatocytes of liver lobes after HBO.

Phosphate-dependent glutaminase response to liver injury and hyperbaric oxygenation.

Activity of phosphate-dependent glutaminase was determined in hepatocytes of white female rats, both in healthy animals and in rats with chronic CCl4-hepatitis on day 3 after liver resection and hyperbaric oxygenation. In healthy animals, activity of phosphate-dependent glutaminase was not altered after hepatic resection, but it was elevated in animals with chronic CCl4-hepatitis. Hyperbaric oxygenation inhibited activity of hepatocytic phosphate-dependent glutaminase in non-operated healthy rats but stimulated it after hepatic resection. In animals with chronic CCl4-hepatitis; hyperbaric oxygenation restricted the stimulating effect of hepatic resection on phosphate-dependent glutaminase activity.

[Correction of glutamine metabolism impairments in the operated liver with chronic hepatitis by hyperbaric oxygen].

Application of hyperbaric oxygenation (HBO, 3 ata, 1 session for 50 min per day) during the first three days after liver resection (LR, 15-20% from the organ mass) in animals with chronic toxic hepatitis (CCl4, 50%, 0,1 ml/per 100 g of body mass, subcutaneously, once in 2 days, 65 days) eliminates a deficit of glutamine and glutamate in an operated liver and prevents accumulation of the endogenic toxin, ammonia, caused by combined effects of CCl4 and LR. Thus hyperbaric oxygen modulates the effect of the LR on the activity of key enzymes of the glutamine metabolism in liver: glutamine synthetases (GS) and phosphate-dependent glutaminases (PDG). HBO enhanced and prolonged the LR effect of the GS activity and restricted analogous changes in PDG during an early (3 day) postoperative period and promoted a delayed transient stimulation in the late (7 day) postoperative period. In contrast to non-oxygenated animals with LR this was not accompanied by accumulation of ammonia and the decrease in glutamine concentration in the liver.

[Impact of hyperbaric oxygenation on nitric balance of gastrointestinal organs at hepatectomy: experimental study].

The study was undertaken to examine nitrogen metabolism in gastrointenstinal tract tissues in endogenous ammonia intoxication caused by liver resection (LR) and the impact of three-day hyperbaric oxygenation (HBO) on the metabolism. The albino rat samples of arterial (aortic) and venous (portal) blood and the tissues of the stomach, duodenum, and large bowel were the subject of this investigation. HBO was made thrice at 3 ata as a 50-min session within the first three days after LR (15-20% of the mass of the organ). The levels of ammonia, glutamine, and urea were measured. HBO prevents postoperative arterial hyperammonemia, the gastrointestinal accumulation of ammonia, by reducing its accumulation in the portal blood. HBO stimulates the development of LR-caused portal hyperglutaminemia and the decrease of GIT tissue uptake of "arterial" glutamine and regulates the influence of an operation on the levels of this metabolite in GIT tissues. HBO elevates the content of urea in the arterial and portal blood, without affecting the LR-induced change in its GIT tissue concentration. Hyperbaric oxygen regulates adaptive GIT tissue nitrogen metabolic reactions caused in response to liver resection.

[Effect of hyperbaric oxygenation on glutamine metabolism in damaged and intact lobes of the operated liver]. / Vliianie giperbaricheskoi oksigenatsii na metabolizm glutamina v povrezhdennoi i nepovrezhdennoi doliakh operirovannoi pecheni.

Employment of hyperbaric oxygenation (HBO, 3 bar, 50 min, 1 session per day) during the first three days after resection of liver (15-20% of mass) normalized glutamine metabolism impairments caused by operational trauma.

[The ammonia neutralization function of the liver in chronic active hepatitis]. / Sostoianie ammiakobezvrezhivaiushchei funktsii pecheni pri khronicheskom aktivnom gepatite.

In experiments on 182 white male rats hepatitis was modelled by percutaneous injection of 0.1 ml/500 g of tetrachloromethane (TCM) dissolved in olive oil. TCM was injected every other day for 65 days. After development of hepatitis (in 65 days) synthesis of glutamine and urea, partial oxygen pressure in the liver were studied. It is shown that modelling of chronic hepatitis leads to impairment of glutamine and urea synthesis, reduction of tissue blood flow and oxygen partial pressure. It is suggested that the reason of these changes is inhibition activity of glutamate dehydrogenase, arginase and short-term depression activity of phosphate-dependent glutaminase. The changes in the enzymatic activity lead to lowering tissue level of glutamine, urea, accumulation of ammonia ions. These changes persist for 14 days after the last injection of tetrachloromethane.

[Glutamine metabolism in the liver after partial hepatectomy in chronic hepatitis]. / Metabolizm glutamina v pecheni posle chastichnoi gepatéktomii na fone khronicheskogo gepatita.

A long-term treatment of female rats with CCl4 caused a decrease of glutamine content in the liver. This decrease may be attributed to stable reduction of glutamine synthetase activity and slightly elevated (or unchanged) phosphate-dependent glutaminase. Partial hepatectony (15-20% of the liver) did not normalise glutamine metabolism.

[Glutamine metabolism in the brain and in the liver in critical conditions]. / Osobennosti metabolizma glutamina v golovnom mozge i pecheni pri kriticheskykh sostoianiiakh

Experiments on cats and rats have established that critical conditions caused by acute hemorrhage, hepatotoxin, and hepatectomy lead to ammonia accumulation in the brain and liver due to the predominance of decay of glutamine over its formation in these organs. With this, the depressed formation of glutamine is a universal cell response to a pathogenic agent whereas a change in glutamine deamination in disease depends on both the nature of a pathogenic agent and the organ wherein this reaction occurs.

[Ammonia-neutralizing function of hepatocytes after experimental liver resection]. / Sostoianie ammiakoobezvrezhivaiushchei funktsii gepatotsitov posle rezektsii pecheni v éksperimente.

The experimental study has established that a 15-20% resection of a hepatic mass in healthy rats inhibits glutamine formation in hepatocytes and stimulates its decomposition in liver cells promoting ammonia accumulation in the operated liver. The hepatocyte urea synthetizing cycle can not prevent accumulation of ammonia in the liver and raise their urea content even if arginase activity is high. Inhibition of GDG activity in the operated liver not only limits formation of ammonia during glutamate deamination but also results in glutamine deamination inhibition in hepatocytes. These disorders of hepatocytic ammonia neutralizing function persist for 21 days after hepatic resection.

[Glutamine metabolism in damaged and intact lobes of the operated liver]. / Osobennosti metabolizma glutamina v povrezhdennoi i nepovrezhdennoi doliakh operirovannoi pecheni.

The experiments have shown that even resection of relatively small (15-20%) portion of the intact liver resulted in significant changes of glutamine metabolism in hepatocytes, which were not eliminated for 21 days of postoperative period. The changes of the activity of key enzymes of glutamine metabolism, glutamine synthetase and glutaminase (phosphate-dependent), are responsible for these alterations. The changes of activity of these enzymes closely depend on the location of hepatocytes to focus of mechanical damage.

[The hyperbaric oxygen therapy of disordered ammonia detoxication in the operated liver]. / Giperbaricheskaia kislorodnaia terapiia narusheniia obezvrezhivaniia ammiaka v operirovannoi pecheni.

The status of the main routes of ammonium detoxication in the liver (synthesis of glutamine and urea) after its resection and hyperbaric oxygenation (HBO) was studied in 160 rats. HBO (3 sessions at 3 atm. abs.--50 min) following resection of the liver stimulated the activity of glutamine synthase and prevented the reduction of glutamate (a substrate for glutamine synthesis) level in the operated on liver. Hyperbaric oxygen activated the glutamine-dependent and non-glutamine-dependent pathways of urea synthesis in the resected liver and ensured the incorporation of glutamine amido groups in the ornithine cycle. HBO boosted the inhibitory effect of liver resection on the activity of glutamate dehydrogenase and prevented the accumulation of ammonium in the hepatocytes of resected liver. The stimulating effect of HBO on the ammonium-detoxifying function of the resected liver persisted for 11 days after the exposure.

[Role of hyperbaric oxygenation in the mechanism of ammonium detoxication in resection of the liver in the presence of chronic hepatitis]. / Rol' giperbaricheskoi oksigenatsii v mekhanizme detoksikatsii ammiaka pri rezektsii pecheni na fone khronicheskogo gepatita.

Hyperbaric oxygenation (HBO) used in 170 white rats with chronic CCL4-hepatitis after resection of the liver was conducive to repair of the reversible (glutamine synthesis) and irreversible (urea synthesis) routes of ammonium binding in hepatocytes which are disordered in chronic hepatitis. Hyperbaric oxygen regulates the effect of resection of the liver on the glutamine- and urea-synthesizing function of the hepatocytes in chronic hepatitis. Therapeutic effect of HBO persists for 4 days of the posthypoxic period under conditions of posthyperoxic hypoxia.