Experimental Liver Damage Research Articles

Action of streptokinase on parameters of hemostasis in rabbits with toxic liver damage due to carbon tetrachloride

The authors study the specific nature of changes in the parameters of hemostasis in rabbits with experimental toxic liver damage. Streptokinase was injected intravenously. Toxic liver damage was induced by injections of carbon tetrachloride. The parameters studied included acceleration of lysis of the blood clot, increased fibrinolytic activity and thrombin time, lowered level of fibrinogen and antithrombin III.

Effectiveness of colchicine in experimental alcohol-induced liver damage

Effectiveness of colchicine in experimental alcohol-induced liver damage

Changes in activation of aspartate aminotransferase by pyridoxal 5'-phosphate after experimental liver damage in rabbits

The aspartate aminotransferase activity with and without pyridoxal 5'-phosphate supplementation was examined in mitochondrial and cytoplasmic preparations from fresh human heart and liver samples. The apoenzyme was fully saturated in all cases. Liver cell damage was produced by ischaemia and carbon tetrachloride poisoning in two groups of rabbits. The activity of aspartate aminotransferase with and without pyridoxal 5'-phosphate was measured in the plasma and in cytoplasmic and mitochondrial preparations from both groups. After carbon tetrachloride poisoning the enzyme activity in the plasma increased within 2 h but was not enhanced by pyridoxal 5'-phosphate. Following ischaemia, plasma enzyme activity only increased between 4 and 8 h and was progressively stimulated by pyridoxal 5'-phosphate. Up to 15 h after carbon tetrachloride poisoning the liver cytoplasmic and mitochondrial apo-enzyme remained fully saturated with co-enzyme. In contrast, a pronounced loss of co-enzyme occurred in both fractions of the ischaemic group. These results suggest that the type of injury and not necessarily the organ affected could determine the degree of activation of aspartate aminotransferase by pyridoxal 5'-phosphate observed in human myocardial infarction and liver disease.

Active principles of crude drugs on experimental liver damage: Results of screening test and the activity of essential oil of crude drugs

Active principles of crude drugs on experimental liver damage: Results of screening test and the activity of essential oil of crude drugs

In vivo und in vitro Hydroxylierung von Androgenen in Ratten nach Leberschädigung und Nahrungskarenz / In vivo and in vitro hydroxylation of testosterone and dihydrotestosterone in rats after liver damage and starvation

The in vivo C-2-hydroxylation of testosterone and 5-dihydrotestosterone in rats was measured by labilisation of tritium as HTO after injection of [1 alpha, 2 alpha-T]testosterone or [1 alpha, 2 alpha-T]5 alpha-dihydrotestosterone (radiospirometry). After experimental liver damage caused by CCl4 or after starvation for 60 h the hydroxylation of the androgens decreased. Similar results were gained by measuring the C-2-hydroxylation of testosterone, 5 alpha-dihydrotestosterone and estradiol.

Biochemical changes in the myocardium after experimental liver damage

Biochemical changes in the myocardium after experimental liver damage

An automated continuous-flow assay for serum sorbitol dehydrogenase activity and its use in experimental liver damage

An automated continuous-flow assay to monitor sorbitol dehydrogenase activity (EC 1.1.1.14) in serum has been developed. The amount of serum required is 240 μl and 50 samples can be analyzed per hour. The method features an automatic blank substraction and a linear range from 0 to 500 mU/ml. In order to validate the method, sera from control rats and rats preexposed to carbon tetrachloride were analyzed and compared to results obtained using a manual reaction-rate assay. The resulting correlation coefficient was 0.99.

Correlation between serum lecithin-cholesterol-acyltransferase activity and erythrocyte lipid content during experimental liver damage.

Intravenous injection of 10 mg/kg praseodymium nitrate into female Wistar rats causes a severe liver damage manifested by liver cell necroses, hepatic fat infiltration and disturbances of serum lipid metabolism. Analysis of serum lipoprotein lipid content showed a contrasting behaviour of the low and the high density lipoproteins. Unesterified cholesterol and phosphatidylcholine contents of the low density lipoproteins were slightly decreased 24 h after praseodymium, followed by an 8-fold increase after 96 h. A pronounced diminution of unesterified cholesterol and phosphatidylcholine contents in the high density lipoproteins within 24 h returned to control values after 96 h.

Application of nicotinamide-adenine dinucleotide analogs for clinical enzymology: alcohol dehydrogenase activity in liver injury

The activities of alcohol dehydrogease(ADH) in serum and in the subcellular fractions of rat liver were determined with n-amyl alcohol or ethanol as substrate and thionicotinamide-adenine dinucleotide as coenzyme. It was found that the enzymes's activity ratio on the amyl alcohol and ethanol(A/E value) of serum and on the particulate fractions of the liver were different, but the A/E value of the soluble fraction was similar to that of serum. The A/E value of the particulate fractions were higher than that of the soluble fraction. From the results of experimental liver damage in the rat, it seems that estimation of the A/E value of ADH activity in serum is a useful parameter for the diagnosis of active liver injury. Since the A/E values of patients' sera differed from those of the normal subjects, the estimation of the A/E value of serum may give diagnostic information on liver injury, especially in chronic liver injury.

Protective action of dithiocarbamates on experimental liver damage produced by carbon tetrachloride

The protective action of dithiocarbamates on CCl 4-induced liver damage in rats was assessed with liver function tests (BSP retention test and SGPT). When given immediately before CCl 4, all dithiocarbamates tested showed a protection against CCl 4 hepatotoxicity except for zineb and some “polymer” dithiocarbamates. For zineb it appears plausible that this was caused by a delayed absorption. No protection was found when one of the dithiocarbamates studied was given 1 hr after CCl 4 administration. From studies with some metabolites and related compounds it appears that only substances containing a carbon disulphide group have a protective action. Probably these compounds function as effective free radical scavengers. In addition, inhibition of microsomal liver enzyme activity and a lowering of body temperature could also be contributing factors.

Lactatc Dehydrogenase Isoenzymes in Normal BovineSerum and during Experimental Liver and Muscle Damage

Lactate dehydrogenase (LDH) isoenzymes were determined in normal bovine serum and at different time intervals in sera from cattle with experimental liver and muscle damage. The fast-moving isoenzyme LDH1, increased in two phases during liver necrosis. The first phase appeared to be related to the liver damage, while a further increase was likely to be due to a general intoxication. LDH1 also increased after a period of 7 to 9 days’ starvation, possibly due to changes in the liver. The slow-moving isoenzyme LDH5 appeared to be largely muscle specific and the rise of its activity in serum appeared to bear some relationship to the extent ofthe muscle damage.

Arginase activity, arginine and ornithine of plasma in experimental liver damage.

In the acute phase of CCl(4) poisoning of the rat, we observe a marked increase of arginase activity in the plasma, a contemporaneous significant increase of ornithine, and the disappearance of arginine. Experiments carried out in vivo and in vitro show that the changes in plasma concentration of arginine and ornithine are related to the increase of plasma arginase activity. In the experimental necrotic-type liver damage studied, arginase - even on the plasma level - carries out its activity of transforming arginine into ornithine and urea.

Serum Xanthine Oxidase and Liver Disease

A recently-described assay for xanthine oxidase was used for the estimation of serum xanthine oxidase (SXO) in patients with a variety of liver disorders. SXO was markedly increased in acute viral hepatitis, and in some patients with chronic aggressive hepatitis. In other forms of chronic liver disease or obstructive jaundice, there was little or no increase of this enzyme in serum. The results of a study of experimental liver damage in rats suggest that SXO is more sensitive than serum aminotransferases in detecting acute liver damage.

Inactivation of gastrin-like synthetic peptide by the liver and serum, and its clinical significance.

Using the method of gastrin bioassay and its modified technique, the inactivation of gastrin-like synthetic peptide was found to exist both in the liver and serum. The experimental liver damage induced by carbon tetrachloride (CCl4) reduced the gastrin-like peptideinactivation in the liver. These findings may indicate that the high incidence of peptic ulcer among the patients with liver diseases is due in part to hypergastrinemia caused by a disturbed inactivation of endogenous gastrin in the liver.

On the protective action of zinc against experimental liver damage due to choline free diet or carbon tetrachloride.

Parenterally administered zinc chloride inhibited fatty infiltration in the liver of rats which had been fed a choline free diet.

Comparative studies on got isozyme of liver tissue in experimental liver damage in rat and infantile jaundice

Comparative studies on got isozyme of liver tissue in experimental liver damage in rat and infantile jaundice

Studies on Plasma Angiotensinases in Liver Disease

1. Plasma angiotensinase activity was significantly increased in patients with various kinds of liver diseases. The patterns of angiotensinase activity in plasma from normal subjects and patients with liver diseases were compared by horizontal starch block electrophoresis. Angiotensinase activity in normal plasma was found only in the albumin zone, while in plasma from patients with liver diseases it was found not only in the albumin zone but also in the γ-globulin zone. On recovery of the patient, angiotensinase activity in the γ-globulin zone was not demonstrated. This angiotensinase, which was demonstrated electrophoretically in the γ-globulin zone, was named angiotensinase G. 2. On experimental liver damage in rabbits, the findings obtained in human beings were confirmed. 3. Angiotensinase G inactivated both α-asp1-val5-angiotensin II and (α-asp1(NH2)-val5-angiotensin II, but did not inactivate β-asp1 val5-angiotensin II. The optimal pH of the enzyme was between 6.8 and 7.1. The activity of the enzyme was completely inactivated by ethylenediaminetetraacetate treatment and the full activity was restored by addition of manganese. Its activity was inhibited by trasylol as well as diisopropylfluorophosphate. 4. Angiotensinase G could not be detected either in liver extract from normal rabbits or from rabbits with experimental liver damage. When normal rabbit plasma was incubated together with liver extract, angiotensinase G was demonstrated electrophoretically in the incubation mixture. In vitro experiments indicated that γ- or β-globulin fraction of plasma and a heat unstable and non-dialyzable substance in microsome fraction of liver cells were essential for the formation of angiotensinase G. 5. The appearance of angiotensinase G seemed to be one of the factors of an increase of plasma angiotensinase activity in liver diseases. The possible role of an increase of plasma angiotensinase activity on the contribution to the blood pressure reduction in liver diseases was discussed.

Evaluation of phenyl acetate esterase activity as an index of liver damage

Phenyl acetate esterase, which is an A- or arylesterase according to Augustinsson's classification, was studied in serum and liver of mice, and in human serum. The following results were obtained. 1. 1. On subcellular fractionation, highest activity was found in the microsomal fraction, and migrated with the same mobility as serum albumin on starch block electrophoresis. 2. 2. Phenyl acetate esterase activity in mouse liver was used for the evaluation of drugs against liver injuries. 3. 3. Experimental liver damage was shown to be accompanied by a decrease of the phenyl acetate esterase activity in liver and serum simultaneously. 4. 4. The highest peak of activity in serum was found in the region of the albumin or prealbumin on starch block electrophoresis; it decreased in experimental liver damage in mice, or in cirrhosis in man. 5. 5. The marked decrease of phenyl acetate esterase activity in serum suggested with high probability the diagnosis of liver cirrhosis, or severe liver damage.

Plasma angiotensinase activity in liver disease

The electrophoretic detection of the appearance of plasma angiotensinase activity in the γ-globulin zone, named angiotensinase G, in patients with liver damage was studied using rabbits. Angiotensinase G could not be detected either in liver extract from normal rabbits or from rabbits with experimental liver damage. When normal rabbit plasma was incubated together with liver extract, angiotensinase G activity was demonstrated electrophoretically in the incubation mixture. In vitro experiments indicated that γ- or β- globulin fractions of plasma and a heat unstable substance in microsome fractions of liver cells were essential for the formation of angiotensinase G.

Clearance of exogenous histamine from blood of rats with experimental liver damage.

Liver plays a primary role in the metabolism and degradation of endogenous histamine. Hepatocellular damage may be associated with increased histaminemia due to the deficiency of hepatic clearance of portal blood histamine (DRAPANS el al., 1965). We assumed that liver also contributes to the degradalion of exogenous histamine and that this degradation becomes deficient in the presence of hepatic injury. Such an injury was produced in rats with ethionine. Clearance of exogenous histamine from circulation was then studied in normal and ethioninetreated an im a 1 s .