Glycogen Content Of Hepatocytes Research Articles

Influence of constant lighting on the morphofunctional state and rhythmostasis of the liver of rats

BACKGROUND: There are evidences that light pollution, which causes melatonin deficiency and disruption of circadian rhythm, is associated with the development of malignant neoplasms of the liver, non-alcoholic fatty liver disease, biliary cirrhosis, and a number of other pathologies of this organ.
 AIM: The aim of research was to study the features of chronic influence of constant lighting on lability of morphofunctional state of liver of mature Wistar rats and the structure of circadian rhythms of its parameters.
 MATERIALS AND METHODS: The study was conducted on 80 rats divided into 2 groups: a control group kept under a fixed light regime (light/dark 12/12 h, lights on at 8:00 and off at 20:00), and an experimental group kept under constant lighting 24 h a day. The duration of the experiment was 3 weeks.
 RESULTS: Its established that influence of constant light led to an increase in the size of hepatocytes and a decrease in nuclear-cytoplasmic ratio, average ploidy and proportion of binuclear hepatocytes, and also to development of fatty degeneration, a decrease in the expression of Bmal1 and Clock, and an increase in the expression of per2 and p53 in hepatocytes. At the same time, there was a decrease in glycogen content in hepatocytes. Dark deprivation also caused an increase in glucose levels, AST activity, and a decrease in blood levels of total protein and albumin. Constant lighting caused a rearrangement of the circadian rhythms of the area of nuclei, the area of the hepatocyte and nuclear-cytoplasmic ratio, Bmal1, per2, Clock expression, and led to destruction of Ki67 and p53 circadian rhythms in hepatocytes. Under conditions of constant lighting, the circadian rhythms of the content of lipids and glycogen in hepatocytes, ALT activity in the blood, and the content of total and direct bilirubin were also destroyed.
 CONCLUSIONS: It has been established that constant illumination causes a restructuring of the circadian rhythms of a number of studied parameters against the background of morphological and functional changes, indicating a decrease in the adaptive capacity of the liver.

Protective Effects of Melatonin on Hepatic Injury Due to Chronic Monosodium Glutamate Consumption in Adult Female Rats

In the present study, it was aimed to investigate the effects of Monosodium Glutamate (MSG) consumption on rat liver and the possible antioxidant and anti-inflammatory effects of melatoninin protecting against MSG-induced hepatic damage. Thirty two adult female rats were randomly divided into 4 groups. For 30 days, MSG (2g/kg/day) or melatonin (4mg/kg/day) was given daily in drinking water or both melatonin and MSG were given simultaneously at the same doses, while normal drinking water was given to the control group. Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) levels were investigated in the serum of rats decapitated at the end of the experiment. In liver sections, Hematoxylin-Eosin (H-E), Sirius red, Periodic Acid Schiff (PAS) staining for histopathological damage examination, Nuclear Factor-kappa B (NF-κB), smooth muscle a-actin [alpha-Smooth Muscle Actin (a-SMA)], NADPH Oxidase (NOX-2), Transforming Growth Factor (TGF)-β1, SMAD2, SMAD7 immunohistochemistry were applied. At the end of the experiment, % body weight change in MSG group rats was high, and serum ALT and AST levels were increased compared to control group, while these levels weredecreased with melatonin administration. In addition, vacuolization in hepatocytes, dilatation in sinusoids, increase in Kupffer cells andinflammatory cell foci were detected in the MSG group. When melatonin wasadded to MSG, decreased hepatocyte glycogen content and SMAD7 immunoreactivity with increased a-SMA were observed along with improvements in NF-kB, NOX-2, TGF-β1, SMAD2 immunoreactivity. Our findings suggest that melatonin, with its antioxidant and anti-inflammatory effects, may be a potential agent to prevent liver damage that can be caused by MSG in the diet.

Histological and histochemical changes in liver tissue of young rats with hyperhomocysteinemia

Annotation. The decisive place in the synthesis and subsequent metabolism of homocysteine (Hcy) belongs to the liver, where, in particular, transsulfation and remethylation processes take place. It has been proven that organ tissue damage can cause hyperhomocysteinemia (HHcy). Changes in the structural and functional parameters of the liver tissue under the conditions of a significant and long-term increase in blood serum Hcy are still insufficiently studied. Modeling the state of chronic HHcy and studying the features of histological changes in liver tissue at different levels of structural organization is an urgent task. The aim of the research is to study morphological and histochemical changes in the liver tissue of young rats with HHcy. The experiment was carried out on 22 white non-linear young – aged 1-2 months, male rats. During the study, the animals were divided into two groups – control and experimental. Chronic persistent HHcy was modeled by administering thiolactone Hcy in a dose of 200 mg/kg of body weight intragastrically for 60 days to the rats of the experimental group. Histological preparations were studied using a SEO SСAN light microscope and photo-documented using a Vision CCD Camera. Succinate dehydrogenase was detected histochemically according to the Nakhlas method. To study the specifics of glycogen accumulation in hepatocytes, sections were stained using Schiff's reagent, after preliminary treatment with iodic acid (PAS reaction) in the Shabadash modification. It was established that the administration of thiolactone Hcy to young rats at a dose of 200 mg/kg led to impaired blood supply, destructive changes and growth of connective tissue in the liver. Moderate changes in the hepatocyte plates organization, a decrease in the mitotic activity of hepatocytes, and the development of fatty and vacuole-hydropic dystrophy were recorded. Histochemical studies of the liver of animals of the research group established a decrease in the activity of the succinate dehydrogenase enzyme and glycogen content in hepatocytes.

Prenatal, lactation and postnatal effects of lead acetate on histological, histochemical and hepatic indices of liver of male offspring wistar rats

The aim of this study was to investigate the possible effects of maternal administration to lead acetate on the morphological structure of the liver; AST, ALT, ALP and GGT levels and glycogen content of hepatocytes of male offspring wistar rats. Female rats were exposed to 0.2% lead acetate in drinking water and the study was performed on their male offspring (7 groups). To evaluate the levels of liver enzymes, blood samples were taken from rats after anesthesia. After dissection, to study its morphological structure and glycogen content of hepatocytes, liver tissue was isolated and transferred to 10% formalin. To measure the levels of hepatic enzymes; AST, ALT, ALP and GGT; serum samples were evaluated. For histological examinations, liver tissue samples were embedded in paraffin after tissue processing and 3 μm thickness sections were prepared from them and then H&E and PAS staining was performed. The results showed that exposure to 0.2% lead acetate induced significant changes in liver enzyme levels in different experimental groups.

Dynamics of the Glycogen β-Particle Number in Rat Hepatocytes during Glucose Refeeding.

Glycogen is an easily accessible source of energy for various processes. In hepatocytes, it can be found in the form of individual molecules (β-particles) and their agglomerates (α-particles). The glycogen content in hepatocytes depends on the physiological state and can vary due to the size and number of the particles. Using biochemical, cytofluorometric, interferometric and morphometric methods, the number of β-particles in rat hepatocytes was determined after 48 h of fasting at different time intervals after glucose refeeding. It has been shown that after starvation, hepatocytes contain ~1.6 × 108 β-particles. During refeeding, their number of hepatocytes gradually increases and reaches a maximum (~5.9 × 108) at 45 min after glucose administration, but then quickly decreases. The data obtained suggest that in cells there is a continuous synthesis and degradation of particles, and at different stages of life, one or another process predominates. It has been suggested that in the course of glycogenesis, pre-existing β-particles are replaced by those formed de novo. The main contribution to the deposition of glycogen is made by an increase in the glucose residue number in its molecules. The average diameter of β-particles of glycogen during glycogenesis increases from ~11 nm to 21 nm.

O67: PERFUSATE GLUCOSE REFLECTS TISSUE GLYCOGENATION DURING LIVER PERFUSION

Abstract Introduction Normothermic machine perfusion (NMP) is a method of organ preservation that aims to replicate the physiological environment, achieved by perfusing the livers with a blood-based perfusate at physiological inflow pressures and temperature. NMP also permits viability assessment through evaluation of the perfusate flow rates through the portal vein and hepatic artery. In addition to this, biochemical assessment and perfusate gas analysis can be performed to provide insights into the metabolic activity of the liver. Method Discarded human liver grafts (n=6), were perfused for 24 hours. Core biopsies and perfusate samples were taken from each liver at 5 distinct time intervals over 24 hours. Core biopsies were fixed and stained with periodic acid-Schiff and analysed with Leica software to provide a quantitative estimate of the hepatocellular glycogen content. Result Hepatic glycogen concentration rose during the first hour, followed by a steady decline thereafter until the end of perfusion. Contrary to our initial hypothesis that glucose concentration within the circuit would show an inverse relationship to glycogen stores in the liver cells, we found that glucose concentration closely followed the same trend. Conclusion Change in hepatocyte glycogen content provides an important insight into the synthetic function of a liver destined for transplant. Our research suggests that glucose concentration can be used as a surrogate marker for the synthetic function of a liver on NMP and provides valuable information on the glycogen-synthesising capability of the hepatocytes. In future, this could potentially aid the decision-making process with regards to liver graft transplant viability. Take-home message Perfusate glucose concentration could provide an insight into the viability of liver transplants

THE RAT’S LIVER MORPHOLOGY AT LONGEST FEEDING WITH JUNK FOOD

The effect of the regular use of junk-food on the morphological and functional state of the liver was studied in mature females Wistar rats. Animals of experimental groups received for a 100 days a diet that included potato chips and sweet caffeine-containing soft drinks. In the liver of rats of experimental groups dystrophic changes in hepatocytes - small-, medium- and large-droplet vacuolar dystrophy from weak to severe, were detected. Compared to the control group, rats, which consumed junk-food, had a decrease in the cell and nuclei volume and glycogen content of hepatocytes. Revealed changes reflect alteration of the liver metabolic balance and point to the development of functional changes, that provide carbohydrate-fat, water-electrolyte and protein metabolism.

Light and Electron Microscopic Study of the Effect of Orlistat on the Liver of Adult Male Albino Rats and the Possible Protective Role of <i>β</i>-Carotene

Orlistat is a safe and effective drug to treat obesity by acting as a pancreatic and gastric lipase inhibitor, resulting in reduction in fat absorption. There is also concern that it may be linked with an increased threat of serious hepatic incidents. The present work was carried out to study the effect of orlistat on the histological, immunohistochemical and electron microscopic structure of the liver in the adult male albino rats and the possible protective role of β-carotene administration. Forty adult albino rats were subjected to experiment for two weeks as follows: group 1 (control), group II, each animal received 0.52 mg/kg bw/day β-Carotene, group III, each animal received orlistat 32 mg/kg/day, and group IV received β-Carotene, 1hour before the administration of orlistat at same dose of group II & III. The liver from each animal was dissected out and processed for histological, (light and electron microscopic study). The result of Hep-Par1 for immunohistochemistry was statistically analyzed. The results showed that orlistat treated group displayed variable disturbance of liver architecture, from dilatation, congested central and portal veins, branching of bile ductules, mononuclear cellular infiltration, areas of hemorrhages, cytoplasmic vacuolation and pyknotic nuclei. The most obvious changes were that degenerative changes in hepatocytes led to depletion of glycogen content of hepatocytes. Hep Par-1 revealed a wide area of negative immune expression around the central vein and in some hepatocytes. Other hepatocytes expressed weak reaction. Ultrastructure examination displayed hepatocytes with swollen mitochondria and others with an electron-dense matrix. The combined treatment of β-Carotene and orlistat led to a marked improvement in most of the previously mentioned changes. It was concluded that orlistat-induced hepatic toxicity. Thus, clinicians should cautiously monitor their patients for signs of hepatic dysfunction. Using an antioxidant such as β-Carotene decreased the toxicity of orlistat.

Glycogen content in hepatocytes is related with their size in normal rat liver but not in cirrhotic one

Hepatocytes differ from one another by the degree of the ploidy, size, position in the liver lobule, and level of the DNA-synthetic processes. It is believed, that the cell size exerts substantial influence on the metabolism of the hepatocytes and the glycogen content in them. The aim of the present study was to test this hypothesis. Dry weight of hepatocytes, their ploidy and glycogen content were determined in the normal and the cirrhotic rat liver. Liver cirrhosis in rats was produced by chronic inhalation of CCl4 vapours in the course of 6 months. A combined cytophotometric method was used. Dry weight of the cell, its glycogen and DNA content were successively measured on a mapped preparation. Hepatocytes of each ploidy class in the normal and the cirrhotic rat liver accumulated glycogen at the same rate. In the normal liver, there was a distinct correlation between the size of hepatocytes and glycogen content in them. This correlation was observed in each ploidy class, and was especially pronounced in the class of mononucleate tetraploid hepatocytes. In the cirrhotic liver, there was no correlation between the size of the cells and their glycogen content. The impairment of liver lobular structure probably explains the observed lack of correlation between hepatocyte size and their glycogen content in the cirrhotic liver. © 2016 International Society for Advancement of Cytometry.

Dynamics of proglycogen and macroglycogen in hepatocytes of normal and cirrhotic rat liver at various stages of glycogenesis

The content and structure of glycogen in hepatocytes of normal and cirrhotic rat liver were examined at different time intervals after glucose administration to starving animals. We used an original cytofluorimetric method for detection and quantification of proglycogen (PG) and macroglycogen (MG) of isolated hepatocytes. The method is based on the use of reagents of the Schiff type with different spectral characteristics. The content of MG in hepatocytes of control rats was increased by 52% (p < 0.01) as early as after 10 min. The MG content in the cirrhotic liver cells was increased by 43% (p < 0.05) only 20 min after glucose administration to the starving animals. The correlation coefficient between MG content and the total glycogen content at various stages of glycogenesis in rats of both groups was from 0.90 to 0.99 (p < 0.001). Increase in the PG content in hepatocytes of control rats was observed in intervals of 10–30 and 45–75 min. The PG content in cirrhosis was increased only in 60 min after the beginning of glycogenesis, but in 120 min it was 1.5 times higher than the control values (p < 0.001). The correlation coefficients between PG and the total glycogen content in the cells were on average 0.86 (p < 0.001) and 0.77 (p < 0.001) in the control and experimental groups, respectively. Thus, the change in the total glycogen content in hepatocytes of normal and cirrhotic liver are associated mainly with changes in the MG level. The contribution of PG was most significant in normal liver at the beginning of glycogenesis (10–30 min); in cirrhotic liver, at later stages (75–120 min).

Hepatocytes of cirrhotic rat liver accumulate glycogen more slowly than normal ones.

To investigate the accumulation of glycogen in cirrhotic rat liver at several time intervals after per os administration of glucose to fasted animals. Liver cirrhosis was produced by inhalation of the hepatotropic poison CCl4. Glycogen concentration in the liver was determined biochemically. Glycogen content in hepatocytes was measured cytofluorimetrically in the smears stained with a fluorescent PAS reaction. Glycogen content in the hepatocytes of the portal and the central zone of the liver lobule was determined by absorption cytophotometry. Rats poisoned with CCl4 for 6months developed typical liver cirrhosis characterized by a fourfold (p<0.001) increase in the proportion of the connective tissue. In the cirrhotic rats fasted for 48h, glycogen concentration in the liver and glycogen content in hepatocytes were lower as compared with the control by 36 and 27% (p<0.01), respectively. According to data obtained by different methods, the control animals accumulated glycogen at a high rate. In particular, the glycogen content in hepatocytes increased by 34% after 10min (p<0.01). In the cirrhotic rats, glycogen content remained at the same level for 20min. In both groups of animals, hepatocytes of the portal zone accumulated more glycogen than those of the central zone. Glycogen accumulation in cirrhotic rats starts after a delay and proceeds at a lower rate than in the norm.

The reduction of glycogen in the liver induced by chronic intravenous heroin abuse

Introduction. The liver plays a key role in the removal of lipophyllic substances from the plasma, including both morphine and its derivative heroin. Intravenous heroin abuse leads to liver damages, so that the effects of heroin intake are the most marked and characteristic in the liver. Objective. A histochemical and ultrastructural study of the liver, particularly hepatocyte glycogen content, should provide a precise insight into the type and degree of liver damage induced by intravenous heroin abuse. Methods. The study included the analysis of 50 autopsies, 40 from the group of intravenous heroin abusers and 10 control autopsies. Paraffin sections, 5 µm thick, were stained by PAS method for deposited glycogen staining. The ultrastructural investigation was performed on transmission electron microscope. Results. Glycogen amount was reduced proportionally to the severity and distribution of degenerative and necrotic hepatocytic lesions. Regarding deposited glycogen depletion in particular acinar zones, glycogen was most preserved in zone 1 (30% of studied cases), then in zone 3 (preserved in 25%), while the depletion was most significant in intermediary zone (preserved in 5%). In the intravenous heroin abusers group of up to 2 years glycogen was preserved in the acinar zones 1, 2 and 3 in 43%, 30% and 57%, respectively; in the group of over 10 years glycogen preservation in zone 1 was 25% and in other zones 0%. Conclusion. Intravenously administered heroin directly influences glycogen reduction in the hepatocytes, and the effect is potentiated by morphologic changes in the liver due to intravenous heroin abuse. Glycogen depletion in the hepatocytes reduces energy reserves in these cells and causes cell death, which is an important segment of general liver injury in intravenous heroin abusers. The degree of reduction of glycogen depositions is proportional to the duration of intravenous heroin abuse

Biphasic effects of dexamethasone on glycogen metabolism in primary cultured rat hepatocytes

Glucocorticoids (GC), the basic function of which is modulating carbohydrates metabolism, play a critical role in stress response by enhancing the organism's resistance. It is widely believed that they could promote glycogen synthesis. However, it is doubtful whether GC can still stimulate glycogen deposition in stress response, as it is known that glucose is imperatively needed at that time. Here, we used primary cultured rat hepatocytes to investigate the effects of GC on glycogen metabolism in vitro to exclude other influences in stress. The results showed that dexamethasone (Dex) played biphasic effects on hepatocytes glycogen metabolism depending on its dosage and the duration of stimulation. Dex could decrease glycogen content of hepatocytes in the higher concentration within a relatively shorter period of time, which could not be blocked by cycloheximide. Therefore, dual roles in hepatic glycogen metabolism played by GC were demonstrated, and a non-genomic mechanism might be involved in the glycogenolytic action of GC. We postulated that the biphasic effects of GC on hepatic glycogen metabolism might be of important significance in stress response.

Effects of a New Bioactive Lipid-Based Drug Carrier on Cultured Hepatic Stellate Cells and Liver Fibrosis in Bile Duct-Ligated Rats

In the fibrotic liver, hepatic stellate cells (HSC) produce large amounts of collagen and secrete variety of mediators that promote development of fibrosis in this organ. Therefore, these cells are considered an attractive target for antifibrotic therapies. We incorporated the bioactive lipid dilinoleoylphosphatidylcholine (DLPC) into the membrane of liposomes, and then we evaluated its effect on hepatic stellate cell activation and liver fibrosis. To target DLPC-liposomes to HSC, human serum albumin modified with mannose 6-phosphate (M6P-HSA) was coupled to the surface of these liposomes. In vitro, the effects of the carrier were determined in primary cultures of HSC, Kupffer cells, and liver endothelial cells using real-time reverse transcription-polymerase chain reaction. In vivo DLPC-liposomes were tested in bile duct-ligated rats. Targeted M6P-HSA-DLPC-liposomes and DLPC-liposomes significantly reduced gene expression levels for collagen 1alpha1, alpha-smooth muscle actin (alpha-SMA), and transforming growth factor-beta (TGF-beta) in cultured HSC. In fibrotic livers, DLPC-liposomes decreased gene expression for TGF-beta and collagen 1alpha1 as well as alpha-SMA and collagen protein expression. In contrast, M6P-HSA-DLPC-liposomes enhanced expression of profibrotic and proinflammatory genes in vivo. In cultured Kupffer and endothelial cells M6P-HSA liposomes influenced the expression of proinflammatory genes. Both types of liposomes increased hepatocyte glycogen content in fibrotic livers, indicating improved functionality of the hepatocytes. We conclude that DLPC-containing liposomes attenuate activation of cultured HSC. In fibrotic livers, M6P-HSA-mediated activation of Kupffer and endothelial cells probably counteracts this beneficial effect of DLPC-liposomes. Therefore, these bioactive drug carriers modulate the activity of all liver cells during liver fibrosis.

Intracellular changes in rat hepatocytes after intratracheal administration of highly dispersed silicon dioxide and uridine effects on these changes

Rat hepatocytes were examined under electron microscope at early terms after intratracheal administration of highly dispersed silicon dioxide powder against the background of uridine treatment. Penetration of powder particles into hepatocyte cytoplasm, nuclei, mitochondria, and peroxisomes and development of bacteria in these cells were observed. Uridine reduced the destructive effect of powder on the organelles, increased glycogen content in hepatocytes, and inhibited the formation of capsulated bacterial forms in these cells.

Fasting modulates metabolic responses to cortisol, GH and IGF‐I in Arctic charr hepatocytes

Hepatocytes in primary culture from fed and 2 month fasted Arctic charr Salvelinus alpinus were exposed to physiological doses of either cortisol, salmon growth hormone (GH), salmon insulin‐like growth factor‐I (IGF‐I) or a combination of salmon GH and salmon IGF‐I. Fasting significantly lowered medium glucose levels compared to the fed fish, but had no significant effects on hepatocyte glycogen content or on the activities of enzymes involved in the intermediary metabolism. Cortisol treatment had no effect on hepatocyte glycogen content or on the enzyme activities investigated, but resulted in a significant increase in medium glucose concentration in hepatocytes isolated from fasted, but not fed fish. GH and IGF‐I treatments, both singly and in combination, significantly increased the glycogen content of hepatocytes isolated from fed fish, with less pronounced effects on hepatocytes isolated from fasted fish. The combination of GH and IGF‐I significantly increased lactate dehydrogenase activity regardless of the feeding state and significantly reduced the phosphenolpyruvate carboxykinase activity and medium glucose concentration in hepatocytes isolated from fed fish. Further, GH and IGF‐I significantly increased the activities of alanine aminotransferase and aspartate aminotransferase in hepatocytes isolated from fasted fish, but not fed fish. There were no effects of GH, IGF‐I, or their combination, on glucose 6‐phosphate dehydrogenase or 3‐hydroxyacyl‐CoA dehydrogenase activities. The results demonstrated that nutritional status of the animal modulates hepatocyte responsiveness to metabolic hormones, and suggested a role for GH and IGF‐I in hepatic glycogen conservation.

Warm Hepatic Ischemia in Pigs: Effects of L-Arginine and Oligotide Treatment

Reperfusion injury represents a key event leading to graft nonfunction. Maintaining adequate nitric oxide levels and stimulating vasodilator synthesis can probably minimize endothelial damage. The aim of this study was to investigate the effect of L-arginine, a substrate of nitric oxide synthesis, and oligotide, a promoter of prostacyclin synthesis, on liver function and morphology after warm ischemia-reperfusion injury. After constructing a side-to-side portacaval shunt, ischemia was induced by clamping the hepatic hilum for 2 h above the shunt, in 19 female pigs divided into a control group ( n = 7), an L-arginine treatment group ( n = 6), and an oligotide treatment group ( n = 6). Liver function tests and measurements of serum and red blood cell malondialdehyde and plasma nitric oxide levels were performed before reperfusion and at 1, 10, 60, and 120 min after reperfusion. Liver biopsies, taken before reperfusion and at 30 min and 7 days after reperfusion, were analyzed for tissue malondialdehyde, histological-ultrastructural features, and apoptosis evaluation. Thirty minutes after reperfusion, liver malondialdehyde, sinusoidal congestion, necrosis, and apoptosis were significantly lower in the L-arginine group than in the controls ( p < .05). On postoperative day 7, tissue malondialdehyde decreased, while plasma nitric oxide and hepatocyte glycogen content were increased in the L-arginine group compared to controls ( p < .05). This study demonstrates the protective effect of L-arginine on hepatic lipoperoxidation and liver morphology in a pig model of warm ischemia-reperfusion injury. The increased plasma levels of nitric oxide a week after ischemia-reperfusion injury support the hypothesis that it has a role in preventing liver damage. The same beneficial effect was not confirmed for oligotide.

Restoration of the glycogen-forming function of hepatocytes in rats with liver cirrhosis is facilitated by a high-carbohydrate diet

Using cytofluorimetric and biochemical methods, the content of glycogen and its labile and stable fractions, as well as activities of glucose-6-phosphatase (EC 3.1.3.9), glycogen phosphorylase (EC 2.4.1.1) and glycogen synthase (EC 2.4.1.11) were determined in the rat liver for 6 months after chronic poisoning of the animals with CCl4 and then at 1, 3, and 6 months after the end of the poisoning. One group of rats was given a standard diet, the other, a high-carbohydrate diet. The 6-month long chronic intoxication with CCl4 was shown to produce development of typical liver cirrhosis characterized by a 2.8-fold increase in the total glycogen content in hepatocytes as compared with normal cells, by a fall in the glycogen labile fraction (from 85 to 53% of the total glycogen) as well as by decreases in the activities of glycogen phosphorylase and glucose-6-phosphatase by 25 and 82% respectively. The structural rehabilitation occurred faster and more completely at the cellular level than at the tissue level. Functional variables of the cirrhotic liver tissue also recovered, after cessation of poisoning, faster and more completely than the liver structure at the tissue level: glycogen levels in hepatocytes fell dramatically, the labile: stable glycogen fraction ratio recovered completely, and the activity of glycogen phosphorylase rose to the level characteristic of the normal liver. Use of the high-carbohydrate diet promoted a somewhat faster and more complete recovery of hepatic structure and function.

Functional activity of human hepatocytes under traumatic disease

Absorption and fluorescent cytophotometry techniques were applied to studies of RNA as well as of total glycogen and its fractions as the parameters of functional activity of the hepatocytes in patients with severe mechanical trauma, both with and without autointoxication (AI). Slides were stained with gallocyanine-chromalums to determine the RNA content and were processed by the fluorescent PAS-reaction for the glycogen content. To trace the dynamics of RNA and glycogen contents in the liver punction biopsies were done in the same patients. A quick increase in the RNA content took place in both groups of patients at the first period (within the first 3 days) of traumatic disease. At the second period of disease the hepatocyte RNA content in patients without AI was found to decrease up to the initial level whereas that in patients with AI increased on the average by 36% of the initial values. The total glycogen content in hepatocytes of all the patients changed insignificantly in the course of disease but its labile fraction in patients with AI decreased to 70% of the total. The increase of hepatocyte synthetic activity and the maintenance of the high glycogen level are indicative of the large compensatory potential of the liver that enables it to carry an intensive functional load under AI conditions.

3,3′,4,4′-Tetrachlorobiphenyl affects cortisol dynamics and hepatic function in rainbow trout

This study investigates the impact of 3,3′,4,4′-tetrachlorobiphenyl (TCBP), a polychlorinated biphenyl (PCB) congener and cytochrome P-450 inducer, on cortisol dynamics in rainbow trout ( Oncorhynchus mykiss). Trout were given either an intraperitoneal implant of corn oil alone or corn oil containing TCBP (5 mg kg −1 body weight) and sampled 6 weeks later. TCBP-implanted fish had significantly lower condition factor and plasma glucose concentration, whereas plasma cortisol and protein, and hepatocyte protein concentration and liver ethoxyresorufin- O-deethylase (EROD) activity was significantly higher compared with the sham group. There was no significant difference in plasma lactate and amino acid concentration, hepatocyte glycogen content or liver cytosolic cortisol binding affinity or capacity between the two groups. [ 3H]Cortisol uptake was significantly higher in hepatocytes isolated from TCBP-treated fish compared with the sham fish. Also, our preliminary results suggest that the catabolism of [ 3H]cortisol by hepatocytes of TCBP-treated fish was enhanced as noted by a decrease in cortisol-specific radioactivity and an increase in tetrahydrocortisone (a cortisol metabolite) specific radioactivity. These results support a role for TCBP in enhancing cortisol clearance by hepatocytes of trout and suggest that toxicants like PCBs may impair the ability of trout to elicit a physiological response normally associated with cortisol stimulation.