Total Liver Protein Research Articles

Zinc protecting effects on diabetic nephropathy

Palm oil is thermally oxidized to increase its palatability and this has been a usual practice in most homes. This study sought to assess the biochemical responses of rats to thermally oxidized palm oil diets. Therefore, Wistar strain albino rats (Rattus norveigicus) were fed with fresh palm oil (control) and thermally oxidized palm oil (test groups) diets and water ad libitum for 30 days. Then, the malondialdehyde (MDA) contents and total protein of the plasma and liver were determined. Subsequently, the plasma liver function markers [alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), albumin (ALB) and total bilirubin (TBIL) ] and the lipid profile [triglyceride (TRIG), total cholesterol (T-CHOL), high density lipoprotein (HDL-CHOL) and low density lipoprotein (LDL-CHOL) ] were assayed. The results of the study revealed that there was a significant decrease (P < 0.05) in the plasma and liver total protein, ALB, TRIG and HDL-CHOL of the test groups when compared with the control. Conversely, there was a significant increase (P < 0.05) in the activities of ALT, AST and ALP, TBIL, T-CHOL, LDL-CHOL and plasma/liver MDA of the test groups when compared with the control. These effects were most pronounced in rats fed with 20 min-thermally oxidized palm oil diet. Hence, consumption of thermally oxidized palm oil diets had deleterious effects on biochemical indices in rats. Therefore, cooking with and/or consumption of palm oil subjected to heat treatment for several long periods of time should be discouraged in our homes as this might have deleterious effects on human health.

Increase in skeletal muscle protein content by the beta-2 selective adrenergic agonist clenbuterol exacerbates hypoalbuminemia in rats fed a low-protein diet.

This investigation examined how the nutritional status of rats fed a low-protein diet was affected when the animals were treated with the beta-2 selective agonist clenbuterol (CL). Males (4 weeks old) from an inbred, specific-pathogen-free strain of hooded rats maintained at the Dunn Nutritional Laboratory were used in the experiments (N = 6 rats per group). CL treatment (Ventipulmin, Boehringer-Ingelheim Ltd., 3.2 mg/kg diet for 2 weeks) caused an exacerbation of the symptoms associated with protein deficiency in rats. Plasma albumin concentrations, already low in rats fed a low-protein diet (group A), were further reduced in CL rats (A = 25.05 +/- 0.31 vs CL = 23.64 +/- 0.30 g/l, P < 0.05). Total liver protein decreased below the level seen in either pair-fed animals (group P) or animals with free access to the low-protein diet (A = 736.56 +/- 26 vs CL = 535.41 +/- 54 mg, P < 0.05), whereas gastrocnemius muscle protein was higher than the values normally described for control (C) animals (C = 210.88 +/- 3.2 vs CL = 227.14 +/- 1.7 mg/g, P < 0.05). Clenbuterol-treated rats also showed a reduction in growth when compared to P rats (P = 3.2 +/- 1.1 vs CL = -10.2 +/- 1.9 g, P < 0.05). This was associated with a marked decrease in fat stores (P = 5.35 +/- 0.81 vs CL = 2.02 +/- 0.16 g, P < 0.05). Brown adipose tissue (BAT) cytochrome oxidase activity, although slightly lower than in P rats (P = 469.96 +/- 16.20 vs CL = 414.48 +/- 11.32 U/BAT x kg body weight, P < 0.05), was still much higher than in control rats (C = 159.55 +/- 11.54 vs CL = 414.48 +/- 11.32 U/BAT x kg body weight, P < 0.05). The present findings support the hypothesis that an increased muscle protein content due to clenbuterol stimulation worsened amino acid availability to the liver and further reduced albumin synthesis causing exacerbation of hypoalbuminemia in rats fed a low-protein diet.

Retinol uptake and metabolism, and cellular retinol binding protein expression in an in vitro model of hepatic stellate cells.

Liver is a major site of retinoid metabolism and storage, and more than 80% of the liver retinoids are stored in hepatic stellate cells. These cells represent less than 1% of the total liver protein, reaching a very high relative intracellular retinoid concentration. The plasma level of retinol is maintained close to 2 microM, and hepatic stellate cells have to be able both to uptake or to release retinol depending upon the extracellular retinol status. In view of their paucity in the liver tissue, stellate cells have been studied in primary cultures, in which they loose rapidly the stored lipids and retinol, and convert spontaneously into the activated myofibroblast phenotype, turning a long-term study of their retinol metabolism impossible. We have analyzed the retinol metabolism in the established GRX cell line, representative of stellate cells. We showed that this cell line behaves very similarly, with respect the retinol uptake and release, to primary cultures of hepatic stellate cells. Moreover, we showed that the cellular retinol binding protein (CRBP-I) expression in these cells, relevant for both uptake and esterification of retinol, responds to the extracellular retinol status, and is correlated to the retinol binding capacity of the cytosol. Its expression is not associated with the overall induction of the lipocyte phenotype by other agents. We conclude that the GRX cell line represents an in vitro model of hepatic stellate cells, and responds very efficiently to wide variations of the extracellular retinol status by autonomous controls of its uptake, storage or release.

Effect of varying amino acid levels on protein metabolism in nephrotic rats during total parenteral nutrition.

In an attempt to determine appropriate diet in nephrotic syndrome, nephrotic rats, induced by puromycin aminonucleoside, were nourished by total parenteral nutrition fluid containing the same energy, but three different levels (1.65, 3.3, and 6.6%) of amino acids for 7 d. The fractional rate of total protein synthesis in the liver was determined by injecting a flooding dose of [3H]phenylalanine. The proportion of newly synthesized proteins retained and exported by the liver was estimated by injecting a tracer dose of [14C]leucine and then measuring the protein radioactivity remaining in the liver and present in the plasma after secretion was completed. Nephrotic animals synthesized more protein than control animals. Although the absolute synthesis rates of total protein in liver were increased with increasing amino acid administration, the absolute rates of synthesis of albumin were higher in the 3.3% group than in the other groups in nephrotic rats. However, kidney protein synthesis in nephrotic rats was higher in the 1.65% group than in the 3.3% group. Interestingly, the 3.3% group revealed the smallest urinary excretion of total protein and albumin. In addition, in the 3.3% group, plasma concentrations of total protein and albumin were higher, and plasma concentrations of total cholesterol and triglyceride were lower than in other groups. It was concluded that the 3.3% group, corresponding to a normal protein diet, has the greatest salutary effect on urinary protein excretion, followed by protein and lipid metabolism, in nephrotic rats. Not only protein intake but also the energy:protein ratio are important for diet therapy in nephrotic animals. The technique of total parenteral nutrition may be useful in defining the factors involved in glomerular permeability or permselectivity and intracellular protein metabolism.

Prenatal alcohol exposure affects galactosyltransferase activity and glycoconjugates in the Golgi apparatus of fetal rat hepatocytes.

Prenatal exposure to alcohol affects the morphological, structural, and functional features of the Golgi apparatus (GA), thus altering the glycosylation process in fetal hepatocytes. To elucidate the cellular mechanisms underlying these alterations, we have studied the effect of alcohol exposure in utero on the activity of liver galactosyltransferase, an enzyme involved in the glycosylation process, and on the hepatic glycoprotein sugar composition. For this, livers from 21-day-old fetuses obtained from control and ethanol-fed rats were used. Galactosyltransferase (GT) activity was determined in isolated GA cis and trans fractions. Colloidal gold-labeled lectin cytochemistry was used to analyze sugar residues in hepatocytes at the subcellular level. Finally, the integrity of the GA after alcohol treatment was assessed by electron microscopy and by evaluating the distribution of the Golgi beta-COP, a protein involved in vesicular trafficking. Prenatal alcohol exposure induces a significant increase in both liver weight and total protein content in the trans Golgi. Moreover, this treatment decreases the activity of galactosyltransferase, increases alpha-L-Fuc residues, and reduces the number of alpha-Man, GlcNAc(beta1,4,GlcNAc)1,2, GalNAc alpha1,3GalNAc, alpha-GalNAc, and a-Gal residues. Alcohol exposure also causes the Golgi cisternae to disappear in about 30% of the hepatocytes, and reduces 75% the number of anti-Golgi beta-COP protein binding sites. Our results suggest that the decrease in galactosyltransferase activity, the alterations in the oligosaccharide chain composition, and the reduction in the amount of Golgi beta-COP protein could be involved in the alterations in the glycosylation process, as well as in the accumulation of hepatic proteins observed after prenatal alcohol exposure. These alterations could contribute, therefore, to the alcohol-induced injury in the developing liver.

Prenatal alcohol exposure affects galactosyltransferase activity and glycoconjugates in the Golgi apparatus of fetal rat hepatocytes

Prenatal exposure to alcohol affects the morphological, structural, and functional features of the Golgi apparatus (GA), thus altering the glycosylation process in fetal hepatocytes. To elucidate the cellular mechanisms underlying these alterations, we have studied the effect of alcohol exposure in utero on the activity of liver galactosyltransferase, an enzyme involved in the glycosylation process, and on the hepatic glycoprotein sugar composition. For this, livers from 21-day-old fetuses obtained from control and ethanol-fed rats were used. Galactosyltransferase (GT) activity was determined in isolated GA cis and trans fractions. Colloidal gold-labeled lectin cytochemistry was used to analyze sugar residues in hepatocytes at the subcellular level. Finally, the integrity of the GA after alcohol treatment was assessed by electron microscopy and by evaluating the distribution of the Golgi β-COP, a protein involved in vesicular trafficking. Prenatal alcohol exposure induces a significant increase in both liver weight and total protein content in the trans Golgi. Moreover, this treatment decreases the activity of galactosyltransferase, increases α-L-Fuc residues, and reduces the number of α-Man, GlcNAc(β1,4,GlcNAc)1,2, GalNAc α1,3GalNAc, α-GalNAc, and a-Gal residues. Alcohol exposure also causes the Golgi cisternae to disappear in about 30% of the hepatocytes, and reduces 75% the number of anti-Golgi β-COP protein binding sites. Our results suggest that the decrease in galactosyltransferase activity, the alterations in the oligosaccharide chain composition, and the reduction in the amount of Golgi β-COP protein could be involved in the alterations in the glycosylation process, as well as in the accumulation of hepatic proteins observed after prenatal alcohol exposure. These alterations could contribute, therefore, to the alcohol-induced injury in the developing liver.(Hepatology 1997 Feb;25(2):343-50)

Hepatic protein synthesis in the sheep: effect of intake as monitored by use of stable-isotope-labelled glycine, leucine and phenylalanine.

Rates of protein synthesis for the liver, plasma albumin and total plasma protein were quantified in sheep either offered a supra-maintenance intake or fasted for 3 d. The technique of continuous infusion over a 12 h period was employed with the simultaneous infusion of [1-13C]glycine, [1-13C]leucine and [2H5]phenylalanine. Blood and plasma samples were removed at timed intervals from the hepatic portal and hepatic veins plus the aorta. Enrichments of the free amino acids (AA) were determined in all blood and plasma samples as was the protein-bound AA in an apolipoprotein B100 extract. Protein-bound phenylalanine enrichments were also measured in albumin and total protein from plasma plus samples from liver biopsies. The apolipoprotein B100 enrichments agreed well with those of the free AA in hepatic (and hepatic portal) plasma but were lower than for arterial free AA and greater than liver homogenate free AA. This adds support to the concept that export proteins may preferentially use AA directly from extracellular sources. Intake had no significant effect on constitutive liver protein synthesis and the values agreed well with those obtained by other isotopic approaches. There were, however, significant declines, based on hepatic venous free phenylalanine enrichment, at the lower intake in both the fractional (3.4 v. 4.7% per d; P = 0.024) and absolute (2.4 v. 4.2 g/d; P = 0.011) synthesis rates of albumin, which matched the estimated decrease in total plasma albumin content (52 v. 67 g, P < 0.01). In contrast, there was a smaller reduction in total plasma protein mass (145 v. 151 g, P = 0.035) with no observed significant difference in kinetic parameters. Albumin synthesis was calculated to account for a maximum of 17% of total liver protein synthesis in the fed condition and this may fall to 8% during moderate fasts.

The synthesis rates of total liver protein and plasma albumin determined simultaneously in vivo in humans

Although the metabolism of liver-derived plasma proteins such as albumin has been extensively studied, human hepatic protein synthesis as a whole has not been well characterized, because a reproducible model for obtaining human liver tissue has not been available. In this study, the fractional synthesis rates of total liver protein and albumin in vivo were determined simultaneously in nine subjects undergoing elective laparoscopic cholecystectomy. L-[2H5]phenylalanine (45 mg/kg body wt) was administered for 10 minutes intravenously. Blood samples were collected at regular intervals for 90 minutes and a liver biopsy specimen was taken at 35 +/- 7 minutes. The enrichments of plasma free phenylalanine, plasma albumin, and total liver protein were measured with gas chromatography mass spectrometry (GC-MS). The fractional synthesis rate (FSR) of total liver protein was 24.7 +/- 3.1 %/d (mean +/- SD), and that of albumin was 5.9 +/-1.2%/d. The amount of albumin synthesized per day (absolute synthesis rate, ASR) was 109 +/- 21 mg/kg body wt. No correlation between FSR of total liver protein and ASR of albumin was found. It is concluded that the technique of obtaining liver tissue specimens during laparoscopic surgery may serve as a human in vivo model to study total liver protein synthesis. The fractional synthesis rate of total liver proteins (stationary and exported), equals approximately 25% of the liver protein content daily. Within the range of values of this study, the absolute synthesis rate of albumin was not correlated to the fractional synthesis rate of total liver protein.(Hepatology 1997 Jan;25(1):154-8)

The synthesis rates of total liver protein and plasma albumin determined simultaneously in vivo in humans.

Although the metabolism of liver-derived plasma proteins such as albumin has been extensively studied, human hepatic protein synthesis as a whole has not been well characterized, because a reproducible model for obtaining human liver tissue has not been available. In this study, the fractional synthesis rates of total liver protein and albumin in vivo were determined simultaneously in nine subjects undergoing elective laparoscopic cholecystectomy. L-[2H5]phenylalanine (45 mg/kg body wt) was administered for 10 minutes intravenously. Blood samples were collected at regular intervals for 90 minutes and a liver biopsy specimen was taken at 35 +/- 7 minutes. The enrichments of plasma free phenylalanine, plasma albumin, and total liver protein were measured with gas chromatography mass spectrometry (GC-MS). The fractional synthesis rate (FSR) of total liver protein was 24.7 +/- 3.1 %/d (mean +/- SD), and that of albumin was 5.9 +/-1.2%/d. The amount of albumin synthesized per day (absolute synthesis rate, ASR) was 109 +/- 21 mg/kg body wt. No correlation between FSR of total liver protein and ASR of albumin was found. It is concluded that the technique of obtaining liver tissue specimens during laparoscopic surgery may serve as a human in vivo model to study total liver protein synthesis. The fractional synthesis rate of total liver proteins (stationary and exported), equals approximately 25% of the liver protein content daily. Within the range of values of this study, the absolute synthesis rate of albumin was not correlated to the fractional synthesis rate of total liver protein.

Seasonal variations in the temperature acclimation response of the channel catfish, Ictalurus punctatus.

Channel catfish were collected on 11 different dates from October 1991 to July 1993 and acclimated in the laboratory to 7 degrees C, 15 degrees C, or 25 degrees C for 6 wk. Hepatosomatic index, mg protein mg-1 DNA, total liver DNA and protein, and the activities of liver glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, lactate dehydrogenase, and malate dehydrogenase were measured to examine seasonal variation in the acclimation response. Liver and muscle cytochrome oxidase and lactate dehydrogenase activities were measured to compare tissue-specific responses. Hepatosomatic indexes of fall and winter channel catfish were highest at 7 degrees C, with values at 15 degrees C higher than at 25 degrees C, while spring and summer fish had the highest values at 15 degrees C, with values at 7 degrees C higher than those at 25 degrees C. Acclimation patterns for total liver protein and DNA, mg protein mg-1 DNA, and glycogen were generally higher in cold temperatures but varied seasonally in an unpredictable manner. Glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and malate dehydrogenase demonstrated positive acclimation in the fall and winter; fish collected in the spring and summer showed little or inverse acclimation. Liver lactate dehydrogenase activity showed little or no positive compensation at any time of the year. Cytochrome oxidase activity showed positive acclimation in muscle but not liver. All liver enzymes, even those that showed marginal acclimation on a protein basis, showed positive acclimation when activity was expressed on a whole-liver basis.

P.64 The synthesis rates of total liver protein and albumindetermined simultaneously in vivo in man

P.64 The synthesis rates of total liver protein and albumindetermined simultaneously in vivo in man

The effect of cytochromes P4501A induction and inhibition on the disposition of the cognition activator tacrine in rat hepatic preparations.

1. The disposition of tacrine 1,2,3,4-tetrahydro-9-acridinamine monohydrochloride monohydrate (THA, Cognex), was studied using livers obtained from control, phenobarbital (PB), isosafrole (ISO), and 3-methycholanthrene (3-MC) treated rats. 2. Pretreatment of rats with PB, ISO, and 3-MC reduced AUC(10-120 min) of THA in liver perfusates by 28, 32, and 86% respectively. 3. Elimination of [14C]-THA-derived radioactivity into bile was 7.6 +/- 1.2%, 11.7 +/- 2.9%, 14.8 +/- 2.0%, and 46.3 +/- 9.7% (mean +/- SD) of the infusion dose for control PB, ISO, and 3-MC pretreated isolated perfused rat livers, respectively. 4. In perfusion experiments using 3-MC pretreated livers, a marked increase in irreversible protein binding of 3-, 7-, and 8-fold was observed to microsomal, cytosolic and total liver proteins, respectively, compared to control. Only a slight effect was observed on protein binding in perfusion experiments using PB and ISO pretreated animals. 5. Co-incubations of [14C]-THA with the metabolic inhibitors enoxacin, ethimizol, and furafylline in hepatocyte preparations obtained from 3-MC pretreated rats markedly inhibited THA-derived irreversible protein binding. Furafylline, a specific inhibitor of cytochrome P4501A2, had the greatest inhibitory effect (approximately 70%). 6. These results are consistent with a major role of cytochrome P4501A in the metabolism and irreversible protein binding of THA in rat liver and demonstrate the utility of isolated liver perfusion and hepatocyte models for examining the effect of metabolic modulators.

Down-regulation of albumin synthesis in the rat by human recombinant interleukin-1 beta or turpentine and the response to nutrients.

Inflammatory stimuli and provision of nutrients are important factors regulating both total liver protein synthesis and albumin synthesis. The influence of interleukin-1 beta or turpentine injection and a 2-hour infusion of a hypocaloric mixture of glucose and amino acids on the synthesis of total liver protein and albumin was investigated in rats. Total liver protein synthesis was measured by an i.v. flooding dose of L-[2,6(3)H]phenylalanine and albumin synthesis was determined from the labeling of immunoprecipitated albumin and expressed both as a fraction of total liver protein synthesis and as an absolute rate. Interleukin-1 beta or turpentine injection stimulated total liver protein synthesis compared with controls, whereas albumin synthesis, both as a fraction of total liver protein synthesis and as an absolute synthesis rate, decreased. In control animals, the 2-hour i.v. infusion with glucose and amino acids resulted in a significant increase of total liver protein synthesis. Albumin synthesis as a fraction of total liver protein synthesis was not altered, but increased when expressed as an absolute rate in control animals. However, interleukin-1 beta or turpentine injection abolished this response of albumin synthesis to nutrient supply. Total liver protein synthesis increases under inflammatory conditions and remains responsive to nutrient supply. In contrast, albumin synthesis decreases under the same conditions and does not seem to be responsive to short-term i.v. nutrients.

Characterization of mechanisms causing hypoalbuminemia in rats with long-term bile duct ligation

Albumin kinetics and albumin synthesis were studied in rats with chronic bile duct ligation and compared with pair-fed control rats. The plasma albumin concentration was significantly reduced in bile duct ligated rats as compared to control rats, averaging 35±1 vs 40±2 g/l after 2 weeks and 28±3 vs 38±5 g/l after 4 weeks of bile duct ligation. Two weeks after the bile duct ligatio, the transcapillary escape rate of albumin was increased by 60% in bile duct ligated rats, whereas the plasma volume was unchanged. Albumin synthesis expressed as a fraction of total liver protein synthesis, as assessed by the ‘flooding’ dose method using [ 3H]phenylalanine, was decreased by 46% in bile duct ligated rats. However, absolute albumin synthesis expressed per 100 g body weight was not different from control rats. Four weeks after bile duct ligation, the transcapillary escape rate of albumin was no longer different, whereas the plasma volume was increased by 38% in bile duct ligated rats. At this time point, albumin synthesis as a fraction of total liver protein synthesis was decreased by 60% in bile duct ligated rats, and absolute albumin synthesis expressed per 100 g body weight averaged 80±8 vs 53±12 mg/(day×100 g) in control and bile duct ligated rats ( p<0.05). The hepatic steady-state levels of albumin mRNA determined by Northern blot analysis were decreased in bile duct ligated rats at both 2 and 4 weeks after surgery. The studies suggest that reduced plasma albumin concentrations in bile duct ligated rats are caused by increased capillary permeability and lack of compensatory increase in albumin synthesis 2 weeks, and by increased plasma volume and decreased albumin synthesis 4 weeks after surgery.

Growth, hormonal status and protein turnover in rats fed on a diet containing peas (Pisum sativum L.) as the source of protein.

The inclusion of peas (Pisum sativum L.) as the source of protein in the diet of growing rats brings about a reduction in growth rate as well as the impairment in the liver, muscle and spleen weights as compared with casein fed controls. Also, a fall in plasma glucose, triglycerides and protein was observed in the legume fed animals, while no changes in cholesterol levels were found. Furthermore, the rats fed on the diet containing peas showed lower levels of plasma insulin, corticosterone, IGF-I and T4 as compared with casein controls. Liver and muscle total protein (mg) and total DNA (mg) were markedly decreased in the legume fed animals, but DNA/g, protein/DNA and RNA/protein ratios were similar in both dietary groups. Likewise, liver and muscle fractional synthesis rates were similar in the casein and legume groups, while the whole body protein synthesis is assumed to be lower in the legume fed animals due to differences in body weights. It is concluded that animals fed on a diet containing peas (Pisum sativum L.) as the only source of protein showed less adverse effects than those found with other legumes such as Vicia faba L. or Phaseolus vulgaris L., in which protein quality, antinutritional factors and nutrient availability could be involved.

Enzyme-linked immunosorbent assay of carbamoylphosphate synthetase I: plasma enzyme in rat experimental hepatitis and its clearance.

Carbamoylphosphate synthetase I (CPS I), a urea cycle enzyme, is located almost exclusively in the mitochondria of hepatocytes. The enzyme is unique in that it constitutes about 2-6% of total liver protein and is composed of a large subunit of 160 kD. We developed a sensitive enzyme-linked immunosorbent assay (ELISA) for measurement of the enzyme in plasma using an antibody against the rat enzyme. In galactosamine-induced rat acute hepatitis, plasma concentration of CPS I that was 1-2 micrograms/ml blood before the treatment, increased up to 125 micrograms/ml blood in 24 h after the treatment and decreased to a near control level in 72 h. Plasma concentration of ornithine carbamoyl-transferase (OCT), another urea cycle enzyme, reached a maximum in 24 h and then decreased a little more rapidly than that of CPS I. On the other hand, alanine aminotransferase activity reached a maximum in 36 h and decreased to a normal level in 96 h. In immunoblot analysis, the native CPS I polypeptide of 160 kD and its fragments of 140 and 125 kD were detected 24-48 h after the treatment. When purified rat CPS I and bovine OCT were injected intravenously into rats, the enzymes disappeared from blood roughly exponentially with apparent half-lives of about 67 and 18 min, respectively. Development of an ELISA for human CPS I and determination of the serum enzyme in various liver diseases remain to be performed.

Use of the [14C]aminopyrine breath test to assess the hepatic response of dietary obese rats to a very-low-energy diet

The intake of a very-low-energy diet (VLED) complete in all essential nutrients decreases liver mass and total liver protein in dietary obese rats. To determine how these findings may affect hepatic drug metabolizing activity, the aminopyrine breath test was performed in nine male dietary obese Sprague-Dawley rats weighing 440-460 g. Animals were maintained on a VLED, and at 0, 14, and 21 d were injected with 9.25 k Bq (0.25 microCi) [dimethylamine-14C]aminopyrine and placed in airtight restraining cages; exhaled 14CO2 was collected for 120 min. VLED animals had an increased half-life of exhaled 14CO2 (P < 0.01) and a decreased rate constant of aminopyrine elimination (P < 0.01) consistent with decreased N-demethylation of aminopyrine. Decreased liver glutathione suggests reduced ability to detoxify drugs through this conjugation pathway. These studies suggest that animals on VLEDs have reduced capacity for demethylation of aminopyrine as measured by oxidative elimination of 14CO2, and may exhibit decreased metabolism of other drugs.

Chronic ethanol consumption induces accumulation of proteins in the liver Golgi apparatus and decreases galactosyltransferase activity.

The effect of chronic ethanol consumption on labeled glycoprotein secretion and galactosyltransferase activity has been analyzed in cis- and trans-Golgi apparatus fractions isolated from rat liver. Rats were injected intraperitoneally with 3H-leucine, after different chase periods (30, 60, 180 min), and the radioactivity of the different subcellular fractions as well as of the isolated Golgi apparatus was measured. Chronic alcohol treatment induces an increase in liver weight as well as an enhancement of total liver protein. Ethanol treatment produces a significant accumulation of labeled proteins in isolated Golgi apparatus fractions after a 60- and 180-min chase. An accumulation of labeled proteins in the cytosolic fraction was observed only after 180 min. The alcohol treatment also induces a significant decrease in the activity of galactosyltransferase in both liver homogenate and Golgi apparatus fractions. These results suggest that an impairment of Golgi apparatus functions, including glycosylation and glycoprotein trafficking, could be one of the mechanisms involved in the accumulation of hepatic protein and thus in the pathogenesis of alcohol-induced injury in the liver of chronic ethanol-consuming animals.

Alterations in Liver Composition of Channel Catfish (Ictalurus punctatus) during Seasonal Acclimatization

Compositional alterations in liver and heart in channel catfish during seasonal acclimatization were compared with patterns observed during temperature acclimation. Hepatosomatic index (HSI) was minimal in the summer (>25° C), highest in the spring and fall (12°-18° C), and intermediate in winter (4°-9° C). Alterations in heart (ventricle) mass were in the order winter > fall > summer and correlated with the pattern observed during acclimation. Liver protein content was relatively constant except in summer, when total liver protein was approximately half that of other seasons. Dietary insuficiency was indicated in summer animals by elevated tissue water content. Liver DNA, like HSI, showed maxima in fall and spring and minima in summer and winter. Liver RNA levels were lowest in the summer and highest in the spring. Protein/DNA and RNA/ DNA ratios increased from fall through winter to a maximum in the spring as a prelude to spawning but declined precipitously in the summer. Liver glycogen content, which was highest in the fall, was reduced during summer to values 13-fold lower than in the fall. Total lipid was highest in the spring and lowest in summer, primarily reflecting alterations in neutral lipid. Phospholipid showed little seasonal variation except in summer, when it was half that at other seasons, and this may reflect significant alterations in either subcellular organelles or hepatocyte numbers. Although temperature plays a major role in the observed alterations in tissue composition and often reflects a pattern similar to that observed for laboratory acclimation, other factors, particularly dietary deficiencies at seasonal temperature extremes, likely modify compositional patterns.

Chronic physical activity: Hepatic hypertrophy and increased total biotransformation enzyme activity

Does chronic voluntary physical activity alter hepatic or intestinal capacities for xenobiotic biotransformation? This question was investigated by comparing biotransformation enzyme activities in liver and small intestine of active and sedentary rats. Male rats allowed unlimited access to a running wheel and fed ad lib. for 6 weeks were weight-matched to sedentary controls; the active rats ate 22% more food than the sedentary rats (P < 0.05). Active rats ran 2.8 ± 0.6 miles/day. Liver weights were higher in the active rats (11.2 ± 0.2 vs 9.8 ± 0.2 g; P < 0.05), as were total liver protein, and liver microsomal and cytosolic protein (P < 0.05). As a result of liver hypertrophy, the active rats showed higher total liver activity of several biotransformation enzymes, including 2-naphthol sulfotransferase, styrene oxide hydrolase, benzphetamine N-demethylase, ethacrynic acid glutathione S-transferase and morphine UDP-glucuronosyltransferase (P < 0.05). In contrast, there was no detectable difference in total liver N-acetyltransferase activity toward p-aminobenzoic acid, 2-naphthylamine, and 2-aminofluorene as well as, relative hepatic enzyme activity (expressed per g liver or per mg protein) and total and relative intestinal enzyme activity. We conclude that chronic voluntary physical activity, accompanied by an increased food intake, results in liver hypertrophy and potentially increases total hepatic capacity to biotransform certain xenobiotic chemicals.