The effect of diet on carbon tetrachloride metabolism

1. Blood and liver concentrations of carbon tetrachloride were measured, at intervals after an oral dose, in rats given stock and protein-free diets. The values did not correlate with the resistance to poisoning found in the rats on protein-free diets. 2. The metabolism of carbon tetrachloride to carbon dioxide in vivo and in liver microsomal preparations was depressed in animals given protein-free diets. 3. Rats given a single dose of DDT [1,1,1-trichloro-2,2-bis-(p-chlorophenyl)ethane] were highly sensitive to carbon tetrachloride poisoning. The livers of such animals had an increased microsomal protein content and greatly increased microsomal activity in the demethylation of Pyramidon (aminopyrine) and in the conversion of ¹⁴CCl₄ into ¹⁴CO₂. 4. The incorporation of [¹⁴C]leucine into protein by liver slices was depressed by carbon tetrachloride. This effect was decreased by addition of SKF525A (2-diethylaminoethyl 2,2-diphenyl-2-propylacetate) and in slices from rats given protein-free diets. It is suggested that the toxicity of carbon tetrachloride is closely linked to its metabolism.     

Control of alanine metabolism in rat liver by transport processes or cellular metabolism.

1. Factors governing hepatic utilization of alanine were studied in vivo and in vitro in rats adapted to increasing dietary protein. 2. Hepatic alanine utilization was enhanced 5-fold with a 90%-casein diet, compared with a 13%-casein diet. The increased uptake resulted from enhanced fractional extraction in the presence of high concentrations of alanine in the portal vein. 3. The increase in alanine metabolism on high-protein diets was associated with an increase in alanine aminotransferase and in pyruvate utilization for gluconeogenesis. 4. The emergence of a high-affinity component appeared to be responsible for the enhanced transport of alanine with high-protein diets. 5. High extracellular concentrations after alanine loads resulted in a maximal rate of utilization and of accumulation of alanine by liver cells in vivo and in vitro. Alanine accumulation was particularly active with high-protein diets. 6. In starved rats, alanine transport was also increased, but low concentrations of alanine in afferent blood contributed to make transport limiting for alanine utilization. 7. In fed rats, the rates of transport and catabolism of alanine generally appear to undergo parallel changes; both processes thus play a fundamental role in the control of alanine utilization by the liver.     

Activities of fatty acid desaturases and fatty acid composition of liver microsomes in rats fed beta-carotene and 13-cis-retinoic acid

The fatty acid composition of microsomal lipids and the activities of delta 9- and delta 6-desaturases in liver microsomes of rats fed diets supplemented with beta-carotene and two levels of 13-cis-retinoic acid were studied. Four groups of male, weanling rats were fed semipurified diets containing 0 or 100 mg beta-carotene per kg diet, and 20 or 100 mg 13-cis-retinoic acid per kg diet. After 11 weeks of feeding, the rats were killed, liver microsomes were prepared and assayed for delta 9-desaturase and delta 6-desaturase activities. The activity of delta 9-desaturase was lower in liver microsomes of rats fed beta-carotene-supplemented diet or the diet supplemented with the higher level of 13-cis-retinoic acid. Microsomal delta 6-desaturase activity was, however, higher in liver of rats fed 13-cis retinoic acid; there was no effect of beta-carotene on delta 6-desaturase activity. The fatty acid compositional data on total lipids of liver microsomes were consistent with the diet-induced changes in fatty acid desaturases. Phospholipid composition of liver microsomes was also altered as a result of feeding beta-carotene or 13-cis-retinoic acid-containing diets. The proportions of phosphatidylethanolamine were generally higher, whereas those of phosphatidylcholine were lower in the experimental groups as compared with the control.     

A requirement for dietary lipids for induction of cytochrome P-450 by phenobarbitone in rat liver microsomal fraction

1. Rats fed on purified synthetic diets have a markedly lower cytochrome P-450 concentration and hydroxylating enzyme activity in liver microsomal fraction than rats fed on stock pellets. 2. When both groups are treated with phenobarbitone the difference is even greater, the purified diet allowing only 50% of the cytochrome P-450 concentrations of controls. 3. Addition of herring oil, linoleic acid or 0.1% oxidized sitosterol to the diets allows induction of cytochrome P-450 to take place. 4. Addition of coconut oil to the diet does not permit induction of cytochrome P-450. 5. The interactions between dietary protein and the lipid substances are explored. 6. The mechanism of induction of microsomal hydroxylation enzymes by drugs is discussed in the light of these requirements.     

A Freshwater Clam (Corbicula fluminea) Extract Improves Cholesterol Metabolism in Rats Fed on a High-Cholesterol Diet

The effect of a freshwater clam (Corbicula fluminea) extract (FCE) on cholesterol metabolism in rats fed on a high-cholesterol diet was investigated. When rats were fed various amounts of FCE in addition to the high-cholesterol diet for 2 wk, the serum and hepatic cholesterol levels were gradually reduced in a dose-dependent manner, as compared with the control group. The excretion of neutral sterols and bile acids into the feces was increased by feeding FCE. Several phytosterols were detected in the feces of rats fed on the FCE-containing diet. In addition, substantial amounts of phytosterols were found in FCE. Cholesterol 7α-hydroxylase (CYP7A1) mRNA in the liver of the rats fed on the FCE-containing diets was higher than that of rats fed on the high-cholesterol diets without FCE. These results may suggest that enhanced cholesterol degradation and the excretion of neutral sterols and bile acids contributed to the hypocholesterolemic effect of FCE observed in the hypercholesterolemic rats fed on the high-cholesterol diet.     

Effects of dietary carbohydrate and myo-inositol on metabolic changes in rats fed 1,1,1-trichloro-2,2-bis (p-chlorophenyl) ethane (DDT)

This study was conducted to examine the effects of dietary carbohydrate [starch or sucrose (500 g/kg diet)] and myo-inositol (2 g/kg diet) on metabolic changes in rats fed 1,1,1-trichloro-2,2-bis (p-chlorophenyl) ethane (DDT) (0.7 g/kg diet). Dietary DDT enhanced serum and hepatic lipids and hepatic thiobarbituric acid reactive substances (TBA-RS), elevated hepatic activities of lipogenic enzymes such as malic enzyme (ME), glucose-6-phosphate dehydrogenase (G6PD) and fatty acid synthetase (FAS), increased hepatic cytochrome P-450 content and the activities of drug-metabolizing enzymes such as aminopyrine N-demethylase, glutathione S-transferase and 4-nitrophenol-UDP glucuronosyltransferase (4NP-UDPGT) and raised hepatic ascorbic acid and serum copper. Dietary sucrose promoted the increases in hepatic concentrations of total lipids, triglyceride and cholesterol, hepatic activity of ME, hepatic TBA-RS, cytochrome P-450 content and serum copper due to DDT feeding when compared to DDT administered in a starch based diet. Dietary myo-inositol significantly depressed the rises in hepatic concentrations of total lipids, triglyceride and cholesterol and the activities of ME and G6PD due to DDT feeding regardless of dietary carbohydrate quality. Dietary starch supplemented with myo-inositol potentiated the enhancements in hepatic activities of Phase II drug-metabolizing enzymes such as glutathione S-transferase and 4NP-UDPGT due to DDT feeding. These results suggest that dietary starch and myo-inositol can protect DDT fed rats against an accumulation of hepatic lipids, which might be mainly ascribed to the depression of hepatic lipogenesis. In addition, the present study implies that the supplementation of myo-inositol to high starch diet might improve the function of drug-metabolizing enzymes exposed to DDT.     

A freshwater clam (Corbicula fluminea) extract improves cholesterol metabolism in rats fed on a high-cholesterol diet

The effect of a freshwater clam (Corbicula fluminea) extract (FCE) on cholesterol metabolism in rats fed on a high-cholesterol diet was investigated. When rats were fed various amounts of FCE in addition to the high-cholesterol diet for 2 wk, the serum and hepatic cholesterol levels were gradually reduced in a dose-dependent manner, as compared with the control group. The excretion of neutral sterols and bile acids into the feces was increased by feeding FCE. Several phytosterols were detected in the feces of rats fed on the FCE-containing diet. In addition, substantial amounts of phytosterols were found in FCE. Cholesterol 7alpha-hydroxylase (CYP7A1) mRNA in the liver of the rats fed on the FCE-containing diets was higher than that of rats fed on the high-cholesterol diets without FCE. These results may suggest that enhanced cholesterol degradation and the excretion of neutral sterols and bile acids contributed to the hypocholesterolemic effect of FCE observed in the hypercholesterolemic rats fed on the high-cholesterol diet.     

Effects of diet and of alloxan-diabetes on the activity of branched-chain 2-oxo acid dehydrogenase complex and of activator protein in rat tissues.

The total activities (sum of active and inactive forms) of branched-chain 2-oxo acid dehydrogenase complex in tissues of normal rats fed on a standard diet were (unit/g wet wt.): liver, 0.82; kidney, 0.77; heart, 0.57; hindlimb skeletal muscles, 0.034. Total activity was decreased in liver by 9%- or 0%-casein diets and by 48 h starvation, but not by alloxan-diabetes. Total activities were unchanged in kidney and heart. The amount of active form of the complex (in unit/g wet wt. and as % of total) in tissues of normal rats fed on standard diet was: liver, 0.45, 55%; kidney, 0.55, 71%; heart, 0.03, 5%; skeletal muscle less than 0.007, less than 20% (below lower limit of assay). The concentration of the active form of the complex was decreased in liver and kidney, but not in heart, by low-protein diets, 48 h starvation and alloxan-diabetes. In heart muscle alloxan-diabetes increased the concentration of active complex. The concentration of activator protein (which activates phosphorylated complex without dephosphorylation) in liver and kidney was decreased by 70-90% by low-protein diets and 48 h starvation. Alloxan-diabetes decreased activator protein in liver, but not in kidney. Evidence is given that in tissues of rats fed on a normal diet approx. 70% of whole-body active branched chain complex is in the liver and that the major change in activity occasioned by low-protein diets is also in the liver.     

Metabolic Effects of Arginine and Methionine Supplement on Rats Fed Excess Glycine Diets

The contents of glycogen, lipid, urea and amino acids, and some enzyme activities in plasma, liver muscle and urine were determined with rats fed 10 to 12 g of 100 g body weight per day of the 10% casein diet (control) and 10% casein diets containing 7% glycine with or without 1.4% l-arginine HC1 and l-methionine for 7 days.

Nine hours after the final feeding, the amount of liver glycogen was high in the order of rats fed 10% casein diet containing 7% glycine, 10% casein diet containing 7% glycine with l-arginine and l-methionine, and the control. The amount of muscle glycogen was decreased only in those fed the control diet. The amount of liver lipid was increased by the addition of l-arginine and l-methionine to the excess glycine diet. Plasma and urinary urea was increased in animals given the excess glycine diets with or without both amino acids. In plasma liver, and muscle of animals given either of both the excess glycine diets 3 and 9 hr after the feeding, in general, glycine and serine were increased, and threonine and alanine were decreased as compared with those of rats given the control diet. However, the increase of glycine in plasma, liver and muscle detected at 9 hr after feeding the excess glycine diet was slightly prevented by the supplementation of both amino acids to the excess glycine diet. The activities of liver glycine oxidase and ornithine δ-aminotransferase of rats given the excess glycine diet with both amino acids were higher than those of other dietary groups. Liver serine dehydratase and glutamate-oxalacetate transaminase activities were high in the order of the animals fed the control, the excess glycine diet and the excess glycine diet containing both amino acids. Glutamate-pyruvate transaminase activity in the liver of rats fed the excess glycine diets with or without both amino acids were markedly higher than that of those fed the control. The activities of phosphopyruvate carboxylase and aconitase in the liver of animals given the excess glycine diet were higher than those of other dietary groups. Liver pyruvate kinase and glutamate dehydrogenase activities were similar among those dietary groups.     

Influence of dietary fat on the lipid composition of rat brain synaptosomal and microsomal membranes.

The modulation of rat brain microsomal and synaptosomal membrane lipid by diet fat was examined. Brain synaptosomal and microsomal membrane composition was compared for rats fed on diets containing either soya-bean oil (SBO), SBO plus choline, SBO lecithin, sunflower oil (SFO), chow or low-erucic acid rape-seed oil (LER) for 24 days. Cholesterol and phosphatidylcholine levels in both membranes were altered by diet. Diet fat also affected the microsomal content of sphingomyelin. Change in membrane phosphatidylcholine level was related to the relative balance of omega-6, omega-3 and monounsaturated fatty acids within the diets fed. The highest phosphatidylcholine levels appeared in membranes of animals fed on SBO lecithin and the lowest in those fed on LER. Microsomal membrane cholesterol and sphingomyelin content increased by feeding on SBO lecithin. In both synaptosomal and microsomal membranes a highly significant correlation was observed between membrane phosphatidylcholine and cholesterol content. The fatty acyl composition of phospholipids from both membranes also altered with diet and age. Alteration in fatty acid composition was observed in response to dietary levels of omega-6, omega-3 and monounsaturated fatty acids, but the unsaturation index of each phospholipid remained constant for all diet treatments. These changes in lipid composition suggest that dietary fat may be a significant modulator in vivo of the physicobiochemical properties of brain synaptosomal and microsomal membranes.     

The role of lipid components of the diet in the regulation of the fatty acid composition of the rat liver endoplasmic reticulum and lipid peroxidation

The fatty acid compositions of the lipids and the lipid peroxide concentrations and rates of lipid peroxidation were determined in suspensions of liver endoplasmic reticulum isolated from rats fed on synthetic diets in which the fatty acid composition had been varied but the remaining constituents (protein, carbohydrate, vitamins and minerals) kept constant. Stock diet and synthetic diets containing no fat, 10% corn oil, herring oil, coconut oil or lard were used. The fatty acid composition of the liver endoplasmic reticulum lipid was markedly dependent on the fatty acid composition of the dietary lipid. Feeding a herring-oil diet caused incorporation of 8.7% eicosapentaenoic acid (C_20:5) and 17% docosahexaenoic acid (C_22:6), but only 5.1% linoleic acid (C_18:2) and 6.4% arachidonic acid (C_20:4), feeding a corn-oil diet caused incorporation of 25.1% C_18:2, 17.8% C_20:4 and 2.5% C_22:6 fatty acids, and feeding a lard diet caused incorporation of 10.3% C_18:2, 13.5% C_20:4 and 4.3% C_22:6 fatty acids into the liver endoplasmic-reticulum lipids. Phenobarbitone injection (100mg/kg) decreased the incorporation of C_20:4 and C_22:6 fatty acids into the liver endoplasmic reticulum of rats fed on a lard, corn-oil or herring-oil diet. Microsomal lipid peroxide concentrations and rates of peroxidation in the presence of ascorbate depended on the nature and quantity of the polyunsaturated fatty acids in the diet. The lipid peroxide content was 1.82±0.30nmol of malonaldehyde/mg of protein and the rate of peroxidation was 0.60±0.08nmol of malonaldehyde/min per mg of protein after feeding a fat-free diet, and the values were increased to 20.80nmol of malonaldehyde/mg of protein and 3.73nmol of malonaldehyde/min per mg of protein after feeding a 10% herring-oil diet in which polyunsaturated fatty acids formed 24% of the total fatty acids. Addition of α-tocopherol to the diets (120mg/kg of diet) caused a very large decrease in the lipid peroxide concentration and rate of lipid peroxidation in the endoplasmic reticulum, but addition of the synthetic anti-oxidant 2,6-di-t-butyl-4-methylphenol to the diet (100mg/kg of diet) was ineffective. Treatment of the animals with phenobarbitone (1mg/ml of drinking water) caused a sharp fall in the rate of lipid peroxidation. It is concluded that the polyunsaturated fatty acid composition of the diet regulates the fatty acid composition of the liver endoplasmic reticulum, and this in turn is an important factor controlling the rate and extent of lipid peroxidation in vitro and possibly in vivo.     

Metabolism of amino acids in protein-calorie-deficient rats

The overall oxidative degradation of leucine and phenylalanine, measured in vivo in rats fed on a 2%-casein diet for 8 weeks, is markedly decreased as compared with controls, whereas that of glutamate and alanine is apparently unaffected. The decrease in leucine degradation is due, at least in part, to a block before the formation of 3-methylbutyryl-CoA (isovaleryl-CoA) in the catabolic pathway. This phenomenon is accompanied by increased incorporation of [¹⁴C]leucine into liver proteins, decreased urinary excretion of leucine and increased urinary excretion of 4-methyl-2-oxopentanoate (α-oxoisocaproate) by protein-depleted animals. The results suggest the existence of adaptive mechanisms that function to conserve an indispensable carbon skeleton.     

Effects of chronic modification of dietary fat and carbohydrate on the insulin, corticosterone and metabolic responses of rats fed acutely with glucose, fructose or ethanol

1. Male rats were fed for 14 days on powdered diets containing (by weight) 53% of starch, or on diets in which 20g of starch per 100g of diet was replaced by lard or corn oil. They were then fed acutely by stomach tube with a single dose of glucose, fructose or ethanol of equivalent energy contents, or with 0.15m-NaCl. The serum concentrations of corticosterone, insulin, glucose, glycerol, triacylglycerol and cholesterol were measured up to 6h after this treatment. 2. Feeding saline (0.9% NaCl) acutely to the rats maintained on the three powdered diets produced a small transient increase in circulating corticosterone that was similar to that in rats maintained on the normal 41B pelleted diet. 3. Feeding glucose acutely to the rats on the powdered diets produced peak concentrations of corticosterone that were 2–3-fold higher than those seen in rats maintained on the 41B diet. The duration of this response increased in the order starch diet<lard diet<corn-oil diet. This abnormal corticosterone response to glucose feeding appeared to be responsible for an increased activity in phosphatidate phosphohydrolase in the livers of rats fed the starch and lard diets of 2.9- and 4.9-fold respectively. The latter increase was similar to that produced by ethanol, whereas glucose did not increase the phosphohydrolase activity in the liver of rats maintained on the 41B diet. 4. Feeding fructose acutely produced even more marked increases than glucose in the concentrations of circulating corticosterone in rats given the powdered diets, but unlike glucose did not increase circulating insulin. The duration of the corticosterone response again increased in the order starch diet<lard diet<corn-oil diet. The concentrations of circulating glucose were increased by fructose feeding in rats maintained on these diets, but they were not altered in the rats maintained on the 41B pellets. A prolonged increase in serum corticosterone concentrations was also observed when fructose was fed to rats maintained on pelleted diets enriched with corn oil or beef tallow rather than with starch or sucrose. However, these effects were less marked than those seen with rats fed on the powdered diets. 5. These results are discussed in relation to the mechanism whereby high dietary fat exaggerates the effects of ethanol, fructose and sorbitol in stimulating triacylglycerol synthesis in the liver.     

Effect of long-term feeding olive and sunflower oils on fatty acid composition and desaturation activities of liver microsomes

Changes in microsomal fatty acid composition, delta 9- and delta 6-desaturase activities and cholesterol and phosphorus liver content were studied in dogs fed olive and sunflower oil diets. No changes were observed in the saturated fatty acids between dietary groups. The level of monounsaturated fatty acids was more elevated in animals fed the OO diet, because of its high relative content in this diet although the in vitro delta 9-desaturase activity was similar in microsomes from the two groups. The proportion of arachidonic acid was similar in SO and OO fed animals. This similar level occurred despite a significant increase in the level of linoleic acid in membrane lipids as a result of feeding the SO supplement. The in vitro delta 6-desaturase activity in liver microsomes showed no differences between dogs fed the two diets. Thus, the higher desaturation presented in vivo by microsomes from OO group may be related to the inhibition by linoleic acid of delta 6-desaturase in dogs fed the SO diet. The polyunsaturated fatty acids (PUFA) from the n-3 series were higher in microsomal phosphatidylcholine and phosphatidylethanolamine from animals fed the OO supplemented diet. The cholesterol/phosphorus molar ratio was higher in the SO group in which the unsaturation index was only slightly affected in phospholipids.     

Dietary fat and cholesterol induced modification of minipig lipoprotein fluidity and composition.

1. Miniature swine were fed a low (2.7%) fat control stock diet alone or supplemented with either 20% lard plus 1% cholesterol or 20% lard alone for periods of up to 6 months. 2. Cholesterol feeding reduced VLDL fluidity drastically and LDL fluidity minimally but had no effect on HDL fluidity. 3. Lard feeding had no effect on lipoprotein fluidity. 4. The rigid VLDL produced by cholesterol feeding was enriched in cholesterol and phospholipid contents, similar to beta-VLDL. 5. Plasma cholesterol concentrations were increased by 1.5 to 5-fold in pigs fed stock diets supplemented with 20% lard, with or without added cholesterol, but plasma triacylglycerol concentrations were not affected by either diet modification. 6. Diet effects were complete within 4 weeks with no further changes for periods up to 6 months. 7. Regression of the induced hypercholesterolemia was also accomplished within one month of removing cholesterol from the diet.     

Effects of dietary protein of proso millet on liver injury induced by D-galactosamine in rats

In this paper, we examined the effects of dietary protein from proso millet on liver injury induced by D-galactosamine or carbon tetrachloride in rats using serum enzyme activities as indices. D-galactosamine-induced elevations of serum activities of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase were significantly suppressed by feeding the diet containing 20% protein of proso millet for 14 days as compared with those of rats fed a 20% casein diet, but not in the case of carbon tetrachloride. The results showed that proso millet protein is effective at lower dietary protein levels than that of dietary gluten reported previously. Therefore, the findings reported here may suggest that proso millet protein is considered to be another preventive food for liver injury.     

Effects of Feeding a Histidine-excess Diet and Subsequent Starvation on Liver and Muscle Glycogen,and on Serum Glucose

The effects of feeding with a histidine-excess diet and subsequent starvation on liver and muscle glycogen, and on serum glucose were investigated in young and adult rats.

Feeding with a histidine-excess diet resulted in the accumulation of liver glycogen in both young and adult rats. The hepatic glycogen continued to decrease during starvation, and the liver became almost totally depleted of glycogen after starvation for 48 hr. Glycogen in the liver of young rats starved for 24 hr after previous feeding with a histidine-excess diet was significantly higher than that of young rats starved for 24 hr after previous feeding with a basal diet.

Muscle glycogen after feeding and subsequent starvation was not affected by the types of diets fed previously, muscle glycogen during starvation showing a slight decrease in young rats and a slight increase in adult rats.

Feeding with a histidine-excess diet caused a significant decrease of serum glucose in young rats, but not in adult rats. Serum glucose in young rats was markedly reduced by starvation after previous feeding with a basal diet, but not after previous feeding with a histidine-excess diet. In adult rats, there were no changes in serum glucose between rats starved after feeding with either a basal diet or a histidine-excess diet, and serum glucose was decreased slightly by starvation after feeding with the test diets.

The overall results indicate that the maintenance of serum glucose in young rate even during starvation after previous feeding with a histidine-excess diet might be partially concerned with the export of glucose from the accumulated glycogen in the liver due to the diet.     

Effects of dietary oyster extract on lipid metabolism, blood pressure, and blood glucose in SD rats, hypertensive rats, and diabetic rats

Oyster extract was prepared by hydrolysis of oyster protein with proteases, Aloase (a protease from Bacillus subtilis), and Pancitase (a protease from Aspergillus oryzae). Rats were fed a diet containing 20% casein (the control diet) or 15% casein and 5% oyster extract (the oyster extract diet) as the protein source. The oyster extract diet exerted a significant reduction in serum cholesterol and liver triglyceride concentrations as compared with the control diet in Sprague-Dawley (SD) rats fed cholesterol-supplemented diets for 4 weeks. The activities of cytosolic fatty acid synthase and glucose-6-phosphate dehydrogenase were significantly lower in the oyster extract group than in the control group in the liver of SD rats. Hepatic cholesterol and triglyceride concentrations were significantly lower in spontaneously hypertensive (SH) rats and Otsuka Long-Evans Tokushima Fatty (OLETF) rats, type 2 diabetic rats, fed the oyster extract diet, for 4 weeks and 4 months respectively, than in those fed the control diet in the cholesterol-free diet. Blood pressure was significantly lower in the oyster extract group than in the control group at the 2nd and 4th weeks after the beginning of feeding experimental diets in SH rats. These results suggest that oyster extract prepared by hydrolysis of oyster induces triglyceride-lowering activity in the liver through a decrease in hepatic lipogenesis in SD rats, and that it exerts the antihypertensive effect in SH rats.     

Tryptophan Metabolism of Rats Fed on an Amino Acid Diet Devoid of One Branched Chain Amino Acid

In an attempt to study on metabolic changes in rats fed on an amino acid diet devoid of one branched chain amino acid and of niacin, rats were force-fed a leucine-free, isoleucine-free, valine-free or complete amino acid diet for 3 or 4 days and killed 3 hr after the feeding on day 4 or 5 to observe the body weight changes, the urinary nitrogen and N¹-methylnicotinamide (MNA), and liver tryptophanpyrrolase (TPase) and tyrosine-α-keto-glutarate transaminase (TKase) activities.

The excretion of the urinary nitrogen and MNA, TPase and TKase activities, and fat content of livers of rats force-fed these amino acid deficient diets were higher than those fed the complete amino acid diet. It was further confirmed in the present study that changes in TPase activity of rats given diets devoid of one essential amino acid were in the same direction with changes in urinary MNA which was observed in the previous studies on rats given threonine-free, tryptophan-free, methionine-free, lysine-free and complete amino acid diets. However, such metabolic changes in rats fed the leucine-free diet were not so remarkable, compared with those of rats fed the other amino acid deficient diets.     

Improvement of Hyperlipidemia and Proteinuria without Noticeable Growth Retardation by Feeding a Methionine and Threonine Supplemented Low-casein Diet to Nephritic Rats

We have previously demonstrated that low-casein diets supplemented with cystine and threonine reduced hyperlipidemia and proteinuria in nephritic rats without noticeable protein malnutrition. In the present study, we examined whether or not a low-casein diet supplemented with methionine, sulfur amino acid other than cystine, and threonine would ameliorate the symptoms without protein malnutrition in rats with nephrotoxic serum nephritis by feeding experimental diets for 10 days. A methionine-threonine-supplemented 8.5% casein diet (8.5 CMT), when compared with a basal 20% casein diet, improved hypoalbuminemia as well as hyperlipidemia and proteinuria without noticeable growth retardation and fatty liver induction in nephritic rats. Fecal bile acid excretion and microsomal cholesterol 7α-hydroxylase activity were enhanced by 8.5CMT feeding. These results suggest that amino acid-balanced low protein diet would have a beneficial effect on the symptoms of nephritis. They also suggest that the hypocholesterolemic action of 8.5CMT may be, at least in part, due to increased fecal bile acid excretion accompanied by elevated microsomal cholesterol 7α-hydroxylase activity.