Ascorbic acid deficiency induces hepatic and intestinal expression of inflammation-related genes irrespective of the presence or absence of gut microbiota in ODS rats

We have previously demonstrated that ascorbic acid (AsA) deficiency causes inflammatory changes in the liver and intestine in Osteogenic Disorder Shionogi (ODS) rats, which are unable to synthesize AsA. We have suggested that AsA deficiency increased intestinal interleukine (IL)-6 production, stimulating hepatic acute phase proteins (APPs) expression via the portal vein. In this study, we determined whether these hepatic and intestinal inflammatory changes by AsA deficiency are induced in germ-free (GF) ODS rats. For 18 days, male specific pathogen-free (SPF) ODS rats were fed the basal diet containing 600 mg AsA/kg (control group) or the AsA-free diet (AsA-deficient group) in SPF conditions, while male GF ODS rats were fed the basal diet (control group) or the AsA-free diet (AsA-deficient group) in GF conditions. Firstly, AsA deficiency significantly elevated the hepatic expression of APPs in both SPF and GF rats. In hepatic mRNA levels of some APPs, significant interaction between GF and AsA-deficiency effects was observed. Secondly, AsA deficiency elevated intestinal IL-6 and IL-1β mRNA levels in both SPF and GF rats, and significant interaction between GF and AsA-deficiency effects was observed in these mRNA levels of jejunum and cecum. In SPF and GF rats, AsA deficiency elevated portal IL-6 concentration. These results show that AsA deficiency caused hepatic and intestinal inflammatory changes in both the GF and SPF ODS rats and indicate that AsA deficiency could directly induce intestinal inflammatory changes without the involvement of gut microbiota.     

Environmental temperature and choline requirements in rats. II. Choline and methionine requirements for lipotropic activity

Young rats were fed choline-deficient diets and maintained at different environmental temperatures. The hepatic lipid level remained normal in rats at 2 degrees when 25 mg of choline per 100 g of food was fed; 50 mg of choline per 100 g food was required at 21 degrees and 100 mg of choline per 100 g food at 33 degrees to prevent excessive lipid accumulation. These values were equivalent to a mean daily intake per rat of 3 mg of choline at 2 degrees, 5.5 mg at 21 degrees, and 7 mg at 33 degrees respectively. When the growth rate was slower owing to a slight inadequacy of histidine in the basal choline-deficient diet, normal hepatic lipid was maintained by supplements of 50 mg of choline per 100 g food at 21 degrees and 33 degrees. Increasing the methionine content of the diet two- or three-fold from a basal value of 340 mg per 100 g food was as effective as 200 mg of choline per 100 g of food in lowering hepatic lipids at 2 degrees, 21 degrees, and 33 degrees.     

Effect of methotrexate on long-chain fatty acid metabolism in liver of rats fed a standard or a defined, choline-deficient diet

The effect of methotrexate on lipids in serum and liver and key enzymes involved in esterification and oxidation of long-chain fatty acids were investigated in rats fed a standard diet and a defined choline-deficient diet. Hepatic metabolism of long-chain fatty acids were also studied in rats fed the defined diet with or without choline. When methotrexate was administered to the rats fed the standard diet there was a slight increase in hepatic lipids and a moderate reduction in the serum level. The palmitoyl-CoA synthetase activity and the microsomal glycerophosphate acyltransferase activity in the liver of rats were increased by methotrexate. The data are consistent with those where the liver may fail to transfer the newly formed triacylglycerols into the plasma with a resultant increase in liver triacylglycerol content and a decrease in serum lipid levels. Fatty liver of methotrexate-exposed rats can not be attributed simply to a reduction of fatty acid oxidation as the carnitine palmitoyltransferase activity was increased. The methotrexate response in the rats fed the defined choline-deficient diet was different. There was a reduction in both serum and hepatic triacylglycerol and the glycerophosphate acyltransferase and palmitoyl-CoA synthetase activities. The carnitine palmitoyltransferase activity was unchanged. Hepatomegaly and increased hepatic fat content, but decreased serum triacylglycerol, total cholesterol and HDL cholesterol were found to be related to the development of choline deficiency as the pleiotropic responses were almost fully prevented by addition of choline to the choline-deficient diet. Addition of choline to the choline-deficient diet normalized the total palmitoyl-CoA synthetase and carnitine palmitoyltransferase activities. In contrast to methotrexate exposure, choline deficiency increased the mitochondrial glycerophosphate acyltransferase activity. The data are consistent with those of where fatty liver induction of choline deficiency may be related to an enhanced esterification of long-chain fatty acids concomitant with a reduction of their oxidation.     

Suppressive effect of excess dietary histidine on the expression of hepatic metallothionein-1 in rats

The gene expression of liver metallothionein-1 in excess dietary histidine was investigated by feeding rats ad libitum on either a basal or histidine-excess (50 g of L-histidine per kg of diet) diet for 5 d. The copper content of the liver and zinc level in the serum of the rats fed on the histidine-excess diet were lower by 21% and 61%, respectively of the figures for the rats fed on the basal diet, but the zinc content of the liver and copper level in the serum were not affected. Excess dietary histidine caused an increase in the urinary output of both copper and zinc. The level of liver metallothionine-1 mRNA was markedly lower at 19% in the rats fed on the a histidine-excess diet compared to the level with the basal diet. It thus appears that such a response by the level of liver metallothionein-1 mRNA might have been be due to the lower content of liver copper.     

Experimental oxalate urolith formation in rats.

Urinary calculi composed of calcium oxalate were produced in male hooded Wistar rats fed a vitamin B6 deficient diet over 16 weeks. This basic diet was modified by doubling the phosphate content or loading with vitamin C or D3 in three treatment groups. The number of rats developing oxalate stones was not altered by the addition of vitamin D3 or phosphate, but there was a significant increase in total weight of stone formed and histological evidence of extensive renal damage in rats on the high vitamin D3 diet. The addition of vitamin C to the vitamin B6 deficient rats resulted in a reduction in the number of rats with uroliths and a fall in urinary oxalate excretion, while similarly loaded vitamin B6 supplemented controls were free of oxalate calculi. It is concluded that the oxalate urolithiasis induced by vitamin B6 deficiency was exacerbated by added vitamin D3 and reduced by vitamin C.     

Effects of a methyl-deficient diet on rat liver phosphatidylcholine biosynthesis

To produce a severe choline-methionine deficiency, a synthetic L-amino acid diet, free of choline, methionine, vitamin B12, and folic acid and supplemented with guanidoacetic acid, a methyl group acceptor, was fed to female rats for 2 weeks. The in vitro activity of liver microsomal phosphatidylethanolamine methyltransferase was stimulated twofold when compared with basal diet controls. The activity of choline phosphotransferase was depressed by 86%; thus, the contribution of the methyltransferase in the overall synthesis of phosphatidylcholine apparently increased. However, measurement of the in vivo methylation of phosphatidylethanolamine by incorporation of [1,2-14C]ethanolamine into phosphatidylcholine indicates that the methylation pathway is markedly depressed in methyl deficiency. Hepatic concentrations of the methyltransferase substrate, S-adenosylmethionine, and the inhibitory metabolite, S-adenosylhomocysteine, were significantly altered such that an unfavorable environment for methylation was present in the deficient animal. The ratio of substrate to inhibitor was depressed from 5.2:1 in the controls to 1.7:1 in the livers of methyl-depleted rats. Control of transmethylation in accordance with the availability of substrates, phosphatidylethanolamine, or S-adenosylmethionine, and the level of S-adenosylhomocysteine is discussed.     

Learning is improved by a soybean oil diet in rats

A semi-synthetic diet containing 20% polyunsaturated fat (soybean) oil was fed to young male hooded rats for 21 days. These animals exhibited improved performance on an environmentally-cued testing paradigm which is thought to reflect cognitive learning skills (i.e., Place Navigation Water Task). Other rats fed the same base diet but containing 20% saturated fat (lard) showed no such improvement compared to chow-fed (4.5% mixed fat) controls. The animals fed soybean oil also exhibited a transient resistance to extinguish this learning. This improved learning could not be explained by changes in general motor activity, basal body temperature, energy consumption, body weight, or in the brain activity of choline acetyltransferase, the marker enzyme for cholinergic neurons. These findings constitute the first evidence that short-term variations in the quality of dietary fat can enhance mammalian learning.     

Effects of a new hypoglycemic agent A-4166 on glucose metabolism in rat adipocytes and muscle tissues

The effects of the oral administration of a non-sulfonylurea hypoglycemic agent, the phenylalanine derivative A-4166, on serum insulin and glucose levels and glucose metabolism in isolated rat adipocytes and slices of muscle tissues were studied. An increase in serum insulin and a decrease in glucose levels were observed 30 minutes after A-4166 administration to rats fed basal or high fat diet. No changes in basal glucose transport in isolated fat cells were observed after the administration of A-4166. The effect of in vitro added insulin was, however, stronger in rats fed basal diet and treated with A-4166. An elevation of the membrane glucose transporter GLUT 4 was observed in rats treated with A-4166. An increase of basal lipogenesis, measured by incorporation of radiocarbon labeled glucose into lipids, was noted in adipocytes from rats fed high fat diet. The addition of insulin was followed by stimulation of lipogenesis in rats fed basal diet, however, this hormone had no effect in rats fed high fat diet. The administration of A-4166 did not affect the basal or insulin stimulated lipogenesis. Basal glucose oxidation in the diaphragm was not influenced by high fat diet or by A-4166 treatment. In the soleus muscle, basal glucose oxidation was decreased in rats fed high fat diet, and treatment with A-4166 increased the glucose oxidation up to values observed in the control basal diet fed rats. These results indicate that the administration of A-4166 can affect glucose metabolism in muscle tissue and the sensitivity of adipocytes to insulin.     

Effects of diet and exposure to hindlimb suspension on estrous cycling in Sprague-Dawley rats

Various factors can disrupt the female reproductive cycle resulting in subfertility. The primary objective of this study was to determine whether physiological changes associated with exposure to hypogravity disrupt reproductive cycles. The hindlimb suspension (HLS) model was used to simulate the major physiological effects of hypogravity in female Sprague-Dawley rats. Also, to determine whether diet may influence reproductive results, rats were fed purified American Institute of Nutrition (AIN)-93G or chow diet. Rats (n = 9-11/group) subjected to HLS had lengthened estrous cycles due to prolonged diestrus, indicating hypoestrogenism. Interestingly, HLS rats fed AIN-93G but not chow diet had significantly reduced time spent in estrus and decreased plasma estradiol. Attenuation of hypoestrogenism in the chow-fed rats suggested that diet provided an exogenous source of estrogen. The mechanism involved in the disruption of estrous cycling remains to be determined. HLS increased urinary corticosterone (CORT) levels during the initial 4 days of HLS, suggesting that physiological responses to acute stress may be a potential mechanism in the disruption of estrous cycles. Higher basal urinary CORT was observed in rats fed chow vs. AIN-93G diet. HLS resulted in increased urinary CORT. However, two-way ANOVA indicated a significant HLS effect (P < 0.001) but no effect of HLS x diet effect on urinary CORT levels, suggesting that estrogenic activity associated with the chow diet did not enhance the stress response. The results of this study indicate that HLS, diet, and the combination of HLS and diet influence estrous cycling. This has important implications for future reproductive success in the hypogravity environment of space.     

Hepatic Subcellular Fractions Lipids in Rats Fed Millet (Sorghum vulgarie) at Different Protein Levels

Effect of feeding defatted millet (Sorghum vulgarie) flour at 5, 10 and 14.5% protein levels respectively for six weeks has been studied on rat liver mitochondrial, microsomal and supernatant fractions total lipids, cholesterol, triglycerides, total phospholipids, phosphatidyl choline and phosphatidyl ethanolamine. The results have been compared with rats fed casein at 10% level for the same period. The metabolism of liver subcellular fractions lipids of millet diet and casein diet fed rats has been studied by the incorporation of acetate-1-¹⁴C and . A significant increase in mitochondrial triglycerides of rats fed millet diet at 5 and 10% protein level, in microsomes of rats fed millet diet at 5, 10 and 15% protein levels and in supernatant fractions of rats fed millet diet at 5 and 15% protein levels was observed. A significant increase in total cholesterol in mitochondria and microsomes and a significant decrease in supernatant fraction of rats fed millet diet at 10% protein level was observed. A significant increase in mitochondrial total phospholipids, phosphatidyl choline and phosphatidyl ethanolamine in rats fed millet diet at 10% protein level and a decrease in these in rats fed millet diet at 5 per cent protein level was observed. In microsomes total phospholipids were increased in rats millet diet at 10% protein level and phosphatidyl choline was increased in rats fed millet diet at 15% protein level. Total phospholipids, phosphatidyl choline and phosphatidyl ethanolamine were significantly reduced in the supernatant fraction of rats fed millet at 10% protein level.

Incorporation of acetate-1-¹⁴C into nonsaponifiable fraction of mitochondria, microsomes and supernatant fractions of rats fed millet diet at 5 and 15 % protein levels was significantly greater, and in saponifiable fractions of the above subcellular fractions was greater in rats fed millet diet at 5 per cent protein level. The specific activity (counts/min/mg) of free cholesterol in mitochondria, microsomes and supernatant fractions of millet diet fed rats was significantly greater, whereas the specific activity of triglycerides was not significantly different from the controls. The acetate-1-¹⁴C specific activity of phosphatidyl choline and phosphatidyl ethanolamine was significantly greater in all the above subcellular fractions of millet diet fed rats (except of phosphatidyl choline in rats fed millet diet at 5 % protein level). The specific activities of phosphatidyl choline were significantly greater in mitochondria of rats fed millet diet at 5 % protein level and of phosphatidyl choline and phosphatidyl ethanolamine in microsomes and supernatant fractions of rats fed millet diet at 5 and 15% protein levels. The specific activities of phosphatidyl choline were significantly decreased in mitochondria and microsomes of rats fed millet diet at 10% protein level. The total acetate-1-¹⁴C activities (counts/min/g equivalent wet liver) of free and esterified cholesterol triglycerides, phosphatidyl choline and phosphatidyl ethanolamine showed that their synthesis from acetate-1-¹⁴C was either enhanced in millet diet fed rats or was comparable to the controls. The total activity of (counts/min/g equivalent wet liver) into phosphatidyl choline and phosphatidyl ethanolamine showed that their synthesis was decreased in microsomes of rats fed millet diet at 10% protein level, increased in rats fed millet diet at 5 and 15% protein levels.     

Urinary calculi in Lewis and Wistar rats

A high incidence (8/892) of urinary tract calculi was encountered during a study involving rats being fed diets supplemented with retinoids. When the incidence was compared to that observed in earlier studies without retinoid supplements and spanning several years (2/2998), the incidence in the current study was significantly higher. Possible causative factors such as age, sex, strain, diet and carcinogen or retinoid treatment have been analyzed without a clear explanation for the increased incidence. The data suggest that retinoid treatment increased the risk of stone formation, but that retinoids were less important than some other unidentified factor(s) that operated during the recent period.     

Choline and betaine ameliorate liver lipid accumulation induced by vitamin B6 deficiency in rats

We investigated the efficacy of supplementing the diet with choline or betaine in ameliorating lipid accumulation induced by vitamin B₆ (B₆) deficiency in rat liver. Male Wistar rats were fed a control, B₆-deficient, choline-supplemented (2, 4, or 6 g choline bitartrate/kg diet) B₆-deficient diet or betaine-supplemented (1, 2, or 4 g betaine anhydrous/kg diet) B₆-deficient diet for 35 d; all diets contained 9 g L-methionine (Met)/kg diet. Choline or betaine supplementation attenuated liver lipid deposition and restored plasma lipid profiles to control levels. These treatments restored the disruptions in Met metabolism and the phosphatidylcholine (PC)/phosphatidylethanolamine (PE) ratio induced by B₆ deficiency in liver microsomes. These results suggest that choline and betaine ameliorated liver lipid accumulation induced by B₆ deficiency via recovery of Met metabolism and very low-density lipoprotein secretion by restoring the supply of PC derived from PE.     

Free Radicals and Lipid Peroxidation in Liver of Rats Kept on a Diet Devoid of Choline

Rodents kept on a choline devoid (CD) diet up to 14 months develop hepatic lesions progressing through two broad stages. The first is chracterized by severe steatosis and increase in cell turnover, the second by a gradual clearance of the deposited fat and fibrosis. Hepatocellular carcinomas eventually arise in rats fed for over 12 months, even though the animals aer not exposed to chemical carcinogens. It has been suggested that the diet may trigger generated thereby may be responsible for intiation of liver cancer and promotion. The radicals would lead to DNA damage, and the altered DNA in a proliferating liver would result in initiation of the carcinogenic process. In this communication we present evidence that the diet used in the above studies contained stable fatty acid isomers with conjugated dienes, which are absorbed and deposited in rat liver. This finding cast doubts on whether a CD diet does indeed cause a peroxidation of cellular membrane lipids. Electron spin resonance (ESR) spectroscopy was also used to investigate whether any abnormal pattern of free radicals exists in the liver of rats fed a CD diet. No significant differences were noted in ESR spectra of either transition metal-centered signals, or organic free radicals.     

Effects of gender on kidney function in magnesium-deficient rats

This study investigated the gender differences in the kidney function of magnesium (Mg)-deficient rats. Male and female rats were fed a control diet or a Mg-deficient diet for 21 d. Mg-deficient diet had no significant effect on kidney calcium (Ca) or phosphorus (P) concentration in male rats, while Ca and P concentrations in female rats were significantly higher in Mg-deficient rats than in the control rats. With regard to indicators of kidney function, no significant differences in creatinine clearance and serum urea nitrogen concentration were observed among the groups. Serum albumin concentrations were significantly lower in rats fed the Mg-deficient diet than in rats fed the control diet. In both sexes, urinary albumin excretion was significantly higher in rats fed the Mg-deficient diet than in rats fed the control diet. Gender differences had no significant influence on creatinine clearance, serum urea nitrogen concentration, serum albumin concentration and urinary albumin excretion. These results suggest that gender differences have no effect on kidney function in Mg-deficient rats under the condition used.     

Influence of dietary methionine level on the liver metallothionein mRNA level in rats

The effects of some methyl-containing compounds added to a choline-deficient diet on the metallothionein mRNA level in the rat liver were studied. The addition of choline or carnitine to the choline-deficient diet did not induce a gain in body weight, while the addition of either betaine or methionine to the choline-deficient diet, or of methionine to the choline-deficient diet with choline significantly increased the body weight. The metallothionein mRNA level in the liver of rats fed on the choline-deficient diet was similar to that of rats fed on the choline-deficient diet with choline, betaine or carnitine. However, the addition of methionine to the choline-deficient diet with or without choline caused a marked suppression in the metallothionein mRNA level in the liver. It is thus surmised that the metallothionein mRNA level in the liver might be regulated by the dietary content of methionine.     

Decreased mRNA expression of the PTH/PTHrP receptor and type II sodium-dependent phosphate transporter in the kidney of rats fed a high phosphorus diet accompanied with a decrease in serum calcium concentration

This study investigates the phosphorus (P) homeostasis in the process of an altered parathyroid hormone (PTH) action in the kidney of rats fed a high P diet. Four-week-old male Wistar strain rats were fed diets containing five different P levels (0.3, 0.6, 0.9, 1.2 and 1.5%) for 21 days. The serum PTH concentration and urinary excretion of P were elevated with increasing dietary P level. Compared to rats fed the 0.3% P diet, the serum calcium (Ca) concentration remained unchanged, while the serum 1,25(OH)(2)D(3) concentration and urinary excretion of cAMP were elevated with increasing dietary P level in rats fed the high P diets containing 0.6-0.9% P. On the other hand, a lower serum Ca concentration was observed in rats fed the high P diets containing 1.2% or greater P. The serum 1,25(OH)(2)D(3) concentration remained unchanged in rats fed the high P diets containing 1.2% or greater P, comparison with rats fed the 0.3% P diet. The urinary excretion of cAMP and PTH/PTH-related peptide (PTHrP) receptor and type II sodium-dependent phosphate transporter (NaPi-2) mRNA in the kidney were both decreased in rats fed the high P diets containing 1.2% or greater P. In conclusion, a high P diet with subsequent decrease in serum Ca concentration suppressed the PTH action in the kidney due to PTH/PTHrP receptor mRNA down-regulation. Furthermore, an increase in the urinary excretion of P might have been caused by decreased NaPi-2 mRNA expression without the effects of PTH and 1,25(OH)(2)D(3).     

Effects in rats of iron on lead deprivation

In two fully crossed, two-factor experiments, F1 generation male rats were fed a basal diet supplemented with lead (lead acetate) at 0 or 2 micrograms/g and iron (ferric sulfate) at 50 or 250 micrograms/g (Experiment 1). Supplements in Experiment 2 were lead at 0 or 1 micrograms/g and iron at 50, 250, or 1000 micrograms/g. After 28 or 50 d in Experiment 1, and 35 d in Experiment 2, a relationship between lead and iron was found. Body weight was lower in low-lead than lead-supplemented 28-d-old rats regardless of dietary iron, whereas hematocrit and hemoglobin were lower in low-lead than lead-supplemented rats fed 50 micrograms iron/g diet. A similar finding was obtained with hematocrit and hemoglobin in 35-d-old rats. Dietary lead did not affect rats fed 250 or 1000 micrograms iron/g diet. Also, feeding low dietary lead did not affect 50-d-old rats regardless of dietary iron. Liver and bone concentrations of lead were markedly affected by dietary lead and iron. The concentration of lead in liver and bone was lower in low-lead than lead-supplemented rats. Compared to rats fed 50 micrograms iron/g diet, rats fed 250 micrograms iron/g diet exhibited a decreased lead concentration in liver and bone. This decrease was accentuated by lead supplementation. The findings suggest that lead acted pharmacologically to affect iron metabolism in rats.     

Effects of Dietary Pyrazinamide on the Metabolism of Tryptophan to Niacin in Streptozotocin-diabetic Rats

We investigated the effects of feeding with a diet containing pyrazinamide (PYR) on the metabolism of l-tryptophan (Trp) to nicotinamide in streptozotocin (STZ)-diabetic rats and whether the diabetic action of STZ is prevented by feeding with the PYR diet, which is known as an inhibitor of aminocarboxy-muconate-semialdehyde decarboxylase and poly(ADP)ribose synthetase and therefore, significantly increases the formation of nicotinamide from Trp in normal rats. As was expected, feeding with the PYR diet to the STZ-injected rats caused a significantly increased excretion of nicotinamide and its metabolites like that in normal rats. The body weight increased in the STZ-injected rats fed with the PYR diet, while it was lost in the STZ-injected rats fed with the non-PYR diet. However, the blood glucose level and the urinary excretion of glucose were not improved even when the rats were fed with the PYR diet. Therefore, it was suggested that chronically increasing the formation of nicotinamide from Trp could not completely prevent the STZ-diabetic action.     

Effect of citrate feeding on free radical induced changes in experimental urolithiasis.

Feeding calculi producing diet (CPD) to rats for 4 weeks produced calcium oxaltate stones. Supplementation of sodium citrate to CPD (c-CPD) prevented stone formation. Except oxalate, the excretion of calcium, phosphorus and magnesium was restored to normal in c-CPD fed rats. The CPD fed rats exhibited increase in glycolic acid oxidase (GAO) and lactate dehydrogenase (LDH) activities and only GAO activity was partially restored in c-CPD fed rats. Kidney sub-cellular fractions of calculi producing diet (CPD) fed rats showed increased susceptibility for lipid peroxidation in presence of promotors. Antioxidant enzyme activities of superoxide dismutase (SOD), catalase and glutathione peroxidase and antioxidant concentrations of reduced glutathione, total thiols, ascorbic acid and vitamin E were significantly decreased while the xanthine oxidase activity, and concentrations of hydroxyl radical, diene conjugates and hydroperoxides were significantly increased in CPD fed rats. The susceptibility to lipid peroxidation, activities of antioxidant enzymes, and the concentration of antioxidants were not normalized by feeding citrate.     

Diet-induced nephrocalcinosis and urinary excretion of albumin in female rats

This study was carried out to test the hypothesis that diet-induced nephrocalcinosis causes enhanced loss of albumin in urine, irrespective of the composition of the nephrocalcinogenic diet. Female rats were fed various purified diets for 28 days. There was a control diet (0.5% Ca, 0.04% Mg, 0.4% P, 15.1% protein, wt/wt), a low Mg (0.01% Mg), a high protein (30.2% protein) and a high P diet (0.6% P). The low Mg and high P diet induced nephrocalcinosis as demonstrated histologically and by markedly increased concentrations of kidney Ca. In rats fed the high protein diet, nephrocalcinosis was essentially absent. Group mean values of urinary excretion of albumin and plasma concentrations of urea were increased in rats fed either the low Mg or high P diet. The high protein diet did not affect urinary albumin but caused lysozymuria which was not seen in the other groups. Plasma urea was increased in rats fed the high protein diet. In individual rats, the concentration of Ca in kidney and urinary albumin excretion were positively correlated. It is suggested that nephrocalcinosis in female rats induced by either low Mg or high P intake causes kidney damage which in turn leads to increased concentrations of albumin in urine and urea in plasma.