Effect of Chlorella vulgaris intake on cadmium detoxification in rats fed cadmium

The aim of this study was to investigate if dietary Chlorella vulgaris (chlorella) intake would be effective on cadmium (Cd) detoxification in rats fed dietary Cd. Fourteen-week old male Sprague-Dawley (SD) rats weighing 415.0 ± 1.6 g were randomly divided into two groups and fed slightly modified American Institute of Nutrition-93 Growing (AIN-93G) diet without (n=10) or with (n=40) dietary Cd (200 ppm) for 8 weeks. To confirm alteration by dietary Cd intake, twenty rats fed AIN-93G diet without (n=10) and with (n=10) dietary Cd were sacrificed and compared. Other thirty rats were randomly blocked into three groups and fed slightly modified AIN-93G diets replacing 0 (n=10), 5 (n=10) or 10% (n=10) chlorella of total kg diet for 4 weeks. Daily food intake, body weight change, body weight gain/calorie intake, organ weight (liver, spleen, and kidney), perirenal fat pad and epididymal fat pad weights were measured. To examine Cd detoxification, urinary Cd excretion and metallothonein (MT) concentrations in kidney and intestine were measured. Food intake, calorie intake, body weight change, body weight gain/calorie intake, organ weight and fat pad weights were decreased by dietary Cd intake. Urinary Cd excretion and MT concentrations in kidney and small intestine were increased by dietary Cd. After given Cd containing diet, food intake, calorie intake, body weight change, body weight gain/calorie intake, organ weights and fat pad weights were not influenced by dietary chlorella intake. Renal MT synthesis tended to be higher in a dose-dependent manner, but not significantly. And chlorella intake did not significantly facilitate renal and intestinal MT synthesis and urinary Cd excretion. These findings suggest that, after stopping cadmium supply, chlorella supplementation, regardless of its percentage, might not improve cadmium detoxification from the body in growing rats.     

Iron body status of rats chronically exposed to cadmium and ethanol

AIMS: The present study was performed to assess the effect of simultaneous long-term exposure to cadmium (Cd) and ethanol on iron (Fe) status of male Wistar rats. METHODS: The animals received drinking water containing 50 mg of Cd/l and/or 10% (w/v) ethanol for 12 weeks. Fe and Cd concentrations in serum (blood), certain tissues, urine and feces were determined by atomic absorption spectrometry. The total pool of Fe was calculated as a sum of its content in liver, spleen, kidneys, heart and brain. Fe bioavailability was evaluated based on its apparent absorption. RESULTS: The daily Cd intake ranged from 3.17 to 4.28 mg/kg (Cd group) and from 2.41 to 3.17 mg/kg (Cd + ethanol group); ethanol consumption ranged from 47.5 to 86.9 g/kg/24 h (ethanol group) and from 47.3 to 63.4 g/kg/24 h (Cd + ethanol group). Exposure to Cd or/and ethanol caused serious disturbances in Fe metabolism, as indicated by Fe body depletion. Both substances, applied alone and in combination, reduced the apparent Fe absorption and decreased its total pool in certain organs, and urinary excretion. However, the Cd- and ethanol-induced changes in the tissue Fe concentrations were different. Cd exposure decreased the concentration of Fe in serum, liver, spleen and femur, whereas ethanol decreased it in the spleen. In rats co-exposed to Cd and ethanol, decreased serum, spleen and brain Fe concentrations were all observed. CONCLUSIONS: The changes in Fe status in rats co-exposed to Cd and ethanol can be explained by the independent action of the two substances, leading to a decrease in Fe bioavailability, or by their interactions, which involves a modifying effect of ethanol on Cd turnover. The results allow the conclusion that ethanol may increase Cd accumulation, making the organism more susceptible to Fe depletion. Alcoholics thus may be at increased risk of disorders in Fe body status.     

Cadmium turnover and changes of zinc and copper body status of rats continuously exposed to cadmium and ethanol

The effects of continuous exposure to cadmium (Cd) and ethanol on Cd turnover and zinc (Zn) and copper (Cu) body status of male Wistar rats were studied. The animals received an aqueous solution of 10% (w/v) ethanol and/or 50 mg Cd/l as the only drinking fluid for 12 weeks. The concentrations of Zn, Cu and Cd in the serum (or blood), liver, kidneys, spleen, brain, heart, femoral muscle and femur as well as in 24-h urine and faeces specimens were assessed by atomic absorption spectrometry (AAS). Ethanol alone had no effect on Cd accumulation or excretion. By contrast, co-administration of ethanol with Cd influenced the turnover of this toxic metal. Long-term consumption of ethanol alone caused a decrease in femur Zn and liver Cu concentrations. Moreover, the urinary loss of both bioelements decreased, whereas their faecal excretion was increased. Exposure to Cd resulted in an increase in liver and kidney and in a decrease in femur and 24-h urine Zn concentrations. An increase in Cu concentration in the kidney and a decrease in the brain were also noted. Moreover, Cd increased the total pool of Zn in organs (kidneys, liver, spleen, heart and brain), but did not influence that of Cu. Zn concentration in the liver, kidney and spleen of rats co-exposed to Cd and ethanol were increased, but were decreased in the brain and femur, compared to controls. The concentrations of Cu in livers and brains of these rats were decreased, whereas those in kidney, spleen and heart were increased. The urinary excretion of the elements was decreased, whereas their faecal excretion was increased. Moreover, the total amount of Cu in organs decreased below the control value and that of Zn was in the normal range. These changes in Zn and Cu levels could be explained by different effects of both toxic substances, differences in bioelement intakes (due to reduced consumption of drinking solutions and food), and the modifying effect of ethanol on Cd turnover. Our results suggest that alcoholics may be more susceptible to Cd accumulation and its effects on body Zn and Cu.     

Effect of zinc deficiency on the accumulation of metallothionein and cadmium in the rat liver and kidney

The effects of zinc (Zn) deficiency and repeated exposure to cadmium (Cd) on the accumulation and distribution of metallothionein (MT), Cd and Zn in the liver and kidney were studied. Male Sprague-Dawley rats were fed either a Zn-deficient (1 ppm) or a Zn-adequate (40 ppm) diet during the experiment, and the rats were injected subcutaneously with a cadmium chloride solution (1.0 mg Cd/kg of body weight, 5 days a week) for 4 weeks. Cadmium, Zn, and Cd-induced MT concentrations in the liver and kidney were lower in the Zn-deficient rats (–Zn + Cd) than in the Zn-adequate rats (+ Zn + Cd), while the content of Cd bound to high molecular weight proteins (HMWP) was greater in the Zn-deficient rats (–Zn + Cd). The Zn bound to Cd-induced MT was reduced to 30% in the liver and to 60% in the kidney of the Zn-deficient rats (–Zn + Cd) as compared with that of the Zn-adequate rats (+ Zn + Cd). In the kidney of Zn-deficient rats, exposure to Cd caused a decrease in essential Zn associated with HMWP as compared with that of Zn-adequate rats (+ Zn + Cd). Thus, Zn-deficiency affected the distribution of Cd in tissues, MT and HMWP and accelerated substantially Cd-induced Zn-deficiency in the kidney. Although the renal Cd concentration was lower in the Zn-deficient rats (–Zn + Cd) than in the Zn-adequate rats (+ Zn + Cd), exposure to Cd for four weeks resulted in glucosuria and an increase in liver and kidney weights in the Zn-deficient rats (–Zn + Cd), but not in the Zn-adequate rats (+ Zn + Cd). These results suggest that development of Cd toxicity is related to the Zn status of the body, to the accumulation of Cd in HMWP and to the amount of essential Zn associated with HMWP.     

Cadmium in blood and urine--impact of sex,age, dietary intake,iron status,and former smoking--association of renal effects

We studied determinants of cadmium status and kidney function in nonsmoking men and women living on farms in southern Sweden. Median blood Cd (BCd) was 1.8 nmol/L (range, 0.38-18) and median urinary Cd (UCd) was 0.23 nmol/mmol creatinine (range, 0.065-0.99). The intake of Cd per kilogram body weight did not significantly differ between sexes and did not correlate with BCd or UCd, which may be explained by a low and varying bioavailibility of Cd from food items. However, when a subgroup of the study population, couples of never-smoking men and women, were compared, a lower intake per kilogram body weight was found in the women, but the women had a 1.8 times higher BCd and a 1.4 times higher UCd. The higher female BCd and UCd may be explained by higher absorption due to low iron status. BCd and UCd both increased with age and were higher in the ex-smokers, who had stopped smoking more than 5 years before the study, compared to never-smokers. The contribution of locally produced food to the total Cd intake was relatively low and varied. Males living in areas with low soil Cd had lower UCd than the others. However, Cd levels in kidneys from pigs, fed locally produced cereals, did not predict BCd or UCd in humans at the same farms. The kidney function parameter ss2-microglobulin-creatinine clearance was related to UCd, whereas urinary protein-HC, N-acetyl-ss-glucoseaminidase or albumin-creatinine clearance was not when age was accounted for. Hence, even at the low exposure levels in this study population, there was an indication of effect on biochemical markers of renal function.     

Safe levels of cadmium intake to prevent renal toxicity in human subjects

The present review attempts to provide an update of the scientific knowledge on the renal toxicity which occurs in human subjects as a result of chronic ingestion of low-level dietary Cd. It highlights important features of Cd toxicology and sources of uncertainty in the assessment of health risk due to dietary Cd. It also discusses potential mechanisms for increased susceptibility to Cd toxicity in individuals with diabetes. Exposure assessment on the basis of Cd levels in foodstuffs reveals that vegetables and cereals are the main sources of dietary Cd, although Cd is also found in meat, albeit to a lesser extent. Cd accumulates particularly in the kidney and liver, and hence offal contains relatively high amounts. Fish contains only small quantities of Cd, while crustaceans and molluscs may accumulate larger amounts from the aquatic environment. Data on Cd accumulation in human kidney and liver obtained from autopsy studies are presented, along with results of epidemiological studies showing the relationship between renal tubular dysfunction and kidney Cd burden. These findings suggest that a kidney Cd level of 50 microg/g wet weight is a maximum tolerable level in order to avoid abnormal kidney function. This renal Cd burden corresponds to a urinary Cd excretion of 2 microg/d. Accordingly, safe daily levels of Cd intake should be kept below 30 microg per person. Individual variations in Cd absorption and sensitivity to toxicity predicts that a dietary Cd intake of 30 microg/d may result in a slight renal dysfunction in about 1% of the adult population. The previous guideline for a maximum recommended Cd intake of 1 microg/kg body weight per d is thus shown to be too high to ensure that renal dysfunction does not occur as a result of dietary Cd intake.     

Phosphorus-induced nephrocalcinosis and kidney function in female rats

The question was addressed whether dietary phosphorus-induced nephrocalcinosis in rats is associated with impaired kidney function. Weanling female rats were fed purified diets containing either 0.4 or 0.6% (wt/wt) phosphorus for 28 d. The diet containing 0.6% phosphorus produced marked kidney calcification, as determined both by chemical analysis of kidney calcium and histological examination in kidney sections. Histological examination did not show calcification in stomach, lung, heart or thoracic aorta, which are predisposition sites of metastatic calcification in secondary renal hyperparathyroidism. In rats fed the 0.6% phosphorus diet, phosphorus retention and urinary excretion were greater compared with rats fed the 0.4% phosphorus diet. The following indicators of kidney function were examined: water intake, urinary volume, urine and plasma osmolality, urine and plasma creatinine, urine and plasma urea, urea and creatinine clearance and urinary albumin excretion. Of these indicators, only urinary albumin excretion was significantly increased in rats fed the nephrocalcinogenic diet. In a further experiment, the increase of urinary albumin was reproduced. After pooling the results of the two experiments, in individual rats fed the 0.6% phosphorus diet, the concentration of kidney calcium was found to be positively related with kidney weight expressed relative to body weight (r = 0.82, n = 22) and with albumin excretion in urine (r = 0.79, n = 28). The increased weight of calcinotic kidneys was mainly due to both calcium deposition and tubular hyperplasia. It is concluded that dietary phosphorus-induced nephrocalcinosis is associated with impaired kidney function in rats.     

Effect of L-ascorbic acid supplementation on the toxicity of pirimiphos-methyl to albino rats

The effect of L-ascorbic acid supplementation on Pirimiphos-methyl induced toxicity was studied in albino rats. Biochemical estimations were made in rats administered orally the insecticide at 100 and 200 mg/kg body weight with or without oral supplementation of L-ascorbic acid at 200 mg/kg b.w. The biochemical assessments included estimations of brain and plasma cholinesterases, levels of ascorbic acid in liver, kidney and adrenals, urinary levels of ascorbic acid and glucuronic acid. A lower degree of inhibition of the cholinesterases were evident in ascorbic acid supplemented rats. Marked elevation in urinary levels of ascorbic acid and glucuronic acid was observed in the insecticide treated rats. Results of this study suggests that L-ascorbic acid supplementation partially offsets Pirimiphos-methyl induced toxicity.     

Effects of low-level cadmium in rats: influence of pretreatment with thiol-modulating agents

The effects of low-level cadmium (Cd) administration to rats on animal health, liver and kidney thiols, metallothionein, and glutathione reductase (GSSG reductase) and their modulation by cysteine (as a possible protector) and diethyl maleate (as a possible potentiator) have been investigated. Male Sprague-Dawley rats were treated with sodium or Cd acetate (25 micrograms Cd/kg) orally five times a week for 6 weeks. A second group of animals received cysteine (500 mg/kg; po) before each gavage while a third group received diethyl maleate (DEM) (0.85 mg/kg; ip) in addition to sodium or Cd acetate. When rats were treated with cadmium alone neither weight gain nor serum parameters indicative of hepato- or nephro-toxicity were affected. However, acid-soluble thiols, primarily glutathione, were decreased by about 25% in liver only. A tendency to a decrease in hepatic protein thiols was also noted. No changes were observed for hepatic or renal metallothionein in response to this low level of cadmium administration alone or in combination with the other treatments. Animals receiving cysteine, either alone or with cadmium, showed decreased body weight gain, but no change in serum parameters. Acid-soluble thiols in liver were lower in cysteine-treated rats (24%) and cysteine + Cd (33%) while kidney thiols were unaffected. Administration of DEM alone or with Cd did not cause any alteration in body weight gain. When given DEM + Cd, however, an increase in serum bilirubin was observed, which suggests interference with hepatobiliary function. Acid-soluble thiols were decreased by DEM alone (45%) and DEM + Cd (51%) in liver while renal thiols showed no change. Our data indicate that low-level Cd gavage decreases hepatic cellular thiols but not those of kidney. Cysteine gavage does not protect from the Cd-related effect. Indeed, cysteine itself was found to reduce acid-soluble thiols under the experimental conditions. This was observed only in liver, as was the decrease in thiols due to DEM treatment. DEM administration together with Cd resulted in signs of liver toxicity. There is no indication that inhibition of GSSG reductase by Cd might be involved in the thiol-decreasing effect of short-term repeated low-level gavage of Cd to rats.     

镉对孕期、哺乳期大鼠及仔代铁代谢的影响

采用含有正常足量铁（２３０ｍｇ／ｋｇ）和不同剂量镉（０，２５ｍｇ／ｋｇ，８５ｍｇ／ｋｇ）的饲料喂饲妊娠和哺乳大鼠以探讨镉对微量元素铁代谢的可能影响。结果显示，低剂量与高剂量的镉均可导致孕鼠和哺乳大鼠体内多器官和组织中镉的蓄积和铁含量下降，肝、肾受累最甚。胎盘和乳腺似有某种屏障作用阻止镉由母体经胎盘和乳汁侵染子代，各实验组动物乳汁及胎鼠、幼鼠脏器中镉含量极低并无组间差异。但镉对铁代谢的干扰作用引起母体组织中的铁含量下降，对子代动物的铁营养产生极明显的影响，与对照组比较，低镉组和高镉组胎鼠全尸铁含量分别下降了２２．５％和５７．１％，幼鼠肝脏铁含量下降了５８％和６７％，脾脏铁减少了１５％和３７％。     

Availability and toxicological effects of low levels of biologically bound cadmium

Rats were fed a casein based diet containing Cd biologically bound in ryegrass (Lolium multiflorum L. ssp. italicum) for eight weeks. The grass portion in the diet was 20% (w/w). Cd concentrations of the respective diets were (g/g diet): 0.24 (control group Cd=0), 0.85 (group Cd=1) and 2.25 (group Cd=2). After six weeks on the diets, food intake and body weight were reduced by the low dietary Cd concentration (Cd=1), while in treatment group Cd=2 this occurred after 2 weeks. After an 8-week feeding period the concentrations of Cd, Cu, Zn, Fe and Ca in selected organs, tissues and in the excreta of rats beside whole body element contents were determined. While no elevated Cd levels due to the Cd intoxication were found in skin, lung, blood, testes, muscle and urine, Cd concentrations in liver, kidney and spleen increased in a dose-dependent manner. This was also true for whole body Cd and Cd in faeces, the latter being 27.6 fold higher in the high Cd load (Cd=2) as compared to the controls (Cd=0). Highest Cd concentrations were recorded in liver and kidney. Calculated as percentage of the whole body metal content liver Cd increased from 1.49% (Cd=0) to 7.41% (Cd=2) and kidney Cd from 0.65% to 4.87%. While no changes of the Ca levels in all organs and tissues investigated were observed, liver Zn increased and blood Cu decreased. Copper and Zn increased in faeces and decreased in urine. With the exception of skin and lung, a significant loss of Fe was observed in all organs and tissues, which was most evident in treatment group Cd=2. Depending on the Cd dose applied, reduced fecal and urinary Fe excretion occurred. Hematological parameters (hemoglobin, hematocrit, blood glucose) and serum enzyme activities (alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, -glutamyl transferase) were not affected by Cd in a biologically bound form. Serum alanine amino transferase showed slightly lower activities in treatment groups Cd=1 and Cd=2. Analysis of the glucose concentration and the activity of alkaline phosphatase in urine did not reveal any changes due to the Cd intoxication. Accumulation and toxicological effects of Cd biologically bound in ryegrass are discussed in relation to inorganic forms of the metal administered to mammals.     

Relationship between renal dysfunction and bone metabolism disorder in male rats after long-term oral quantitative cadmium administration

To investigate the importance of the cadmium (Cd) exposure condition in the evaluation of toxic effect on renal function and bone metabolism, six groups of Male Wistar rats were given Cd at respective daily doses of 2, 5, 10, 20, 30 and 60 mgCd/kg (as CdCl2) via a gastric tube for 6 consecutive days a week for 60 weeks. In the groups given a low Cd dose (2, 5 and 10 mgCd/kg), relatively more Cd accumulated in the kidney without liver damage than in the liver. In the high Cd dose groups (20, 30 and 60 mgCd/kg), on the other hand, more Cd accumulated in the liver than in the kidney. The daily intake of Cd dose from the intestinal tract in each experimental group was deduced to be about 0.36%-0.54% of the cumulative dose of oral Cd administration. The daily intake of Cd into the body was estimated as 7, 22, 40, 100, 120, 260 microgCd/kg/day in the experimental groups of 2, 5, 10, 20, 30 and 60 mgCd/kg/day, respectively. Increase of plasma enzyme activity (GOT, GPT) and of urinary enzyme excretion (NAG, AAP, GST), reflecting hepatic damage and renal dysfunction, was found in the high Cd dose groups (30 and 60 mgCd/kg) from the 5th week. Non-CdMT concentration in the kidney was also significantly high in the high Cd dose groups. In the low Cd dose groups (2 and 5 mgCd/kg), although the renal Cd concentration was higher than that of the high Cd dose groups, prominent renal dysfunction and hepatic damage were not observed. Regeneration, vacuolization, and eosinophilic bodies in proximal tubular tissue were mainly observed in the groups subjected to 20, 30 and 60 mgCd/kg administration. Very slight regeneration was also observed in the renal proximal tubular tissue at the 30th week for the 5 mgCd/kg and 10 mgCd/kg groups, and at the 60th week for the 2 mgCd/kg group. Remarkable decrease of bone mineral density at the midpoint of the femur was found in the high Cd dose groups. Also, the decrease in bone mineral density was observed before or after the manifestation of the renal dysfunction, depending on the dose and the duration of Cd administration. Urinary excretion of Pyr, DPyr, and Ca increased and plasma BGP decreased in the higher Cd dose groups. Osteoid volume in the femur tissue was not increased significantly by Cd exposure. Based on these results, it was suggested that Cd exposure caused osteoporotic change. The results of the present study suggested that the toxic effect of Cd on renal function and that on bone metabolism were caused at different times and that renal Cd concentration after long-term oral Cd administration depended on the dose and the duration of Cd exposure.     

Supplementation of fenugreek leaves lower lipid profile in streptozotocin-induced diabetic rats

The present study was undertaken to evaluate the lipid-lowering effect of fenugreek leaves in diabetes mellitus. Albino Wistar rats were randomly divided into six groups: normal untreated rats; streptozotocin (STZ)-induced diabetic rats; STZ-induced rats + fenugreek leaves (0.5 g/kg of body weight); STZ-induced rats + fenugreek leaves (1 g/kg of body weight); STZ-induced rats + glibenclamide (600 microg/kg of body weight); and STZ-induced rats + insulin (6 units/kg of body weight). Rats were made diabetic by STZ (40 mg/kg) injected intraperitoneally. Fenugreek leaves were supplemented in the diet daily to diabetic rats for 45 days, and food intake was recorded daily. Blood glucose, total cholesterol, triglycerides, and free fatty acids were determined in serum, liver, heart, and kidney. Our results show that blood glucose and serum and tissue lipids were elevated in STZ-induced diabetic rats. Supplementation of fenugreek leaves lowered the lipid profile in STZ-induced diabetic rats.     

Regulatory responses to excess zinc ingestion in growing rats

The growth of weaning piglets is effectively improved by feeding a high-Zn diet (3000 mg Zn/kg of diet). The present study examined whether feeding a diet supplemented with Zn (1016-3000 mg/kg) for 10 d induces growth benefits in rats. In addition, tissue weight, Zn content of tissues and expression of Zn transporters were examined in these rats. Zn supplementation did not significantly increase body weight. Breaking line model analyses indicated that the weight of the pancreas, the organ most sensitive to excess Zn, significantly decreased with increasing Zn intake beyond 15·2 mg/d. Excess Zn has been suggested to accumulate in the liver, kidney and bone in order to protect the pancreas. Zn concentrations in the plasma, liver, kidney and femur increased with increasing Zn intake up to approximately 30 mg/d, whereas those in the pancreas increased up to 8·4 mg/d and decreased by Zn intake beyond 8·4 mg/d. The expression levels of the Zn transporters Zip4 and ZnT1 in the intestinal epithelium were significantly lower in rats fed a diet supplemented with 1016 mg/kg Zn compared to those fed the basal diet. The present study reveals that (1) excess Zn intake does not accelerate growth in rats, but is detrimental to the pancreas, (2) the excess Zn is effectively accumulated in the liver, kidney and bone, without sufficient protection of the pancreas and (3) expression of Zn transporters is down-regulated in response to excess Zn intake.     

镉中毒对血清AKP活性影响的实验研究

用Ｗｉｓｔａｒ大鼠镉染毒后测定其血清ＡＫＰ值、尿镉、尿肌酐、肝脏重量系数与肾脏重量系数等指标，结果与对照组相比，均有显著性差异（Ｐ＜０．０１）。提示实验组大鼠镉染毒后，肾脏与肝脏损伤，导致血清ＡＫＰ值的下降。     

Toxicity of sodium fluoride to the postnatally developing rat kidney

The adult rat kidney is an important target organ for sodium fluoride; however, the toxicity of fluoride to the developing kidney is unknown. This study examined renal function following NaF exposure during the first 4 weeks after birth. Sprague-Dawley rats received a single ip injection of 0, 30, or 48 mg/kg NaF on postnatal Day 1, 8, 15, or 29. Alterations in renal function, histology, and morphology were determined 24, 48, and 120 hr after exposure. Measurements of renal function included urine volume, osmolality, the ability to concentrate urine during water deprivation, urinary pH, and chloride content. Rats were then sacrificed and their kidneys processed for observation by light microscopy. Some minor alterations in renal function were observed in the three youngest age groups after NaF exposure. These changes included decreased body weight after treatment with 30 or 48 mg/kg NaF but increased kidney-body weight ratio in the 48 mg/kg group on Day 1; decreased urinary pH in both dose groups after treatment on Day 1 or 8; increased urinary volume 120 hr after treatment on Day 8; and decreased chloride excretion in the 48 mg/kg group 24 hr after injection on Day 1. None of these effects was severe. In contrast to these results, marked renal toxicity was observed in postweaning rats treated on Day 29. The NaF exposure resulted in increased kidney weight and kidney/body weight ratio, profound diuresis, decreased urinary osmolality, and decreased ability to concentrate urine during water deprivation. Urinary chloride excretion was decreased for the first 2 days after NaF exposure, then increased in water-deprived rats 120 hr after treatment. Glucosuria and hematuria were present for 2 days after treatment with 48 mg/kg. Histological lesions were apparent in the proximal tubules of the treated Day 29 rats. Thus, the kidney of the suckling rat is largely unresponsive to NaF toxicity. Renal sensitivity increases abruptly after weaning in the Day 29 rat.     

Daily salt intake of healthy Japanese infants of 3-5 years based on sodium excretion in 24-hour urine

We measured concentrations of sodium and creatinine in previously validated overnight urine and 24-h urine of 79 healthy infants of 3 to 5 y of age in two cities in Miyagi Prefecture, Japan. Thereafter, we estimated daily salt intake from daily urinary sodium excretion and daily urinary volume. Corrections for potential sweat loss of sodium chloride were conducted based on urinary volume and urinary creatinine concentration. We also measured urinary volume and urinary sodium concentration in infants who failed to provide complete urine samples. The estimated salt intake did not differ between boys and girls, but varied between the two cities. The estimated salt intake per unit of body weight differed neither between genders nor between cities. The grand means for estimated salt intake and that per unit of body weight were 5.5 g/d (SD 1.8) and 0.32 g/kg/d (SD 0.10), which supported previous results both in Japan and abroad. It was also possible to roughly estimate salt intake from sodium concentration in overnight urine or incomplete 24-h urine, and published urine volume.     

Toxicity,fertility, teratogenicity,and dominant lethal tests in rats administered cadmium subchronically: I. Toxicity studies

In order to obtain an overall understanding of the toxicity of cadmium (Cd), a single experimental series was designed to investigate the diverse effects of Cd. Four groups of Sprague-Dawley rats, each of which consisted of 14 male and 14 female rats, were administered Cd (CdCl₂) orally at dose levels of 0, 0.1, 1.0, 10.0 mg/kg/day for 6 weeks. After this, the animals were mated for 3 weeks, changing partners every week, for fertility and teratogenicity tests. Cd was given during this mating period. Females were administered Cd during gestation and sacrificed on the 20th day of gestation for fetal examination. After a total of 9 weeks administration, males were subjected to dominant lethal tests by mating 2 females per male per week for 6 weeks. Pregnant females were killed on the 13th day of gestation to test for dominant lethality. This paper reports the results of the general toxicity tests. The main toxic signs, seen only in the 10 mg/kg group, were repression of food intake and body weight gain, depilation, whitening of the incisors, and salivation. Hematological analyses showed that the number of RBC increased while hemoglobin and hematocrit levels decreased, and the number of WBC increased, mainly as a result of neutrophilia. Serum biochemical analyses indicated increased levels of GPT and creatinine, reflecting damage to the liver and kidneys. Increased glucose levels were seen in males. A major change found at the time of autopsy by macroscopic observation of organs was hypertrophy of the jejunum and ileum with a darkish-brown color in nonpregnant females of the 10 mg/kg group. Microscopically, hyperplasia with a high frequency of mitotic figures was seen in the lamina propria mucosae. The weight of the thymus decreased and the weight of the adrenals increased in both males and females. The weight of the ovaries decreased. Major histopathological changes were focal necrosis in the liver and hyperplasia of the adrenal cortices with patchy necrosis in nonpregnant females of the 10.0 mg/kg group. Determination of Cd in the liver and kidneys suggested that excretion of the accumulated Cd was slow. Two aspects of Cd toxicity, i.e., the inhibition of nutrient resorption by unresorbed Cd and the toxicity expressed by resorbed Cd, as well as the causative factors of the adrenal hyperplasia, are discussed.     

Zinc deficiency negatively affects alkaline phosphatase and the concentration of Ca, Mg and P in rats

Zn is an essential nutrient that is required in humans and animals for many physiological functions, including immune and antioxidant function, growth, and reproduction. The present study evaluated whether Zn deficiency would negatively affect bone-related enzyme, ALP, and other bone-related minerals (Ca, P and Mg) in rats. Thirty Sprague Dawley rats were assigned to one of the three different Zn dietary groups, such as Zn adequate (ZA, 35 mg/kg), pair fed (PF, 35 mg/kg), Zn deficient (ZD, 1 mg/kg) diet, and fed for 10 weeks. Food intake and body weight were measured daily and weekly, respectively. ALP was measured by spectrophotometry and mineral contents were measured by inductively coupled plasma-mass spectrophotometer (ICP-MS). Zn deficient rats showed decreased food intake and body weight compared with Zn adequate rats (p<0.05). Zn deficiency reduced ALP activity in blood (RBC, plasma) and the tissues (liver, kidney and small intestine) (p<0.05). Also, Zn deficiency reduced mineral concentrations in rat tissues (Ca for muscle and liver, and Mg for muscle and liver) (p<0.05). The study results imply the requirement of proper Zn nurture for maintaining bone growth and formation.     

Effect of astaxanthin in combination with alpha-tocopherol or ascorbic acid against oxidative damage in diabetic ODS rats

The present study was performed to investigate the effect of astaxanthin in combination with other antioxidants against oxidative damage in streptozotocin (STZ)-induced diabetic Osteogenic Disorder Shionogi (ODS) rats. Diabetic-ODS rats were divided into five groups: control, astaxanthin, ascorbic acid, alpha-tocopherol, and tocotrienol. Each of the four experimental groups was administered a diet containing astaxanthin (0.1 g/kg), in combination with ascorbic acid (3.0 g/kg), alpha-tocopherol (0.1 g/kg), or tocotrienol (0.1 g/kg) for 20 wk. The effects of astaxanthin with other antioxidants on lipid peroxidation, urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) excretion, serum creatinine (Cr) level, creatinine clearance (Ccr), and urinary protein content were assessed. The serum lipid peroxide levels and chemiluminescent (CL) intensity in the liver of the alpha-tocopherol and tocotrienol groups were significantly reduced in comparison to that of the control group. In the alpha-tocopherol group, urinary 8-OHdG excretion, serum Cr level, Ccr, urinary albumin excretion, and urinary protein concentration were significantly decreased as compared with those in the control group. Additionally, the CL intensity in the kidney of the alpha-tocopherol group was significantly lower, but that of the ascorbic acid group was significantly higher than that in the control group. These results indicate that dietary astaxanthin in combination with alpha-tocopherol has an inhibitory effect on oxidative stress. On the other hand, our study suggests that excessive ascorbic acid intake increases lipid peroxidation in diabetic rats.