• Journal of Nutrition and Health
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• v.33 no.7
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• pp.725-732
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• 2000

The purpose of this study was to investigate the effects of green tea catechin on renal dysfunction and blood presure change in chronic cadmium poisoned rats. Sprague-Dawley male rats weighing 100$\pm$10g were randomly assigned to one normal group and three cadmium poisoned groups. Cadmium groups were classified to catechin free diet(Cd-0C group) 0.25% catechin diet(Cd-0.25C group) and 0.5% catechin diet(Cd-0.5C group) according to the levels of catechin supplement. Animals were raids for 20weeks. Cadmium were supplied as drinking water of 50ppm Cd2+ Morphological changes shown through a light microscope and an electro-microscope revealed the mitochondria and tubule epithelial cell edema in Cd -0C group but they were alleviated in catechin supplementation. The urinary $\beta$2-microglobulin that measured to observe the glomerular injury were higher in Cd-poisoned groups than in normal group but they was lowered by catechin supplementation. Glomerular filtration ratios(GFR) in Cd-poisoned groups were significantly lower than in normal group but that of catechin supplementation group was similar to normal group. This suggested that catechin protected the kidney from the functional damage. Angiotensin converting enzyme(ACE) activity and blood pressure(BP) in Cd-poisoned groups were significantly higher than in normal group. Heart rate was tended to increase in Cd-poisoned groups. The results indicate that green tea catechin supplementation on chronic cadmium-poisoned rats normalized the renal dysfunction and blood pressure system.

• Journal of Nutrition and Health
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• v.29 no.10
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• pp.1059-1071
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• 1996

This study was performed to investigate the effect of dietary protein level on renal senescence. Male rats of 337.8$\pm$5.7g body weight were underlateral nephrectomy or shamoperation. The rats were divided into high protein(40% casein), normal protein(15% casein) and low protein(8% casein)diets and fed experimental diets ad libitum for 24 weeks. The results are summarized as follows. There was a hypertophy of the remnant kidney of uninephrectomized rats of 40% or 15% protein group, coming up to the comparable weights of both kidneys of sham-operated rats. However, the hypertrophic effect was not seen in uninephrectomized rats of 8% protein group. Serum albumin was lower in uninephrectomized rats. With increasing dietary protein level blood urea nitrogen was increased, whereas, urinary urea nitrogen excretion was decreased. Urinary solute excretion was higher in uninephrectomized group than in sham-operated group. However, effect of dietary protein level on urinary solute excretion varied dpending on th solutes tested. GFR and urinary protein excretion, throughout experiment, increased with feeding period and with dietary protein level. Proteinuria was most severe in uninephrectomized rats fed 40% casein diet. Maximum urine concentration ability measured after dehydration was not different among the experimental groups. Light microscopic examination showed focal segmental glomerulosclerosis and mild increas of glomerular mesangial matrix in uninephrectomized rats fed 40% and 15% protein diet, however, which was not observed in uninephrectomized rats fed 8% protein diet and in sham-operated rats fed 40% diet. Immunofluorescence studies revealed segmental deposits of albumin in the mesangium and capillary loops in high protein and uninephrectomized groups. Minimal granular deposition of IgG was noted in the mesangium of all experimental groups. In conclusion, high protein intake accelerated deterioration of renal function and it was correlated with morphological change. Low protein intake was effective in preventing these changes.

• Toxicological Research
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• v.17 no.2
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• pp.123-129
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• 2001

This study were carried out to investigate cytotoxicity of paraquat and bentazon that is scattering to farm products were essensial for human diet and compensatory effects of 3-methylcholanthrene (3-MC) in vitro and in vivo. In vitro, The 5.0$\times$$10^4$ cell/ml of NIH 3T3 fibroblast in each well of 24 multidish were cultured. After 24 hours, the cells were treated with solution of paraquat and bentazon (1, 25, 50, 100 pM respectively). After the NIH 3T3 fibroblast of all groups were cultured in same condition for 48 hours, Sulfohordamin B Protein (SRB) assay were performed to evaluate the cytotoxicity of cell organelles. Paraquat and bentazon $SRB_50$ were 1860.73 $\mu\textrm{M}$, 1913.38 $\mu$M respectively. In vivo, Sprague Dawley male rats divided into paraquat and bentazon only administered group and simultaneous application group of paraquat and bentazon and 3-MC. At 30 min. and 1, 3, 6, 12, 24, 48 and 96 hrs. interval after each treatment, the animals were sacrificed by decapitation and kidney were immediately removed, immersed in fixatives, and processed with routine method for light microscopic study. Paraffin sections were stained with H-E, PAM, and PAS. Under the light microscope, atrophic change of renal corpuscles were frequently observed from 3 hrs after paraquat and bentazon treatment. The increase of the mesangium was apparent from 12 hrs later after paraquat and bentazon treatment. Necrotic changes of the epithelium and loss of brush border of proximal tubules were most severe at 48 hrs after paraquat and bentazon treatment, respectively. In contrast there were no evidences of the toxic effects on renal tissues at 48hrs in paraquat and bentazon plus 3-MC treated groups.

• Toxicological Research
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• v.34 no.2
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• pp.111-125
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• 2018

Solvents can be used in the manufacture of medicinal products provided their residual levels in the final product comply with the acceptable limits based on safety data. At worldwide level, these limits are set by the "Guideline Q3C (R6) on impurities: guideline for residual solvents" issued by the ICH. Diisopropyl ether (DIPE) is a widely used solvent but the possibility of using it in the pharmaceutical manufacture is uncertain because the ICH Q3C guideline includes it in the group of solvents for which "no adequate toxicological data on which to base a Permitted Daily Exposure (PDE) was found". We performed a risk assessment of DIPE based on available toxicological data, after carefully assessing their reliability using the Klimisch score approach. We found sufficiently reliable studies investigating subchronic, developmental, neurological toxicity and carcinogenicity in rats and genotoxicity in vitro. Recent studies also investigated a wide array of toxic effects of gasoline/DIPE mixtures as compared to gasoline alone, thus allowing identifying the effects of DIPE itself. These data allowed a comprehensive toxicological evaluation of DIPE. The main target organs of DIPE toxicity were liver and kidney. DIPE was not teratogen and had no genotoxic effects, either in vitro or in vivo. However, it appeared to increase the number of malignant tumors in rats. Therefore, DIPE could be considered as a non-genotoxic animal carcinogen and a PDE of 0.98 mg/day was calculated based on the lowest No Observed Effect Level (NOEL) value of $356mg/m^3$ (corresponding to 49 mg/kg/day) for maternal toxicity in developmental rat toxicity study. In a worst-case scenario, using an exceedingly high daily dose of 10 g/day, allowed DIPE concentration in pharmaceutical substances would be 98 ppm, which is in the range of concentration limits for ICH Q3C guideline class 2 solvents. This result might be considered for regulatory decisions.

• Toxicological Research
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• v.34 no.2
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• pp.143-150
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• 2018

It has been demonstrated that vanadate causes nephrotoxicity. Vanadate inhibits renal sodium potassium adenosine triphosphatase (Na, K-ATPase) activity and this is more pronounced in injured renal tissues. Cardiac cyclic adenosine monophosphate (cAMP) is enhanced by vanadate, while increased cAMP suppresses Na, K-ATPase action in renal tubular cells. There are no in vivo data collectively demonstrating the effect of vanadate on renal cAMP levels; on the abundance of the alpha 1 isoform (${\alpha}_1$) of the Na, K-ATPase protein or its cellular localization; or on renal tissue injury. In this study, rats received a normal saline solution or vanadate (5 mg/kg BW) by intraperitoneal injection for 10 days. Levels of vanadium, cAMP, and malondialdehyde (MDA), a marker of lipid peroxidation were measured in renal tissues. Protein abundance and the localization of renal ${\alpha}_1-Na$, K-ATPase was determined by Western blot and immunohistochemistry, respectively. Renal tissue injury was examined by histological evaluation and renal function was assessed by blood biochemical parameters. Rats treated with vanadate had markedly increased vanadium levels in their plasma, urine, and renal tissues. Vanadate significantly induced renal cAMP and MDA accumulation, whereas the protein level of ${\alpha}_1-Na$, K-ATPase was suppressed. Vanadate caused renal damage, azotemia, hypokalemia, and hypophosphatemia. Fractional excretions of all studied electrolytes were increased with vanadate administration. These in vivo findings demonstrate that vanadate might suppress renal ${\alpha}_1-Na$, K-ATPase protein functionally by enhancing cAMP and structurally by augmenting lipid peroxidation.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.1
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• pp.45-53
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• 1997

In humans and many animal models with chronic progressive renal diseases, angiotensin-converting enzyme (ACE) inhibitor markedly attenuates the progression of nephropathy. Several studies have reported augmented gene expression and redistribution of renal renin in partial nephrectomized rats. Although precise mechanism(s) is not known, the renin-angiotensin system (RAS) may play an important role in the progression of renal diseases. Thus, this study was undertaken to examine the gene expression of renal renin, angiotensinogen, and $AT_1$ subtypes ($AT_{1A}$ and $AT_{1B}$) in rats with diabetic nephropathy, and the influences of lipopolysaccharide (LPS)-induced septicemia on the gene expression. Four weeks after streptozotocin (STZ) treatment (55 mg/kg, i.p.), rats were randomly divided into LPS-treated (1.6 mg/kg, i.p.) and control rats. At 6 hours after LPS treatment, the rats were killed and the kidney was removed from each rat. Northern blot and reverse transcription-polymerase chain reaction (RT-PCR)techniques were used to detect mRNA expression. STZ treatment markedly attenuated body weight gain and significantly increased blood glucose level. Renal renin content (RRC) was significantly decreased in the STZ-treated rats compared to that in control rats. The renal ACE activity between STZ-treated and control rats was not significantly different. Renal renin mRNA level was prominently increased, while angiotensinogen and $AT_{1A}$ mRNA levels were slightly decreased in STZ-treated rats compared to those in controls. $AT_1$B mRNA level did not differ in both groups. Acute LPS treatment did not show any significant changes of mRNA levels of intrarenal RAS components in both groups. These results suggest that intrarenal RAS components were differentially regulated in STZ-treated diabetic rats. Further studies are required to evaluate the relationship between intrarenal RAS and other vasomodulatory systems.

• The Korean Journal of Pharmacology
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• v.17 no.2
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• pp.31-36
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• 1981

Heavy metals which are present as trace elements in human body have been known to modify various enzymatic reaction. These metals can be essential or non-essential. Zinc, copper and calcium are essential in maintaining some biological processes, whereas non-essential metals such as cadmium, lead and mercury produce accumulatve toxic effect. Cadmium accumulated in pancreas can cause toxicity and damage of pancreatic cells, thereby influencing CHO metabolism. Lead compounds are known to produce toxic effects on the kidney, digestive system and brain fellowed by inhibition of activity of ${\rho}-aminolevulinic$ acid and biosynthesis of hemoproteins and cytochrome. Evidence has been accumulated that zinc not only acts as a cofactor in enzyme reaction but also prevents toxic effect induced by heavy metal such as copper and cadmium. To demonstrate the effect of heavy metals on pancreatic secretion, part of uncinate pancreas was taken and incubated in Krebs-Ringer bicarbonate buffer with heavy metals used. Additional treatment with CCK-OP was performed when needed. After incubation during different period of time, medium was analyzed for amylase activity using Bernfeld's method. The present study was attempted in order to elucidate the effect of several kinds of heavy metal on exocrine pancreatic secretion in vitro. The results obtained are as follows: 1) CCK-OP stimulated significantly amylase release from pancreatic fragments in vitro. 2) CCK-OP response of amylase release from pancreatic fragments was inhibited by treatmant with cadmium, especially high doses of cadmium. 3) CCK-OP response of amylase release from pancreatic fragments was inhibited when pretreated with $10^{-4}M$ copper chloride. 4) Lead chloride at the concentration of $10^{-3}M\;and\;10^{4}M$ stimulated the basal amylase release in vitro but CCK-OP response did not augment by lead chloride. 5) Zine chloride did not affect amylase release from pancreatic fragment in vitro. From the results mentioned above, it is suggested that CCK-OP response was inhibited it the amylase release from pancreatic fragments pretreated with cadmium and copper chloride.

• Journal of Nutrition and Health
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• v.34 no.4
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• pp.359-366
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• 2001

Studies were carried out to explore the influence of dietary protein level on bone metabolism in uninephrectomized rat (experimental renal failure model) when dietary Ca and P contents were equal. Male rats were uninephrectomized or sham operated and fed 8%, 15% and 40% casein diets for 24 weeks. Ca and P contents of the all diet were 0.4% and 0.6% respectively. The results are summarized as follows. We did not found any significant difference in PTH and Ca level of the serum, Ca intake and Ca excretion among the experimental groups. There was significant positive correlation between the PTH and phosphate level. There was significant inverse correlation between serum Ca and creatinine level. The effect of the dietary protein level and renal mass loss on density and Ca contents of the bone were small and different according to the kinds of the bone. Low protein diet was associated with a significant enhancement of scapular density. Femur and vertebra density, however, were not influenced by dietary protein level and uninephrectomy. Light microscopic examination showed several calcified foci in the kidney in all experimental groups. Low protein diets have been used for a long time in the conservative management of chronic renal failure as they have a beneficial effect in preventing the appearance of symptoms. This study elucidated that part of beneficial effects of the low protein diet related to the suppression of the hyperphosphatemia. And these results, even though uninephrectomized rats fed high protein diet, the secondary hyperparathyroidism is supressed by the regulation of the P level. Therefore this study emphasized the need to pay more attention to the regulation of dietary P level as well as dietary protein content in chronic renal failure. (Korean J Nutrition 34(4): 359∼366, 2001)

• The Korean Journal of Physiology
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• v.4 no.2
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• pp.33-36
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• 1970

A study was planned to see if the ginseng has any influence upon the weight of viscera of male and female rats. One hundred and ten male rats (body weight: $35{\sim}40\;gm$ at the beginning of the experiment) and an equal number of females with similar body weight were use4 Excluding 10 male and 10 females which served as controls, these rats were divided equally into 4 groups (male ginseng group, male saline group, female ginseng group and female saline group), each of which comprising 50 animals. For 45 days, the male and female ginseng groups received every day 0.6 m1/100 gm body weight of ginseng extract solution (4 mg of ginseng alcohol extract in 1 ml of saline) subcutaneously, and the male and female saline groups received the same amount of physiological saline. Each group was further divided into 5 subgroups comprising 10 animals, and the 10 control rats and each subgroups were sacrificed immediately before, and 5, 15, 35, 35, and 45 days after beginning of the drug administration, respectively. The body weight of each subgroup was checked immediately before sacrificing it, and the heart, lung, liver, kidney, adrenal gland, spleen, and testis or uterus of each animal were weighed with a torsion balance. Following results were obtained: 1. Ginseng significantly facilitated gain in weight of testis and spleen as well as body weight of rats from 35th day after beginning of the drug administration on, but not before this time. 2. Ginseng did not exert significant influence upon the weight of heart, lung, liver, tidney, adrenal gland, and uterus of the rat.

• Nutrition Research and Practice
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• v.1 no.2
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• pp.113-119
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• 2007

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.