• Toxicological Research
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• v.28 no.3
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• pp.179-185
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• 2012

Paecilomyces sinclairiis (PS) is known as a functional food or human health supplement. However concerns have been raised about its kidney toxicity. This study was performed to investigate the kidney toxicity of PS by 13 week-oral administration to rats. Blood urea nitrogen (BUN), serum creatinine, and kidney damage biomarkers including beta-2-microglobulin (${\beta}2m$), glutathione S-transferase alpha (GST-${\alpha}$), kidney injury molecule 1 (KIM-1), tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), vascular endothelial growth factor (VEGF), calbindin, clusterin, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL) and osteopontin were measured during or after the treatment of PS. BUN, creatinine and kidney damage biomarkers in serum were not changed by PS. However, kidney cell karyomegaly and tubular hypertrophy were observed dose-dependently with higher severity in males. KIM-1, TIMP-1 and osteopontin in kidney and urine were increased dose dependently in male or at the highest dose in female rats. Increased urinary osteopontin by PS was not recovered at 2 weeks of post-exposure in both genders. Cystatin C in kidney was decreased at all treatment groups but inversely increased in urine. The changes in kidney damage biomarkers were more remarkable in male than female rats. These data indicate that the PS may provoke renal cell damage and glomerular filtration dysfunction in rats with histopathological lesions and change of kidney damage biomarkers in kidney or urine. Kidney and urinary KIM-1 and cystatin C were the most marked indicators, while kidney weight, BUN and creatinine and kidney damage biomarkers in serum were not influenced.

• Journal of Nutrition and Health
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• v.30 no.7
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• pp.751-769
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• 1997

This study was performed to investigate the effect of chitosan and NOCC from different sources and of different molecular weights on cadmium toxicity. Sprague-Dawley rats were blocked into 26 groups according to body weight, and were raised for 4 weeks. Cadmium chloride was given at the level of 0 or 400 ppm in diet. Various forms of chitosan and NOCC were given at the level of 0 or 4%(w/w) of diet. Cd toxicity was alleviated by various chitosan and NOCC supplements. However, the alleviating effects were different with fiber source(crab and shrimp), type(chitosan and NOCC), and molecular weight (low, medium, and high). Molecular weight had no significant effect. Compared with shrimp-source-fiber-fed groups, crab-source-fiber-fed groups showed lower Cd concentrations in blood and kidney, lower kidney metallothionein concentration, and lower liver and kidney MT-Cd contents. Compared with NOCC -fed groups, chitosan-fed groups showed lower intestine and liver Cd concentrations, lower liver and kidney MT concentrations and MT-Cd content, and higher fecal Cd excretion. Among cadmium-exposed group, low molecular weight shrimp chitosan group showed low Cd concentrations of liver and kidney, high fecal Cd excretions, and the lowest intestine and liver MT concentrations and liver MT-Cd content. In summary, a crab source fiber was more effective than shrimp source fiber, chitosan was more effective than NOCC, and the most effective one in alleviating Cd toxicity was low molecular weight shrimp chitosan.

• Herbal Formula Science
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• v.16 no.2
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• pp.163-169
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• 2008

The kidney toxicities of BDR-29 used for improvement of the vascular diseases, was examined using male and female Sprague-Dawley rats. The male and female rats were divided into 4 groups for intragastrical treatment with doses of 0, 5, 50, and 500 mg/kg/day for 13 weeks, respectively. In all male and female rats treated with BDR-29, no mortality and gross pathological findings were shown for 13 weeks. There substantially was no change in body weight in all rats with treatment of BDR-29. The renal functional parameters including urinary volume, urine osmolality, electrolytes excretory rate, creatinine clearance, and solute-free water reabsorption were not exchanged in all rats treated with BDR-29. Taken together, these results suggest that BDR-29 has no toxicity on kidney in all male and female rats.

• Biomolecules & Therapeutics
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• v.20 no.3
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• pp.268-272
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• 2012

Nephrotoxicity occurs when kidney-specific detoxification and excretion do not work properly due to the damage or destruction of kidney function by exogenous or endogenous toxicants. Exposure to drugs often results in toxicity in kidney which represents the major control system maintaining homeostasis of body and thus is especially susceptible to xenobiotics. Understanding the toxic mechanisms for nephrotoxicity provides useful information on the development of drugs with therapeutic benefits with reduced side effects. Mechanisms for drug-induced nephrotoxicity include changes in glomerular hemodynamics, tubular cell toxicity, inflammation, crystal nephropathy, rhabdomyolysis, and thrombotic microangiopathy. Biomarkers have been identified for the assessment of nephrotoxicity. The discovery and development of novel biomarkers that can diagnose kidney damage earlier and more accurately are needed for effective prevention of drug-induced nephrotoxicity. Although some of them fail to confer specificity and sensitivity, several promising candidates of biomarkers were recently proved for assessment of nephrotoxicity. In this review, we summarize mechanisms of drug-induced nephrotoxicity and present the list of drugs that cause nephrotoxicity and biomarkers that can be used for early assessment of nephrotoxicity.

• Microbiology and Biotechnology Letters
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• v.32 no.3
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• pp.271-276
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• 2004

$\beta$-Immunan was proteoglycan obtained from mycelium of Ganoderma lucidum IY009. In this study, the protective effects of $\beta$-Immunan, against the CDDP induced in vitro cytotoxicity and in vivo renal toxicity, was measured. Concentration dependent cytotoxicities of CDDP in normal kidney cells (Vero, TCMK-l) were reduced by $\beta$-Immunan treatment. Increased renal toxicity factors, such as elevation of blood urea nitrogen (BUN) and serum creatinine, reduction of kidney weight and malonidialdehyde (MDA), by intraperitoneal administration of CDDP in rats was improved. These results indicated that $\beta$-Immunan have a protective effects against the CDDP induced renal toxicity, however, it needed to confirm the detailed mechanism for therapeutic effects.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.3
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• pp.771-775
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• 2007

Licorice has been used for cure of injuries and for detoxification in East Asia. This study investigated the protective effect of licorice water extract against cadmium (CdCl$_2$, Cd)-induced nephro-toxicity in rats. To induce acute toxicity, Cd (4 mg/kg body weight) was dissolved in normal saline and then, intravenously (i.v.) injected to animals. In experiments, animals were orally administrated with vehicle or licorice water extract (50-100 mg/kg) for 3 days, exposed to a single injection of Cd after 24 h the last licorice/vehicle treatment. Licorice protected kidney injuries by Cd treatment. The number of glomeruli showing vasodilatation and thickening of Bowman's capsule was dose-dependently decreased by licorice. These results suggest that licorice might be a potent preventive protector against Cd-induced nephro-toxicity in rats.

• Preventive Nutrition and Food Science
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• v.11 no.2
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• pp.115-119
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• 2006

The object of this study was to examine whether the germanium fortified yeast administered to SD rat is accumulated in the liver and kidney. The administration doses were within 2,000 mg/kg which is the level of NOAEL (no observed adverse effect level) proved through the previous study of single/consecutive oral toxicity test. There were no significant clinical symptoms and mortality following the administration of organic germanium-fortified yeast (0, 500, 1,000, 2,000 mg/kg) during the whole test period, and also no difference in the consumed amount of feed and water for each group. No significant abnormalities of hematology and blood chemistry parameters were found in all groups of organic germanium-fortified yeast (0, 500, 1,000, 2,000 mg/kg). The amount of germanium accumulated in liver and kidney was 0 g/kg by ICP-AES method in the group of organic germanium-fortified yeast. In the positive control group of $GeO_2$ (150 mg/kg), the amount of accumulation was shown to 3135.0 and 4277.2 g/kg in each female and male kidney and 1044.3 and 2135.8 g/kg in each female and male liver, respectively. Organic germanium-fortified yeast, a biosynthetic product resulting from putting germanium into yeast, did not show any clinical symptoms, blood chemical significance, and residues in kidney and liver. It could be inferred that the non-toxic amount of organic germanium-fortified yeast was up to 2,000 mg/kg.

• Journal of Nutrition and Health
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• v.29 no.9
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• pp.958-970
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• 1996

This study was performed to investigate the effect of dietary calcium level on cadmium and lead toxicity in rats. Fifty-four male rats of Sprague-Dawely strain weighing 152$\pm$12g were blocked into 9 groups according to body weight, and were raised for 30 days. Nine experimental diets different with cadmium(0%, 0.04%), lead (0%, 0.071%) and calcijm(0.5%, 1.0%, 1.5%) levels were prepared. The results are summarized as follow. Weight gain, F.E.R.(food efficiency ratio), and weights of liver, kidney and femur were lower in cadmium exposed groups than those of heavy metal free groups. Weight gain F.E.R. and ash weight of lead groups were lower than those of heavy metal free groups. But, these were increased with increasing dietary calcium level. Cadmium and lead concentrations in blood, liver, kidney and femur were lower in rats fed 1.5% calcium than 0.5% calcium diet. Fecal cadmium and lead excretions were remarkably increased in 1.5% calcium groups, and cadmium and lead retention rates were decreased in 1.5% calcium groups. Metallothionein concentrations in liver, kidney and small intestine were higher in rats exposed to cadmium and lead. Calcium content in blood, femur and daily urinary and fecal calcium excretion were decreased by cadmium and lead additions, and increased in 1.5% calcium groups. Creatinine clearance were decreased with cadmium administratino and calcium addition. In conclusion, weight gain and organ weights were decreased with cadmium or lead administration. But, cadmium administration was more toxic than lead adminstration. Cadmium or lead toxicity was alleviated by increasing dietary calcium level. Especially, lead toxicity was alleviated in proportion to dietary calcium level.

• Toxicological Research
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• v.35 no.2
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• pp.181-190
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• 2019

Lentinus squarrosulus (Mont.) is an edible wild mushroom with tough fruiting body that belongs to the family Polyporaceae. It is used in ethnomedicine for the treatment of ulcer, anaemia, cough and fever. Recent studies have demonstrated its anticancer, anti-diabetic and antioxidant properties. However, little or no information is available regarding the bioactive components and toxicological study of wild dried L. squarrosulus. Therefore, this study investigated the bioactive components of aqueous extract of boiled wild dried L. squarrosulus and its toxicological effects in rats. The extract of L. squarrosulus was subjected to GC-MS analysis. The acute toxicity test was performed by oral administration of a single dose of up to 5,000 mg/kg extract of L. squarrosulus. In subacute study, the rats were orally administered extract of L. squarrosulus at the doses of 500, 1,000 and 1,500 mg/kg body weight daily for 14 days. The haematological, lipid profile, liver and kidney function parameters were determined and the histopathology of the liver and kidney were examined. The GC-MS analysis revealed the presence of bioactive compounds; 1-tetradecene, fumaric acid, monochloride, 6-ethyloct-3-yl ester, 9-eicosene, phytol, octahydropyrrolo[1,2-a]pyrazine and 3-trifluoroacetoxypentadecane. In acute toxicity study, neither death nor toxicity sign was recorded. In the sub-acute toxicity study, significant differences (p < 0.05) were observed on creatinine, aspartate aminotransferase, alanine aminotransferase, total cholesterol, triglycerides and high-density lipoprotein cholesterol. Whilst no significant differences (p > 0.05) were observed on packed cell volume, heamoglobin, red blood cell, white blood cell and alkaline phosphatase, in all the tested doses. No histopathological alterations were recorded. Our findings revealed that aqueous extract of L. squarrosulus may have antimicrobial, antinocieptive and antioxidant properties based on the result of GC-MS analysis. Results of the toxicity test showed no deleterious effect at the tested doses, suggesting that L. squarrosulus is safe for consumption at the tested doses.

• Journal of Nutrition and Health
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• v.29 no.5
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• pp.461-471
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• 1996

This study was performed to investigate the effect of dietary protein and cysteine levels on cadmium toxicity in rats. Seventy-two male rats of Sprague-Dawley strain weighting 171$\pm$3g were blocked into 12 groups according to body weight, and were raised for 30 days. cadmium chloride was given at levels of 0 or 400ppm, protein at levels of 7, 15 and 40%, and cysteine was added(total dietary cysteine contents : 0.45%) to diet or not. The results are summarized as follow. Food intake, weight gain, food were lower than those of cadmium free group. But, these were increased with increasing dietary protein level and cysteine addition. Fecal cadmium excretion was remarkably increased in high protein (40%) groups. Thus, cadmium retention rates were decreased in high protein groups. Metallothionein concentrations in liver and kidney were increased in cysteine addition, and cadmium administration. Especially, these were remarkably increased in cadmium and cysteine added groups. Urinary calcium excretion was increased with cadmium administration, but urinary protein excretion and creatinine clearance were not changed in these animal. In conclusion, food intake, weight gain and organ weights were decreased with administration. Cadmium toxicity was alleviated by increasing fecal cadmium excretion, while cysteine addition increased metallothionein concentrations in liver and kidney. From these results, it was shown that cadmium toxicity was alliviated by synergistic effect of high protein level and cysteine addition.