• Korean Journal of Food Science and Technology
• /
• v.52 no.5
• /
• pp.555-559
• /
• 2020

In order to examine the toxicity of palatinose-L (Pal-L) bioconverted from sucrose, we performed a 14-consecutive day toxicity study with male and female Sprague-Dawley (SD) rats. We recorded clinical signs of toxicity, body weight, organ weights, hematology, blood biochemical, urinalysis, histological changes in organs, such as the liver and kidneys, and clinical chemistry analysis data for all SD rats. There were no significant changes in food/water consumption, body weight, and organ weights during the experimental period. Although there were some hematologic and urinalysis alterations, these changes were not considered toxicologically significant. In addition, histopathological examination of the liver and kidneys revealed no abnormal or toxicological changes between the control and Pal-L-treated rats of both sexes. Collectively, these results suggest that Pal-L was not indicated to have any toxicity in the SD rats when it was orally administered up to a dose of 1,000 mg/kg/day for 14 days.

• Biomolecules & Therapeutics
• /
• v.19 no.1
• /
• pp.38-44
• /
• 2011

Cisplatin is widely used for various types of cancers. However, its side effects, most notably, renal toxicity often limit its clinical utility. Although previous metabolomic studies reported possible toxicity markers, they used small number of animals and statistical approaches that may not perform best in the presence of intra-group variation. Here, we identified urinary biomarkers associated with renal toxicity induced by cisplatin using NMR-based metabolomics combined with Orthogonal Projections to Latent Structures-Discriminant Analysis (OPLS-DA). Male Sprague-Dawley rats (n=22) were treated with cisplatin (10 mg/kg single dose), and the urines obtained before and after treatment were analyzed by NMR. Multivariable analysis of NMR data presented clear separation between non-treated and treated groups. The OPLS-DA statistical results revealed that 1,3-dimethylurate, taurine, glucose, glycine and branched-chain amino acid (isoleucine, leucine and valine) were significantly elevated in the treated group and that phenylacetylglycine and sarcosine levels were decreased in the treated group. To test the robustness of the approach, we built a prediction model for the toxicity and were able to predict all the unknown samples (n=14) correctly. We believe the proposed NMR-based metabolomics with OPLS-DA approach and the resulting urine markers can be used to augment the currently available blood markers.

• The Korea Journal of Herbology
• /
• v.33 no.4
• /
• pp.101-108
• /
• 2018

Objectives : This study aimed to effects antioxidant activity of citrus peel extract (CPE) and effect on its glucose metabolism in L6 rat skeletal muscle cells. Methods : Antioxidative activities were evaluated by using 10 kinds of natural materials, and total polyphenol and flavonoid contents were examined. The L6 muscle cells toxicity of CPE was examined by MTT assay. Expression of glucose-related genes in L6 muscle cells by CPE treatment was analyzed by real-time PCR and western blotting. Results : The $IC_{50}$ values of DPPH and ABTS free radical scavenging activity of CPE were ($15.47{\pm}0.26{\mu}g/m{\ell}$ and $12.07{\pm}1.23{\mu}g/m{\ell}$, respectively), effectively clearing DPPH and ABTS. CPE showed total polyphenol and flavonoid contents ($20.30{\pm}0.38$ and $64.20{\pm}0.52$, respectively). The selected CPE were used in experiments using an effective concentration that is not toxic in L6 muscle cells. We investigated insulin receptor substrate-1 (IRS-1), phosphatidylinositol 3-kinase regulatory (PI3KR), Akt, and glucose transporter 4 (GLUT4). mRNA analysis by realtime PCR showed no significant difference, but CPE-treated cells showed a tendency to increase in concentration-dependent manner. However, analysis of protein expression of Akt and GLUT4 by western blotting showed that CPE treatment significantly increased concentration dependent (p<0.001). Conclusions : As a result, citrus peel extract with high antioxidant activity regulates glucose metabolism in L6 muscle cells. Therefore, CPE can be a potential treatment for the treatment of diabetes.

• Korean Journal of Pharmacognosy
• /
• v.29 no.4
• /
• pp.379-383
• /
• 1998

Sodium arsenate and Paljin-Tang extract (PJT), a herbal restorative were treated p.o. 20 mg/kg and 500 mg/kg, respectively, and concurrently to rats, and examined the biochemical parameters in blood. The values of white blood cell (WBC), red blood cell (RBC), hemoglobin (Hgb) and hematocrit (Hct) in each group did not show significant variance. The value of aspartate aminotrasferase(AST) of arsenic-treated group was increased for 2 weeks significantly while that of the group of concurrent administration with PJT became low significantly compared with arsenic-treated group and the value of alkaline phosphatase (ALP) of arsenic-treated group was decreased while that of the group of concurrent administration with PJT was increased significantly compared with arsenic-treated group. The value of glucose (Glu) was increased and those of lactic dehydrogenase (LDH), blood urea nitrogen (BUN) and triglyceride (TG) were decreased at first but increased later while the group of concurrent administration with PJT showed significant recovery from the toxicity of arsenic.

• Journal of Aquaculture
• /
• v.18 no.3
• /
• pp.196-199
• /
• 2005

Farmed red sea breams, Pagrus major, were fed for 60 days with pellets containing different concentrations of benzo(a)pyrene (0, 0.2, 2, 20 mg/kg) to generate a biomarker of the chemical toxicity in the fish. The fish exposed to the chemical concentrations did not show any significant difference in the weight gain, conditioning, factor, and hepatosomatic index. However, some haematological parameters, such as glucose, calcium, magnesium, GOT (glutamic oxalate transaminase), and GPT (glutamic pyruvate transaminase) were influenced by the chemical exposure. Of them, two enzymes, GOT and GPT, increased significantly 60 days after the exposure in a way of concentration dependence (P<0.05). In the study of ecotoxicological biomarker, sensitivity to adverse environments is one of the key available factors. The fish changes in GOT and GPT were an earlier and reliable sign of the fish response against the chemical exposure, rendering the two enzymatic factors as a useful biomarker at least to benzo(a)pyrene exposure in the farming waters.

• YAKHAK HOEJI
• /
• v.36 no.1
• /
• pp.80-86
• /
• 1992

Streptozotocin (STZ) is a naturally occurring nitrosoamide used extensively to produce diabetes in experimental animals. Our previous study has demonstrated that i.v. administraton of streptozotocin induces significant red blood cell hemolmysis in rats. Since it has been reported that the highest concentration of STZ is found in the liver, the effect of STZ in freshly isolated rat hepatocytes has been investigated. STZ treatment (10 mM) did not cause significant loss of viability throughout 4 hour incubation, while high dose of STZ (300 mM) to hepatocytes resulted in complete cell death within 3 hours. Addition of 40 mM glucose to incubation medium did not potentiate STZ-induced hepatotoxicity, suggesting that STZ-induced hyperglycemia in vivo did not affect its hepatotoxicity. To investigate the mechanixm of the toxicity, intracellular total glutathione level was determined. Tratment with 10 mM STZ which was not toxic to hepatocytes led to complete depletion of intracellular glutathione level within 1 hour incubation. These results suggest that STZ-induced hepatotoxicity may be independent on the intracellular glutathione depletion.

• Archives of Pharmacal Research
• /
• v.22 no.6
• /
• pp.565-570
• /
• 1999

DW2282,(S)-(+)-4-phenyl-1-[1-(4-aminobenzoyl)-indoline-5-sulfonyl]-4,5-dihydro-2-imidazolone hydrochloride, is a new anticancer agent which is thought to exhibit a characteristic mechanism of action in the inhibition of tumor growth. In this study, we estimated the toxicities of DW2282 in mice. When mice were orally dosed for five consecutive days at the dosages of 50, 100 and 150 mg/kg, DW2282 did not induced methemoglobinemia and hypoglycemia at any of these doses. However, increased ALT and AST values were observed in the 150 mg/kg dosing group, and white blood cells (WBC) were significantly decreased at all doses. However, the changes in WBC count, ALT and AST immediately reversed after the cessation of drug administration. In addition, we found that DW2282 did not cause an increase in hemolysis in human blood. Taken together, these data suggested that DW2282 may have a relatively low level of toxicity, and that there may be a quick recovery from any toxicity it dose produce.

• Journal of Environmental Health Sciences
• /
• v.22 no.4
• /
• pp.91-101
• /
• 1996

Exposure indices are important tools which enable scientists to reliably predict and detect exposures to xenobiotics and resultant cell injury. Since the de novo synthesis of stress proteins can be detected early after exposure to some agents, analysis of toxicant-induced changes in gene expression, i.e. alterations in patterns of protein synthesis, may be useful to develop as biomarkers of exposure and toxicity. The acute and chronic effects of cadmium(Cd, $CdCl_2$ 20 mg/kg) on Wistar male rats were evaluated concerning cadmium contents, tissues enzyme activity, HSP expression. The results of the study were as follows: 1. Less cadmium was absorbed through the digestive tracts, but the ratio of contents in renal to hepatic cadmium was higher at 8 weeks after treatment. 2. ALT(alanine aminotransferase), AST(aspartate aminotransferase), glucose, BUN(blood urea nitrogen), creatinine, the key indices of the clinical changes in hepatic and renal function were significantly changed by the cadmium treatment after 1 week in liver, after 4 weeks in kidney. 3. Enhanced synthesis of 70 KDa relative molecular mass proteins were detected in 2 hours after cadmium exposure, with maximum activity occurring at 8~48 hours. Induction of $HSP_{70}$ was evident at proximal tubules and glomeruli in kidney. Testicular cells produced enough HSP to be detected normally. From the above results, it could be concluded that $HSP_{70}$ induction by the cadmium treatment was a rapid reaction to indicate the exposure of xenobiotics.

• The Korean Journal of Pharmacology
• /
• v.29 no.2
• /
• pp.283-295
• /
• 1993

Pt-complexes is currently one of the most compounds used in the treatment of solid tumors. However, its used is limited by severe side effects such as renal toxicity. Our platinum-based drug discovery program is aimed at developing drugs capable of diminishing toxicity and improving antitumor activity. We synthesized new Pt (II) complex analogues containing 1, 2-diaminocyclohexane (dach) as carrier ligand and 1, 3-bis (diphenylphosphino) propane (DPPP)/1,2-bis (diphenylphosphino) ethane (DPPE) as a leaving group. Furthermore, nitrate was added to improve the solubility. A new series of (KHPC-001) [Pt (trans-1-dach)(DPPP)] $2NO_3$ and (KHPC-002) [Pt (trans-1-dach)(DPPE)] $2NO_3$ were synthesized and characterized by their elemental analysis and by various spectroscopic techniques [infrared (IR), $^{13}carbon$ nuclear magnetic resonance (NMR)]. KHPC-001 and KHPC-002 demonstrated acceptable antitumor activity aganist P-388, L-1210 lymphocytic leukemia cells and significant activity as compared with that of cisplatin. The toxicity of KHPC-001 and KHPC-002 was found quite less than that of cisplatin using MTT, $[^3H]$ thymidine uptake and glucose consumption tests in rabbit proximal tubule cells and human kidney cortical cells.

• Toxicological Research
• /
• v.24 no.4
• /
• pp.307-314
• /
• 2008

The present study was carried out to investigate the potential adverse effects of 1,3-dichloro-2-propanol on pregnant dams after maternal exposure during the gestational days (GD) 6 through 19 in Sprague-Dawley rats. The tested chemical was administered orally to pregnant rats at dose levels of 0, 10, 30, or 90 mg/kg/day. During the test period, clinical signs, mortality, body weights, food consumption, serum biochemistry, gross findings, organ weights, and Caesarean section findings were examined. In the 90 mg/kg group, decreases in the body weight gain and food consumption, and increases in the weights of liver and adrenal glands were observed. Serum biochemical investigations revealed increases in aspartate aminotransferase (AST), alanine aminotransferase (ALT), cholesterol (CHO), triglyceride (TG), alkaline phosphatase (ALP), and bilirubin (BIL) and decreases in glucose (GLU), albumin (ALB) and total protein (TP). In the 30 mg/kg group, a decrease in the food consumption and an increase in the liver weight were observed. Serum biochemical investigation also showed increases in CHO and TG and a decrease in glucose. Since there were no signs of maternal toxicity in the 10 mg/kg group, it is considered to be the no-observed-adverse-effect level (NOAEL) of 1,3-dichloro-2-propanol. It is concluded that successive oral administration of 1,3-dichloro- 2-propanol to pregnant rats for 14 days may cause significant toxicities in body weight and liver at a dose rate ${\geq}$ 30 mg/kg/day.