• Journal of Food Hygiene and Safety
• /
• v.27 no.1
• /
• pp.42-49
• /
• 2012

This study was carried out to investigate the toxicity of food Red No.2 in the Sprague-Dawley (SD) female rat for 4 weeks. SD rats were orally administered for 28 days, with dosage of 500, 1,000, 2,000 mg/kg/day. Animals treated with food Red No.2 did not cause any death and show any clinical signs. They did not show any significant changes of body weight, feed uptake and water consumption. There were not significantly different from the control group in urinalysis, hematological, serum biochemical value and histopathological examination. In conclusion, 4 weeks of the repetitive oral medication of food Red No.2 has resulted no alteration of toxicity according to the test materials in the group of female rats with injection of 2,000 mg/kg. Therefore, food Red No.2 was not indicated to have any toxic effect in the SD rats, when it was orally administered below the dosage 2,000 mg/kg/day for 4 weeks.

• Korean Journal of Environmental Agriculture
• /
• v.33 no.2
• /
• pp.103-110
• /
• 2014

BACKGROUND: Azadirachta indica has been widely used as environment-friendly organic materials because of its insecticidal properties. This study was carried out to investigate the acute toxicity and the subacute toxicity of Azadirachta indica extract(AIE) in rats. METHODS AND RESULTS: For the oral acute toxicity test, Sprague-Dawley rats were gavaged with 2.0 g/Kg bw of AIE. The $LD_{50}$ value was greater than 2.0 g/Kg bw for both male and female rats. For the subacute toxicity study, rats were treated with AIE at doses of 0.5, 1.0, 2.0 mg/Kg bw once a day for 4 weeks(n=10 animals per each group). There were no significant changes in body weight, food intake and water consumption observed during the experimental duration. In addition, no difference of relative kidney weight was observed among all treated groups. Serum creatinine level in the AIE 2.0 g/Kg group increased significantly compared with that of control group in male rats, but serum blood urea nitrogen was significantly decreased in a dose-dependent manner (p<0.05). Significant increase of serum cholesterol levels were observed in all AIE groups, compared with the control group, in the female rats (p<0.05). However, histopathological examination of the kidney did not reveal any significant lesions in all groups. CONCLUSION: On the basis of results, it could be concluded that oral administration AIE didn't cause any toxic response in kidney, except the increased serum cholesterol.

• Journal of Dairy Science and Biotechnology
• /
• v.34 no.2
• /
• pp.99-116
• /
• 2016

We herein performed animal safety assessment in accordance with Good Laboratory Practice (GLP) regulations with the aim of developing sialic acid from glycomacropeptide (hereafter referred to as "GMP") as an index ingredient and functional component in functional foods. GMP is a type of whey protein derived from milk and a safe food, with multiple functions, such as antiviral activity. A test substance was produced containing 7% (w/w) sialic acid and mostly-hydrolyzed whey protein (hereafter referred to as "7%-GNANA") by enzymatic treatment of substrate GMP. The maximum intake test dose level was selected based on 5,000 mg/kg/day dose set for male NOEL (no-observed-effect-level) and female NOAEL (no-observed-adverse-effect-level) determined by a dose-range finding (DRF) test (GLP Center of Catholic University of Daegu, Report No. 15-NREO-001) that was previously conducted with the same test substance. To evaluate the toxicity of a repeated oral dose of the test substance in connection with the previous DRF study, 1,250, 2,500, and 5,000 mg/kg of the substance were administered by a probe into the stomachs of 6-week-old SPF Sprague-Dawley male and female rats for 90 d. Each test group consisted of 10 male and 10 female rats. To determine the toxicity index, all parameters, such as observation of common signs; measurements of body weight and food consumption; ophthalmic examination; urinalysis, electrolyte, hematological, and serum biochemical examination; measurement of organ weights during autopsy; and visual and histopathological examinations were conducted according to GLP standards. After evaluating the results based on the test toxicity assessment criteria, it was determined that NOAEL of the test substance, 7%-GNANA, was 5,000 mg/kg/day, for both male and female rats. No animal death was noted in any of the test groups, including the control group, during the study period, and there was no significant difference associated with test substance, as compared with the control group, with respect to general symptoms, body weight changes, food consumption, ophthalmic examination, urinalysis, hematological and serum biochemical examination, and electrolyte and blood coagulation tests during the administration period (P<0.05). As assessed by the effects of the test substance on organ weights, food consumption, autopsy, and histopathological safety, change in kidney weight as an indicator of male NOAEL revealed up to 20% kidney weight increase in the high-dose group (5,000 mg/kg/day) compared with the change in the control group. However, it was concluded that this effect of the test substance was minor. In the case of female rats, reduction of food consumption, increase of kidney weight, and decrease of thymus weight were observed in the high-dose group. The kidney weight increased by 10.2% (left) and 8.9% (right) in the high-dose group, with a slight dose-dependency compared with that of the control group. It was observed that the thymus weight decreased by 25.3% in the high-dose group, but it was a minor test substance-associated effect. During the autopsy, botryoid tumor was detected on the ribs of one subject in the high-dose group, but we concluded that the tumor has been caused by a naturally occurring (non-test) substance. Histopathological examination revealed lesions on the kidney, liver, spleen, and other organs in the low-dose test group. Since these lesions were considered a separate phenomenon, or naturally occurring and associated with aging, it was checked whether any target organ showed clear symptoms caused by the test substance. In conclusion, different concentrations of the test substance were fed to rats and, consequently, it was verified that only a minor effect was associated with the test substance in the high-dose (5,000 mg/kg/day) group of both male and female rats, without any other significant effects associated with the test substance. Therefore, it was concluded that NOAEL of 7%-GNANA (product name: Helicobactrol) with male and female rats as test animals was 5,000 mg/kg/day, and it thus was determined that the substance is safe for the ultimate use as an ingredient of health functional foods.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.16 no.1
• /
• pp.78-88
• /
• 2002

Experimental animals were divided into 5 groups; normal, cadmium control, and 3 experimental groups. Cadmium control and experimental groups were exposed to 1 mg/㎥ of cadmium aerosol in air by inhalation exposure for 6 hours/day, 5 days/week during 4 weeks. Dosages of 20, 40, and 80mg/kg of extracts of persimmon leaves were intraperitoneally injected to experimental groups respectively and several toxicological parameters and induction of metallothionein were measured from the rats that inhaled cadmium aerosol in air. The results of this study were as follows. Cadmium concentration that cadmium control and experimental groups were inhaled was 0.980±0.061 mg/㎥. Mass median diameter of cadmium aerosol for inhalation exposure was 4.93±0.483㎛. Cadmium content of normal group in lung was 0.088㎍/g and the highest cadmium content in lung, 55.492㎍/g was from 80mg/kg dose group. Cadmium concentration of normal group in blood was 0.348㎍/100㎖ and the highest cadmium concentration in blood, 2.642㎍/100㎖ was from cadmium control. Cadmium concentration of normal group in liver was 0.010㎍/g and the highest cadmium concentration in liver, 31.100㎍/g was from 20mg/kg dose group. Cadmium concentration of normal group in kidney was 0.030㎍/g and the highest cadmium concentration in kidney, 2.526㎍/g was from cadmium control. Cadmium concentration of normal group in intestine was O.064㎍/g and the highest cadmium concentration in intestine, 0.300㎍/g was from 80mg/kg dose group. The highest cadmium concentration in urine by week was 6.080㎍/day from 20mg/kg dose group in the fouth week and the highest cadmium concentration in feces by week was 341.731㎍/day from 20mg/kg dose group in the fouth week. Metallothionein concentration of normal group in lung was 5.769㎍/g and the highest in lung, 30.986㎍/g was from 80mg/kg dose group. Metallothionein concentration of normal group in liver was 38.856㎍/g and the highest in liver, 169.378㎍/g was from 40mg/kg dose group. Metallothionein concentration of normal group in kidney was 22.228㎍/g and the highest in kidney, 47.898㎍/g was from 80mg/kg dose group. Metallothionein concentration of normal group in intestine was 2.170㎍/g and the highest in intestine, 13.642㎍/g was from 80mg dose group.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.17 no.1
• /
• pp.118-122
• /
• 2003

Oxidative stress and its consequent lipid peroxidation exert harmful effects, which have been currently involved in the generation of carbon tetrachloride (CCl₄)-induced fibrosis(cirrhosis). In this study, it was investigated whether dried extract of 田螺(Concha Cipangopaludinae; CC) has liver functional improvement, antioxidative and antifibrotic effect in rats those were induced liver fibrosis by CCl₄ administration. The female Sprague-Dawley rats were divided into 3 groups(Normal, AC, AC-CC) and were observed in 6 weeks. Except for normal group, liver fibrosis(cirrhosis) in rats were developed by CCl₄ administration(0.8 ㎖/rat/week). And the rats were treated with prepared CC(p. o. 2 ㎖/day/rat). At the time of sacrifice, the liver, kidney and spleen were weighed and the ratio of organ weight/body weight was calculated. The MDA, hyp and biochemical parameters(AST, ALT, ALP, t-bili) were measured in sera and liver tissue of rats. The strong yellow color of urine was observed in all CCl₄-treated group compared with normal group, but jaundice didn't appear in CCl₄-treated group. The mortality of CCl₄-treated group is very low(<13%) during 6 weeks of observation time. The ratio of liver/body as well as the weight of liver in CCl₄-treated rats significantly increased compared with that in normal group(p<0.001). The level of clinical parameters in sera of all liver fibrosis(cirrhosis) developed rats were significantly higher than that of normal group(p<0.001-0.05). Especially the value of BUN, ALP, t-bilirubin in AC-CC group showed 20.9%, 19.6%, 47.9% lower than that in AC group. The content of hyp in CCl₄-treated rats was significantly higher than normal group(p<0.001～<0.05), and showed 12.2% lower value in the AC-CC group than AC group(p<0.05). The production of lipid peroxidation(MDA) in sera and liver tissue significantly increased under the fibrotic(cirrhotic) condition(p<0.001～<0.05). Especially the MDA value of AC-CC group in sera significantly 46.5% decreased compared with that of AC group(p<0.05), and the MDA value of AC-CC in liver tissue showed 21.4% lower than that of AC group. Concha Cipangopaludinae can be improved hepatic function, and maybe have effect of liver protection, antioxidation and antifibrosis.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.18 no.3
• /
• pp.868-873
• /
• 2004

Renal dysfunction could be developed as the secondary disease of liver cirrhosis. Delayed or suppresed lipid peroxidation by the treatment with physiological active substances could be explained as the antioxidative and protective effect in tissue damage. In this study, we investigated an antioxidative effect and renal function improvement of Hovenia dulcis in liver fibrosis(cirrhosis) induced rats. The female Sprague-Dawley rats (180∼210 g) were divided into 3 groups (Normal, AC: CCl₄ mixture treated group, AC-HV: CCl₄ mixture+ Hovenia dulcis treated group) and renal damage was developed by CCl₄ mixture administration in 4 weeks (0.8 ㎖/rat). The tissue of kidney and liver and sera were used for quantitative measurement of enzyme activity, MDA and Hyp. The histological change and gene expression of collagen α1(III) mRNA and a1(IV) mRNA were observed by Masson's trichrome staining and RT-PCR. As a result, the clinical biochemical parameters of liver function (AST and ALT) in sera of AC-HV group showed significantly 46.4% and 104.8% lower (p<0.005), and the level of ALP and BUN as the parameter of protein urine and azotemia showed 17.8 % and 25.8 % lower than in AC group. In AC-HV group, the concentration of MDA in kidney and liver was decreased significantly 15.8% and 21.3% when compared with AC group (p<0.01 -0.005). The content of Hyp in kidney of AC-HV group is merely higher than in AC group, in contrast to liver tissue. The expression of collagen α1(III) mRNA and collagen α1(IV) mRNA was decreased in AC, but both of collagen mRNA in normal and AC-HV group expressed fast similar. More massive lipid droplets, thicker collagen fiber bundles in portal triads and more formation of portal central septum were observed in the liver of AC group than in AC-HV group. In conclusion, CCl₄ mixture intoxication could be developed not only liver fibrosis(cirrhosis) but also renal dysfunction by the massive lipid peroxidation and suppression of interstitial collagen and basement membrane collagen synthesis. And the water extract of Hovenia dulcis may be possessed the antioxidative and protective effect and improvement of kidney function in renal dysfunction induced rats.

• Korean Journal of Veterinary Research
• /
• v.35 no.4
• /
• pp.793-807
• /
• 1995

This study was carried out to investigate the effects of diethyl maleate(DEM) on the carcinogenesis of forestomach and pyloric glandular stomach in rats caused by N-methyl-N'-nitro-N-nitrosoguanidine(MNNG). A total of 60 male 6-week-old Wistar rats were given twice intragastric injection of MMNG(200mg/kg BW), then were given diets containing 5% NaCl for 3 weeks until 4th week of the experiment. And then the animals of groups of 1 and 2 were placed on diets containing 0.2% DEM for 16 weeks until the end of 20 weeks of the experiment. On the other hand, the animals of groups of 3 and 4 were placed on basal diets for the same periods. The tissues of forestomach and liver of each group were frozen in liquid nitrogen and the activities of quinone reductase(QR) were determined by measurement of the dicoumarol-sensitive reduction of dichloro-indophenol by NADPH at 600nm. All rats were sacrificed at the end of 20 weeks of the experiment. Every animal was fasted for 24 hrs prior to sacrifice. The forestomach was fixed in 10% neutral phosphate buffered formalin for histology and the pyloric gland was fixed in sublimated formalin for immunohistochemistry of pepsinogen 1 altered pyloric gland(PAPG). The final body weight of the group given MNNG and treated with 5% NaCI and DEM was significantly decreased compared with that of the group 4(p<0.05). Food and water consumption rates were not significantly changed. The preneoplastic and neoplastic lesions of the forestomach given MNNG and treated with 5% NaCI and DEM were significantly increased compared to those of the group 4(p<0.0l). The incidence of PAPG in the groups treated with 0.2% DEM was significantly increased compared with that of the group 4(group 1:p<0.01, group 2:p<0.05). The activities of QR of forestomach in the groups treated with 0.2% DEM were significanitly increased compared with those of the group 4(p<0.001), but those of liver were not significant. These results indicate that DEM exert the enhancing effect of forestomach and glandular stomach carcinogenesis in rats pretreated with MNNG and NaCl.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.26 no.5
• /
• pp.724-731
• /
• 2012

This study was designed to elucidate whether combination with Korean red ginseng and Morus alba L. (MPM), traditional treatment for diabetes, ameliorates on high fructose-induced steatohepatitis and vascular inflammation. Animals were divided into four groups; Control receiving tap water, fructose-fed, rosiglitazone-treated fructose-fed rats, and MPM-treated fructose-fed rats both receiving supplemented with 60% fructose (n=10). The MPM or rosiglitazone groups initially received a high-fructose diet alone for 8 weeks, with supplementation with MPM or rosiglitazone, peroxisome proliferators-activated receptor gamma ($PPAR{\gamma}$) agonist, occurring during the final 6 weeks. Treatment with MPM significantly prevented the increase in c-reactive protein (CRP) levels in the high fructose group. MPM suppressed high fructose diet-induced vascular inflammation marker expression such as intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. MPM also reduced intima/media thickness of thoracic aorta. Histologic observation and oil red O staining demonstrated hepatic tissue damage and lipid accumulation were severe in high fructose group. Treatment with MPM ameliorated hepatic tissue morphology with minimized steatosis. In addition, MPM attenuated hepatitis by inhibition of monocyte chemoattractant protein-1 (MCP-1) expression. MPM-fed group showed lower serum GOT and GPT levels comparing with high fructose group. MPM and rosiglitazone (positive control) significantly decreased the size of epididymal adipocytes. Taken together, the administration of MPM inhibited high fructose-induced steatohepatitis and vascular inflammation. These results suggested that MPM is useful in the prevention or treatment of metabolic syndrome-related disorders such as fatty acid metabolism and vascular homeostasis.

• The Korean Journal of Pesticide Science
• /
• v.15 no.3
• /
• pp.278-288
• /
• 2011

This study was conducted to evaluate the safety of ${\beta}$-carotene biofortified rice, a genetically modified organism (GMO) developed by Rural Development Administration. ${\beta}$-carotene biofortified rice were exposed on Sprague-Dawley rats for 13 weeks. All rats survived until the end of the exposure period. There were no biologically significant differences in body weight, feed and water consumption, weight gains and feed efficiency. There were no clinical signs of toxicity attributable to exposure to GM rice. Mild decreases in AST, ALT, TG levels were observed in Group II (25% GM rice (w/w) and Group III (50% GM rice (w/w), both in females and males. Results of histopathological changes treated with the ${\beta}$-carotene biofortified rice had no significant differences between the control and treatment groups. Based on these results, we deemed that genetically modified ${\beta}$-carotene biofortified rice was as safe as conventional rice.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.16 no.3
• /
• pp.547-552
• /
• 2002

To investigate an efficacy of mixed extract with Ginseng radix, Puerariae lobata, Puerariae radix, Rubi pructus, Gomi pructus, Hoelen, Dried orange peel and Parvum comus cervi etc., on the hangover elimination, 12 hr-fasted male Sprague-Dawley rats weighing 150-200 g were given mixed extract (5 mL/kg, p.o.) and administered ethanol at a dose of 3 g/kg bw (25% in distilled water) orally 30 min postdosing. Blood was collected from caudal artery at 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12hr and then the animals were sacrificed at 24hr after the ethanol treatment. In these experiments, liver function indices, such as alanine aminotransferase and alkaline phosphatase activities, showed unaltered results in all treated groups compared with the normal group. The pharmacokinetics of ethanol after oral administration of mixed extract were also evaluated. From 0 min to 12hr, the administration of mixed extract showed 14% reduction of the area under the serum concentrations-versus-time curves (AUC) compared with the control group. The activities of alcohol dehydrogenase and aldehyde dehydrogenase measured at 24hr postdosing were also not altered by the administration of mixed extract compared with the control group. These studies demonstrate that oral administration of mixed extract, prepared by traditional prescription, decreases the ethanol concentration in serum and reduces AUC, suggesting that the mixed extract is effective for elimination of ethanol-induced hangover.