1.Subchronic Oral Toxicity Evaluation of Sodium Dehydroacetate: A 90-day Repeated Dose Study in Rats.
Jin FANG ; Hai Bo LIU ; Yuan ZHI ; Yong Quan FENG ; Hui Ling WANG ; Wen Ming CUI ; Ji Yue ZHANG ; Hua Li WANG ; Zhou YU ; Xu Dong JIA
Biomedical and Environmental Sciences 2022;35(4):296-311
Objective:
The present study was undertaken to evaluate the subchronic oral toxicity of sodium dehydroacetate (DHA-Na) and to determine the point of departure (POD), which is a critical factor in the establishment of an acceptable dietary intake.
Methods:
DHA-Na was administered once daily by gavage to Sprague-Dawley rats at dose levels of 0.0, 31.0, 62.0, and 124.0 mg/kg BW per day for 90 days, followed by a recovery period of 4 weeks in the control and 124.0 mg/kg BW per day groups. The outcome parameters were mortality, clinical observations, body weights, food consumption, hematology and clinical biochemistry, endocrine hormone levels, and ophthalmic, urinary, and histopathologic indicators. The benchmark dose (BMD) approach was applied to estimate the POD.
Results:
Significant decreases were found in the 62.0 and 124.0 mg/kg BW groups in terms of the body weight and food utilization rate, whereas a significant increase was found in the thyroid stimulating hormone levels of the 124.0 mg/kg BW group. Importantly, the 95% lower confidence limit on the BMD of 51.7 mg/kg BW was modeled for a reduction in body weight.
Conclusion
The repeated-dose study indicated the slight systemic toxicity of DHA-Na at certain levels (62.0 and 124.0 mg/kg BW) after a 90-day oral exposure.
Animals
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Body Weight
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Organ Size
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Pyrones
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Rats
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Rats, Sprague-Dawley
2.Protective effect of diallyl disulfide on cyclophosphamide-induced testicular toxicity in rats.
Sung Hwan KIM ; In Chul LEE ; Hyung Seon BAEK ; Changjong MOON ; Sung Ho KIM ; Jong Choon KIM
Laboratory Animal Research 2013;29(4):204-211
This study investigated the protective effects of diallyl disulfide (DADS) against cyclophosphamide (CP)-induced testicular toxicity in male rats. DADS was gavaged to rats once daily for 3 days at 100 mg/kg/day. One hour after the final DADS treatment, the rats were given a single intraperitoneal dose of 150 mg/kg CP. All rats were killed and necropsied on day 56 after CP treatment. Parameters of testicular toxicity included reproductive organ weight, testicular sperm head count, epididymal sperm motility and morphology, epididymal index, and histopathologic examinations. The CP treatment caused a decrease in body weight, testicular sperm head count, epididymal sperm motility, and epididymal index. The histopathological examination revealed various morphological alterations, characterized by degeneration of spermatogonia/spermatocytes, vacuolization, and decreased number of spermatids/spermatocytes in the testis, and cell debris and mild oligospermia in the ductus epididymis. In contrast, DADS pretreatment effectively attenuated the testicular toxicity caused by CP, including decreased sperm head count, epididymal sperm motility, and epididymal index and increased histopathological alterations in the testis and epididymis. These results indicate that DADS attenuates testicular toxicity induced by CP in rats.
Animals
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Body Weight
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Cyclophosphamide
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Epididymis
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Humans
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Male
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Oligospermia
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Organ Size
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Rats*
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Sperm Head
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Sperm Motility
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Testis
3.Reference Data of the Main Physiological Parameters in Control Sprague-Dawley Rats from Pre-clinical Toxicity Studies.
Zhong Ze HAN ; Hong De XU ; Kwang Ho KIM ; Tae Hwan AHN ; Jin Sook BAE ; Ji Young LEE ; Ki Hyun GIL ; Joo Young LEE ; Su Jung WOO ; Hyun Jung YOO ; Hyun Kul LEE ; Kap Ho KIM ; Chan Koo PARK ; Hu Song ZHANG ; Si Whan SONG
Laboratory Animal Research 2010;26(2):153-164
The purpose of this paper is to provide reference data related to the body weight, food & water consumptions, urinalysis, hematology and serum biochemistry parameters and absolute & relative organ weights obtained from control Sprague-Dawley rats, used in the 4-week and 13-week repeated-dose toxicity studies conducted in our laboratory between 2005 and 2008. The mean, standard deviation, minimum and maximum range values for hematology and serum biochemistry parameters, data of absolute & relative organ weights, and the difference between sexes and study duration of week 4 versus 13 week are presented. The studies were conducted according to "the standards of Toxicity Study for Medicinal Products" (2005) and The KFDA Notification No. 2000-63 'Good Laboratory Practice (GLP)' (2000) issued by KFDA. These data could be used as reference material of Sprague-Dawley rats by conducting the studies to evaluate the toxicological profile of pre-clinical toxicity studies.
Biochemistry
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Body Weight
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Hematology
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Organ Size
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Rats, Sprague-Dawley
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Urinalysis
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Water
4.Anthropometric Study of the Stomach.
Eun Gyeong LEE ; Tae Han KIM ; Yeon Ju HUH ; Yun Suhk SUH ; Hye Sung AHN ; Seong Ho KONG ; Hyuk Joon LEE ; Woo Ho KIM ; Han Kwang YANG
Journal of Gastric Cancer 2016;16(4):247-253
PURPOSE: The aim of this study was to establish an anthropometric reference of the stomach for gastric cancer surgery and a modeling formula to predict stomach length. MATERIALS AND METHODS: Data were retrieved for 851 patients who underwent total gastrectomy at the Seoul National University Hospital between 2008 and 2013. Clinicopathological data and measurements from a formalin-fixed specimen were reviewed. The lengths (cm) of the greater curvature (GC) and lesser curvature (LC) were measured. Anthropometric data of the stomach were compared according to age, body weight, height (cm), and body mass index. To predict stomach length, two multiple regression analyses were performed. RESULTS: The mean lengths of the GC and LC were 22.2±3.1 cm and 16.3±2.6 cm, respectively. The men’s GC length was significantly greater than the women’s (22.4±3.1 cm vs. 21.2±2.9 cm, P=0.003). Patients aged >70 years showed significantly longer LC than those aged <50 years (16.9±2.9 cm vs. 15.9±2.4 cm, P=0.002). Patients with body weights >70 kg showed significantly longer GC than those with body weights <55 kg (23.0±2.9 cm vs. 21.4±3.2cm, P<0.001). In the predicted models, 4.11% of the GC was accounted for by age and weight; and 4.94% of the LC, by age, sex, height, and weight. CONCLUSIONS: Sex, age, height, and body weight were associated with the length of the LC, while sex and body weight were the only factors that were associated with the length of the GC. However, the prediction model was not sufficiently strong.
Body Mass Index
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Body Weight
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Gastrectomy
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Humans
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Organ Size
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Seoul
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Stomach Neoplasms
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Stomach*
5.The Effect of Rice Germ Oil Supplement on Serum and Hepatic Lipid Levels of Streptozotocin-Induced Diabetic Mice.
Sung Hyeon LEE ; Hye Kyung CHUN ; Yeon Sook LEE
The Korean Journal of Nutrition 2003;36(6):543-548
This study was carried out to investigate the effects of rice germ oil supplement on the lipid metabolism of insulin-dependent diabetic mice. Streptozotocin-induced diabetic mice were fed three kinds of experimental diets with 20% lipid, composed of 20% lard (L) : 10% lard and 10% rice germ oil (LRGO) ; and 20% rice germ oil (RBO), respectively, for 7 weeks. Diet intake, body weight, organ weight and lipid levels of serum, liver and feces were measured. There was no significant difference in diet intake, body weight and organ weight among the experimental groups. But the concentrations of serum triglyceride in the LRGO and RGO groups, and of serum total cholesterol in the RGO group, were significantly lower than those of the L group fed the 20% lard diet. The levels of hepatic total lipid of the RGO group, and of hepatic total cholesterol of the LRGO and RGO groups were significantly lower than those of the L group. The contents of total lipid and total cholesterol excreted in the feces of the LRGO and RGO groups were higher than those of the L group. These results suggest that rice germ oil can reduce the levels of total cholesterol concentrations in the serum or livers of insulin-dependent diabetic mice, and that the hypolipidemic effect of rice germ oil may be due to increasing fecal lipid excretion and decreasing lipid absorptivity.
Animals
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Body Weight
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Cholesterol
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Diet
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Feces
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Lipid Metabolism
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Liver
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Mice*
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Organ Size
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Triglycerides
6.Supplementary Effect of gamma-Oryzanol on Lipid Metabolism in Diabetic KK Mice.
Sung Hyeon LEE ; Hye Kyung CHUN ; Hong Ju PARK ; Yeon Sook LEE
The Korean Journal of Nutrition 2004;37(5):347-351
This study was carried out to investigate the supplementary effects of gamma-oryzanol extracted from rice bran on lipid metabolism in diabetic mice. We supplied 2 kinds of experimental diets (CO without and GO with 0.2% gamma-oryzanol) to diabetic mice for 8 weeks. Diet intake, body weight, organ weight, contents of serum and hepatic lipid profiles, and fecal lipid levels were measured. Though there was no significant difference in diet intake, body weight change and organ weight between experimental groups, the concentration of serum total cholesterol and hepatic total lipid, total cholesterol and HMG-CoA reductase activity was significantly lower in GO group treated with 0.2% gamma-oryzanol of diet than CO group after supplementary period of experimental diets. And total lipid, triglyceride, total cholesterol, and bile acid levels excreted to feces were significantly higher in GO group than CO group. These results suggest that gamma-oryzanol decrease the serum and hepatic lipid levels by lowing HMG-CoA reductase activity or increasing the contents of fecal lipid in diabetic KK mice.
Animals
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Bile
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Body Weight
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Body Weight Changes
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Cholesterol
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Diet
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Feces
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Lipid Metabolism*
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Mice*
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Organ Size
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Oxidoreductases
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Triglycerides
7.alpha-Lipoic acid reduced weight gain and improved the lipid profile in rats fed with high fat diet.
Eun Young SEO ; Ae Wha HA ; Woo Kyoung KIM
Nutrition Research and Practice 2012;6(3):195-200
The purpose of this study was to investigate the effects of alpha-lipoic acid on body weight and lipid profiles in Sprague-Dawley rats fed a high fat diet (HFD). After 4 weeks of feeding, rats on the HFD were divided into three groups by randomized block design; the first group received the high-fat-diet (n = 10), and the second group received the HFD administered with 0.25% alpha-lipoic acid (0.25LA), and the third group received the high-fat diet with 0.5% alpha-lipoic acid (0.5LA). The high fat diet with alpha-lipoic acid supplemented groups had significantly inhibited body weight gain, compared to that in the HFD group (P < 0.05). Organ weights of rats were also significantly reduced in liver, kidney, spleen, and visible fat tissues in rats supplemented with alpha-lipoic acid (P < 0.05). Significant differences in plasma lipid profiles, such as total lipids, total cholesterol, triglycerides, low-density lipoprotein, and high-density lipoprotein, were observed between the HFD and 0.5LA groups. The atherogenic index and the plasma high density lipoprotein-cholesterol/total cholesterol ratio improved significantly with alpha-lipoic acid supplementation in a dose-dependent manner (P < 0.05). Total hepatic cholesterol and total lipid concentration decreased significantly in high fat fed rats supplemented with alpha-lipoic acid in a dose-dependent manner (P < 0.05), whereas liver triglyceride content was not affected. In conclusion, alpha-lipoic acid supplementation had a positive effect on weight gain and plasma and liver lipid profiles in rats.
Animals
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Body Weight
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Cholesterol
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Diet, High-Fat
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Kidney
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Lipoproteins
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Liver
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Organ Size
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Plasma
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Rats
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Rats, Sprague-Dawley
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Spleen
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Thioctic Acid
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Triglycerides
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Weight Gain
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Weight Loss
8.Effects of chronic partial sleep deprivation on growth and learning/memory in young rats.
Fan JIANG ; Xiao-Ming SHEN ; Sheng-Hui LI ; Mao-Long CUI ; Yin ZHANG ; Cheng WANG ; Xiao-Gang YU ; Chong-Huai YAN
Chinese Journal of Contemporary Pediatrics 2009;11(2):128-132
OBJECTIVEThe effects of sleep deprivation on the immature brain remain unknown. Based on a computer controlled chronic sleep deprivation animal model, the effects of chronic partial sleep deprivation on growth, learning and memory in young rats were explored.
METHODSTwelve weaned male Spraque-Dawley rats (3-week-old) were randomly divided into sleep deprivation, test control and blank control groups. Sleep deprivation was performed using computer-controlled "disc-over-water" technique at 8-11 am daily, for 14 days. The temperature and weights were measured every 7 days. Morris water maze was used to test spatial learning and memory abilities before and 7 and 14 days after sleep deprivation. After 14 days of sleep deprivation, the rats were sacrificed for weighting their major organs.
RESULTSAfter 14 days of sleep deprivation, the rats' temperature increased significantly. During the sleep deprivation, the rate of weight gain in the sleep deprivation group was much slower than that in the test control and blank control groups. The thymus of the rats subjected to sleep deprivation was much lighter than that of the blank control group. After 7 days of sleep deprivation, the rats showed slower acquisition of reference memory, but were capable of successfully performing the task by repeated exposure to the test. Such impairment of reference memory was not seen 14 days after sleep deprivation.
CONCLUSIONSChronic sleep deprivation can affect growth of immature rats, as well as their abilities to acquire spatial reference memory.
Animals ; Body Temperature ; Body Weight ; Growth ; Learning ; Male ; Memory ; Organ Size ; Rats ; Rats, Sprague-Dawley ; Sleep Deprivation ; physiopathology ; psychology
9.Historical control data from 13-week repeated toxicity studies in Crj:CD (SD) rats.
Jung Min LEE ; Min Ah LEE ; Hyeon Nam DO ; Yun Ik SONG ; Re Ji Na BAE ; Hye Yeong LEE ; Sun Hee PARK ; Jin Seok KANG ; Jong Koo KANG
Laboratory Animal Research 2012;28(2):115-121
Reference ranges of standard experimental parameters are useful for comparisons in toxicology. The aim of this study was to collect data from 13-week repeated toxicity studies in Crl:CD (SD) rats, a strain widely used for toxicity and efficacy research, for establishing domestic reference values. Data on body weight, food consumption; urinalysis, hematological, and blood biochemical parameters; and organ weights were collected from 11 toxicity studies in 220 Crl:CD (SD) rats (110 males and 110 females). The studies had been performed at a single testing facility over the last 5 years and involved animals sourced from a single breeder. The findings were collated as means, standard deviations, percentages, and ranges. Urine volume, uterus weight, eosinophil, and basophil counts, and triglyceride, total bilirubin, and gamma-glutamyl transpeptidase levels showed standard deviations of 30% or more. These historical control data would help to interpret the effects of test substances in routine toxicity and efficacy studies.
Animals
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Basophils
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Bilirubin
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Body Weight
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Eosinophils
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gamma-Glutamyltransferase
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Humans
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Male
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Organ Size
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Rats
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Reference Values
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Sprains and Strains
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Toxicology
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Urinalysis
;
Uterus
10.13-week subchronic toxicity study of a novel ginsenoside composition from ginseng leaves in rats.
Won Ho SHIN ; Yu RI ; Seon Gil DO ; Young Chul LEE ; Sang Joon PARK
Laboratory Animal Research 2014;30(3):112-122
UG0712 is a new ginsenoside extract processed from ginseng leaves. A subchronic toxicity study of UG0712 was conducted in male and female SD rats. Rats were treated with UG0712 at doses of 100, 400 and 1,600 mg/kg/day for 13 weeks, and observed followed by 4-week recovery period at a highest dose. No-treatment-related effects were observed regarding the mortality, ophthalmic examination, urinalysis and histopathology. Although the changes in clinical sign, body weight, organ weight, hematology, and serum biochemistry were observed, they were temporal and pharmacological effects. Based on the present experiment conditions, the no observed adverse effect level was considered to be more than 1,600 mg/kg/day in both sexes of rats.
Animals
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Biochemistry
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Body Weight
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Female
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Hematology
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Humans
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Male
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Mortality
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No-Observed-Adverse-Effect Level
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Organ Size
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Panax*
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Rats*
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Urinalysis