• Toxicological Research
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• v.31 no.4
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• pp.403-414
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• 2015

Lithospermum erythrorhizon has long been used as a traditional oriental medicine. In this study, the acute and 28-day subacute oral dose toxicity studies of hexane extracts of the roots of L. erythrorhizon (LEH) were performed in Sprague-Dawley rats. In the acute toxicity study, LEH was administered once orally to 5 male and 5 female rats at dose levels of 500, 1,000, and 2,000 mg/kg. Mortality, clinical signs, and body weight changes were monitored for 14 days. Salivation, soft stool, soiled perineal region, compound-colored stool, chromaturia and a decrease in body weight were observed in the extract-treated groups, and no deaths occurred during the study. Therefore, the approximate lethal dose (ALD) of LEH in male and female rats was higher than 2,000 mg/kg. In the subacute toxicity study, LEH was administered orally to male and female rats for 28 days at dose levels of 25, 100, and 400 mg/kg/day. There was no LEH-related toxic effect in the body weight, food consumption, ophthalmology, hematology, clinical chemistry and organ weights. Compound-colored (black) stool, chromaturia and increased protein, ketone bodies, bilirubin and occult blood in urine were observed in the male and female rats treated with the test substance. In addition, the necropsy revealed dark red discoloration of the kidneys, and the histopathological examination showed presence of red brown pigment or increased hyaline droplets in the renal tubules of the renal cortex. However, there were no test substance-related toxic effects in the hematology and clinical chemistry, and no morphological changes were observed in the histopathological examination of the kidneys. Therefore, it was determined that there was no significant toxicity because the changes observed were caused by the intrinsic color of the test substance. These results suggest that the no-observed-adverse-effect Level (NOAEL) of LEH is greater than 400 mg/kg/day in both sexes.

• Journal of Life Science
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• v.15 no.3 s.70
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• pp.387-396
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• 2005

The aims of the study were to establish a short-term screening test for detecting testicular toxicity of chemicals in rats and to determine whether a 2-week administration period is sufficient to detect testicular toxicity of 2-bromopropane (2-BP) as an example. Male Sprague-Dawley rats were subcutaneously administered with 1000 mg/kg/day of 2-BP or its vehicle for 2 weeks. Ten male rats each were sacrificed on days 3, 7 and 14 after the initiation of treatment. Parameters of testicular toxicity included genital organ weights, testicular sperm head counts, epididymal sperm counts, motility and morphology, and qualitative and quantitative histopathologic examinations. The early histopathological changes observed on day 3 of treatment included degeneration of spermatogonia and spermatocytes, multinuclear giant cells, mature spermatid retention, vacuolization of Sertoli cells, and decreased number of spermatogonia in stages II and V. On day 7 of treatment, atrophy of seminiferous tubules, exfoliation of germ cells, degeneration of spermatogonia and spermatocytes, multinuclear giant cells, mature spermatid retention, vacuolization of Sertoli cells, decreased number of spermatogonia in stages II and V, and decreased number of spermatocytes in stages VII and XII. On day 14 after treatment, a significant decrease in the weights of testes and seminal vesicles was found. Atrophy of seminiferous tubules, exfoliation of germ cells, degeneration of spermatogonia and spermatocytes, mature spermatid retention, vacuolization of Sertoli cells, decreased number of spermatogonia in stages II and V, and decreased number of spermatocytes in all spermatogenic stages were also observed. In addition, a slight non-significant decrease in testicular sperm head counts, daily sperm production rate and epididymal sperm counts was found. The results showed that 2 weeks of treatment is sufficient to detect the adverse effects of 2-BP on male reproductive organs. It is considered that the short-term testicular toxicity study established in this study can be a useful tool for screening the testicular toxic potential of new drug candidates in rats.

• Journal of Nutrition and Health
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• v.34 no.8
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• pp.850-857
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• 2001

The study was designed to observe whether the conjugated linoleic acid supplemented to diet could reduce plasma levels of glucose and lipids which were increased in 27-weeks old Otsuka Long Evans Tokushima Fatty(OLETF) rats. Twenty male OLETF rats of 7 weeks old were fed an experimental diet containing 4.5%(w/w) total fat including 1% CLA and six of twenty rats were sacrified at 6 weeks feeding. The rest of OLETF rats was divided into 2 groups, one group was continuously fed for 14 weeks more the same experimental diet containing 1% CLA and the other group was fed control diet which eliminated CLA. CLA did not significantly reduce food intake and body weight gain in OLETF obese rats. Plasma triglyceride and total cholesterol level were significantly increased at older age of OLETF obese rats, but CLA could significantly reduce plasma cholesterol and triglyceride increased in obese rats. However, CLA was not strong enough to reduce the increased plasma glucose level and hepatic lipogenic enzyme acitivies. CLA was mostly deposited in epididymal fat pad and could be incorporated into hepatic microsomal membrane and did interfere the conversion of C18 : 0 into C18 : 1 in liver. In conclusion, CLA could have anti-atherogenic effect by reducing plasma cholesterol and triglyceride which was increased in genetically obese rats, but CLA(1%) was not good source of dietary fatty acid to reduce body fatness and plasma glucose which was increased by obese gene in older rats.

• Journal of Nutrition and Health
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• v.27 no.9
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• pp.949-956
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• 1994

The effect of zinc deficiency on certain immunological parameters was investigated using intragastric tube feeding to obviate decreased food intake and altered eating pattern. Male, Fischer 344 rats were bilaterally adrenalectomized(ADX) or sham operated(SHAM). ADX rats received 0.9% NaCl in their drinking water and corticosterone injections at the dose of 1mg/kg of body weight three times per day. After recovery, one half of ADX and SHAM animals were tube-fed a purified, liquid diet containing either two ppm of zinc(zinc-deficient, force-fed ; ZDF) or 50ppm(zinc-replete, force-fed ; ZRF) for 19 days. They received identical amounts of diet based on the intake of ad libitum-fed, zinc-replete rats. Although they received identical amounts of food, ZDF rats grew at a slower rate compared to ZRF rats in both SHAM and ADX rats. Regardless of surgery, force-feeding rats the zinc-deficient diet resulted in a substantial decrease in serum zinc levels. The weights of the thymus, lymph node, and spleen were lower in SHAM-ZRF rats compared to SHAM-ARF rats. Marginal zinc deficiency caused lymphopenia in SHAM animals. However, these differences in lymphoid tissues and cells between SHAM-ZDF and SHAM-ZRF rats disappeared in ADX rats. These results indicate that the impaired growth of lymphoid tissues observed in zinc-deficient, sham-operated animals can be attributed to elevated serum corticosterone levels under the conditions of our experiments.

• Korean Journal of Rural Living Science
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• v.5 no.2
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• pp.125-134
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• 1994

This study was performed to observe the effects of dietary fat levels and sources on lipids contents and cellularities of liver, brain, and adipose tissue of early weaned rats. Male Sprague-Dawley rats were prematurely weaned from postnatal 17th day with the experimental diets differ in fat levels : low(5%), medium(10%), high(20%) and fat sources : butter, soybean oil, butter＋ soybean oil. On the postnatal 29th day, contents of total lipid, triglyceride, cholesterol and phospholipid of serum, liver, brain and adipose tissue were determined, and DNA was determined to assess the cell growth. Rats early weaned fed high fat diet showed lower total lipid and triglyceride levels in serum and liver than those fed medium or low fat diet Rats early weaned fed high fat diet had adipocytes of fewer number, but larger size than those of rats fed low or medium fat diets. Rats early weaned fed soybean oil diet had more adipocytes thu those fed butter diet. Rats normally weaned to commercial chow diet showed lower total lipid, triglyceride, and cholesterol levels in serum and liver, had fewer adipocytes than all early weaned rats except for rats fed high fat-butter diet. These results suggest that high fat-butter diet is ideal weaning diet at early weaning.

• Journal of Food Hygiene and Safety
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• v.9 no.2
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• pp.57-66
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• 1994

The benefits of milk on the rats supplemented with cholesterol and vitamin D2 in diet was investigated. A total of 150 male rats of Sprague-Dawley strain, 5 weeks of age, were divided into 6 groups with the diet. Cholesterol control group was fed the diet containing 1.0% choleterol and 50,000 IU/100 g of vitamin D2 for 24 months, and M0.5, M1, M2 and M5 of milk groups were fed the diet containing cholesterol, vitamin D2 and 0.5, 1, 2 and 5 of reference daily intakes of whole milk, respectively. No remarkable differences of growth, diet intake, and food effciency ratio among groups were observed though rats in cholesterol control group showed abrupt decrease of diet intake and body weight showed slightly higher relative organ weights than did the rats in control group. The rats in cholesterol control group showed the highest serum total cholesterol level. The rats in milk groups showed lower total cholesterol level and higher high density lipoprotein (HDL)-cholesterol fraction than did the rats in cholesterol control group though no tendency was observed among milk groups. In milk groups, aorta, heart, kidney and liver of rats showed milder calcification and necrosis or fat degeneration compared with those in cholesterol control group. The above results suggest that whole milk could have beneficial effect on the cholesterol-and -vitamin D2-induced atherosclerosis in rats.

• Journal of Microbiology and Biotechnology
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• v.29 no.4
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• pp.658-664
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• 2019

Immunocontraception has been suggested as an optimal alternative to surgical contraception in animal species. Many immunocontraceptive vaccines have been designed to artificially produce antibodies against gonadotropin-releasing hormone-I (GnRH-I) which remove GnRH-I from the vaccinated animals. A deficiency of GnRH-I thereafter leads to a lack of gonadotropins, resulting in immunocontraception. In this study, we initially developed three immunocontraceptive vaccines composed of GnRH-I, GnRH-II, and a GnRH-I and -II (GnRH-I+II) complex, conjugated to the external domain of Salmonella Typhimurium flagellin. As the GnRH-I+II vaccine induced significantly (p < 0.01) higher levels of anti-GnRH-I antibodies than the other two vaccines, we further evaluated its immunocontraceptive effects in male rats. Mean testis weight in rats (n = 6) inoculated twice with the GnRH-I+II vaccine at 2-week intervals was significantly (p < 0.01) lower than in negative control rats at 10 weeks of age. Among the six vaccinated rats, two were non-responders whose testes were not significantly reduced when compared to those of negative control rats. Significantly smaller testis weight (p < 0.001), higher anti-GnRH-I antibody levels (p < 0.001), and lower testosterone levels (p < 0.001) were seen in the remaining four responders compared to the negative control rats at the end of the experiments. Furthermore, seminiferous tubule atrophy and spermatogenesis arrest were found in the testis tissues of responders. Therefore, the newly developed GnRH-I+II vaccine efficiently induced immunocontraception in male rats. This vaccine can potentially also be applied for birth control in other animal species.

• Asian-Australasian Journal of Animal Sciences
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• v.32 no.8
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• pp.1145-1152
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• 2019

Objective: Mulberry (Morus alba L.) is a cultivated shrub grown widely in the sub-tropical and tropical areas. It has been shown that mulberry leaf contains high levels of protein while having polyphenols as phytonutrients. Therefore, it is important to conduct an experiment to assess potential toxic level from mulberry on behavior, blood hematological and coagulation parameter using Sprague-Dawley (SD) rats. Methods: Both male and female SD rats were given an intragastric administration of respective treatments of mulberry leaf intakes (control, low and high levels). Parameters of feed intake, hematological and coagulation of blood parameters, as well as liveweight changes were taken during the 7 d of adaptation, 28 d of treatment exposure, and 14 d of recovery periods, respectively. All treatment data were statistically analyzed using analysis of variance of SPSS17.0 for Windows Statistical Software following the Randomized complete block design with sex as a block. Results: Most of the parameters of the physical symptoms of the SD rats, were not significantly different (p>0.05) when compared with that of the control group. Those which remain unchanged in each dose group were, body weight (BW) gain, feed intake, the hematology and coagulation indexes. Although, there were a few individual indicators that were abnormal, but the overall physiological appearance of the rats were normal. Conclusion: Results under this experiment revealed that most hematological and coagulation parameters of the SD rats in both male and female were normal, although the weight gain of female rats in high-dose group was significantly reduced than those of the male rats. Under this study, the use of mulberry leaf up to 2 g/kg BW did not result in abnormal phenomenon in the SD rats. These findings would offer useful information for further in vivo feeding trials in animals to extensively use of mulberry leaf to improve animal production, particularly in P.R. China.

• Journal of Environmental Health Sciences
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• v.33 no.2 s.95
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• pp.132-136
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• 2007

The present study was carried out to examine the bone healing effect of a magnet as the feasibility test for clinical application. The surgical technique of tibia puncture was performed with male Sprague Dawley rats for investigating radiological and histological findings. The treated group was attached the magnet, and control group was attached the placebo magnet for 4, 6, and 8 weeks respectively. The rats were taken a radiograph for examining radiological findings on 2-weekly interval for 8 weeks. Also, the rats were partly euthanized for investigating histological findings on 2-weekly interval from 4 week to 8 week. In the magnet treated rats, the healing process of bone trauma was positively stimulated to compare with control rats.

• Biomolecules & Therapeutics
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• v.3 no.1
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• pp.12-20
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• 1995

Clofibrate, a peroxisome proliferator, is hepatocarcinogenic in rats in a dose-dependent manner. A total of 70 male and female F344 rats, 5-week-old, were divided into three groups. Rats were fed clofibrate at 0, 0.25, or 0.5% in diet for 30 days. All rats were anesthetized with $CO_2$, blood samples were taken by cardiac puncture for hematology and clinical chemistry, and the rats were killed by exsanguination. Livers, kidenys, pancreas, adrenal glands, spleen, heart, lungs, thyroid gland, reproductive organs, and digestive organs were removed, weighed, later processed, and embedded with paraplast for histological examination. The relative liver and kidney weights with respect to final body weight in the clofibrate-treated group were significantly increased compared with those of control group at all dose levels (p<0.01). It has been suggested that clofibrate may influence on hepatotoxicity by increases in peroxisomal proliferation.