• Journal of Acupuncture Research
• /
• 제38권1호
• /
• pp.47-59
• /
• 2021

Background: This study aimed to assess the toxicity of Aconitum sinomontanum Nakai (ASN) pharmacopuncture. Methods: To investigate the toxicity of ASN pharmacopuncture, single and 4-week repeated dose toxicity experiments were conducted on BALB/c mice. In the single-dose toxicity experiment, mice were assigned 1 of 4 groups (5 males, 5 females per group). Then, 31.25, 62.5, and 125 mg/kg of ASN pharmacopuncture were administered to the mice in the experimental groups at acupoint ST36, while 0.2 mL of normal saline was administered to the control group at ST36. After a 4-week repeated dose regimen, the mice were assigned into 4 groups (5 males, 5 females per group). Then, 15.625, 31.25, and 62.5 mg/kg of ASN pharmacopuncture at ST36 were administered to the mice in the experimental groups, while 0.2 mL of normal saline was administered to the control group at ST36. Mortality, morbidity, general body and organ weight changes (after 4 weeks repeated dose), serum hematological and biochemical values, and histopathological changes in the liver and kidney were observed. Results: In both single and 4-week repeated dose toxicity experiments, no deaths or symptoms occurred in any of the groups. There were no significant differences between groups in terms of body and organ weights, serum hematological and biochemical values, and specific organ histopathological changes. Conclusion: ASN pharmacopuncture injection did not demonstrate significant toxicity in BALB/c mice compared with the control group, with a no-observed-adverse-effect level for a single dose of >125 mg/kg, and for 4 weeks repeated dose it was more than 62.5 mg/kg/day.

• Journal of Ginseng Research
• /
• 제14권2호
• /
• pp.200-206
• /
• 1990

The effects of ginseng saponins, SRbl and G-Rc on the rat liver LDH A-gene transcriptional activity was investigated during prereplicative phase of rat liver after partial hepatectomy. Changes in LDH A-mRNA levels in regenerating rat liver after intraperitoneal administrations of G-Rbl or 'G-Rc were tested by slot blot hybridization methods. The results showed that G-Rbl (1 mg/100g B.W) and G-Rc (1 mg/100g B.W) caused marked increases of LDH A-mRNA contents by respectively 1.9- and 1.5-fold in rat liver at 5-hours after partial hepatectomy Dose dependent elect of G-Rbl and G-Rc (1-25 mg/ 100g B.W) on the LDH A-mRNA levels on regenerating rat liver were also analyzed. The maximal increases of liver LDH A-mRNA levels were observed with the doses of 1 mg for G-Rbl and 5 mg for G-Rc. However, when the administration doses of G-Rbl and G-Rc were increased to 20 mg, G-Rbl caused a marked decrease of LDH A-mRNA level to 61% of those in sham-operated rat liver. In contrast, G-Rc slightly decreased the liver LDH A-mRNA contents by 30% as compared to those of the maximum value but still maintained 22% higher LDH A-mRNA levels then those of sham-operated rate liver. On the basis of these experimental results, we conclude that ginseng saponin, G-Rbl and G-Rc have stimulatory effect at the lower concentration (1 mg/ 100g B.W) and inhibitory effect at the higher concentration (20 mg/ 100g B.W) on the LDH A-gene transcription during regeneration of rat liver. Additionally we also investigated the stimulatory effects of ginsenosides on the protein and DNA sinthetic activities in hepatocyte primary cell cultures isolated from regenerating rat liver. Both of G-Rc and -Re increased the synthetic rates of hepatocytes proteins and DNA at the administration doses of 50 us and 100 $\mu\textrm{g}$/3 ml/dish respectively representing 1.3-1.6 fold increases. From these results we postulate that G-Rc and -Re may have a mitogen ehincer activity for the hepatocyte proliferation during rat liver regeneration period.

• 동의생리병리학회지
• /
• 제18권5호
• /
• pp.1331-1336
• /
• 2004

The present study evaluated the beneficial effect of new diabetic formula(NDF) in diabetic rats. Adult Sprague-Dawley rats weighing 250-300 g were used. Diabetes mellitus was induced by intramuscular injections of streptozotocin(STZ, 50㎎/㎏). The extracts of NDF were orally administered at low or high dose two times a day to fasted diabetic rats for 3 weeks. Adminstration of NDF alliviated a significant reduction in weight gain in rats with STZ-induced diabetes. Following acute and repeated treatment, low dose of NDF suppressed the blood glucose concentrations of fasted diabetic rats. Repeated adminstration of NDF for 21 days improved liver and kidney functions in diabetic rats, as indicated by decline of serum alanine aminotransferase(AL T), alkaline phosphatase(ALP), blood urea nitrogen(BUN), creatinine level and kidney weights. The present study showed that NDF exerted antihyperglycemic effects and alliviated liver and renal damages caused by streptozotocin-induced diabetes.

• 생약학회지
• /
• 제14권3호
• /
• pp.95-101
• /
• 1983

Aucubin, an iridoid glucoside which was previously reported to exhibit liver-protective activities against $CCl_4$ and ${\alpha}-amanitin$ induced liver damages, was subject to toxicological studies. To measure the lethal dose, the doses of 100mg/kg, 300mg/kg, 600mg/kg and 900mg/kg were administered intraperitoneally to experimental mice. No death was observed 24 hrs later, but serum GOT and alkaline phosphatase activities were deceased slightly at the doses of 300mg to 900mg/kg, and the triglyceride contents were slightly increased. To investigate acute toxicity of aucubin itself, multiple dosages(20 mg/kg, 40 mg/kg and 80 mg/kg for four times a week) were injected intraperitoneally into mice, then serum enzymes activities and chemistries were assayed; no significant change of the enzyme activities of alkaline phosphatase, GPT, GOT in the test groups were observed in comparison with those of the control group, and the contents of triglyceride, glucose, urea nitrogen and total proteins in the test group serums appeared to be almost same levels as those of the control group were. Histological examiation on liver biopsy samples indicated no gross changes between the control group and the test group were noted. Therefore, aucubin appears to be apparently low toxic substance and its minimum lethal dose in mouse seems to be more than 0.9 g.

• 생약학회지
• /
• 제29권4호
• /
• pp.300-311
• /
• 1998

This study was attempted to investigate the effects of "Angelicae gigantis Radix extract" (AG.EX.) on the activities of GOT and GPT, the contents of total lipid, triglyceride, total cholesterol, phospholipid and ${\beta}-lipoprotein$ in serum, and the weight change ratio of body, liver and spleen in the experimentally induced hyperlipemic rats by administering the extract of 300 and 500 mg/kg p.o.. Significant test was performed by comparision with the biochemical values between control group and experimentally hyperlipemic rats. In the activities of s-GOT and s-GPT inhibition effects were significantly appeared in all dose of AG.EX. (especially more excellent in ethanol extract) and Angelicae acutilobae Radix extract (AA.EX.) as compared with the control group. The content of total lipid was remarkably decreased in all sample group when compared with the control group, and AA.EX. showed more excellent decreasing effect than AG.EX. The contents of triglyceride and total cholesterol were significantly lowered in all sample group, and more significantly decreased in water extract of AG.EX. and ethanol extract of AA.EX. The content of phospholipid was significantly decreased in all sample group and AG.EX. was more significantly decreased than AA.EX. The increasing rate of body weight in all sample groups except AA.EX. 500 mg/kg was increased more than control group and more significantly remarkable in dose of 300 mg/kg than 500 mg/kg. The increasing rate of liver weight in all sample groups was increased more than control group, and AG.EX. was more increased than AA.EX.

• Toxicological Research
• /
• 제22권2호
• /
• pp.87-93
• /
• 2006

The KFDA (Korea Food & Drug Administration) has performed a collaborative toxico-genomics project since 2003. Its aim is to construct a toxicologenomic database of 12 hepatotoxic compounds from mice livers. Phenylbutazone which is non-steroidal anti-inflammatory drug was assigned. It was administered at low (0.0238 mg/kg) and at high (0.238 mg/kg) dose (5 mice per group) orally to the postnatal 6 weeks ICR mice, then the serum and liver were collected at the indicated time (6, 24 and 72 h) after administration. Serum biochemical markers for liver toxicity were measured and histopathologic studies also were carried out. The gene expression profiling was carried out by using Applied Biosystems 1700 Full Genome Expression Mouse. The 2-way ANOVA was used to find genes that reflected phenylbutazone-induced acute toxicity or dose-dependant changes. By self-organization maps (SOM), we identified groups with unique gene expression patterns, some of them are supposed to be related to phenylbutazone induced toxicity, including lipid metabolism abnormality, oxidative stress, cell death and cytoskeleton destruction.

• 동의생리병리학회지
• /
• 제26권5호
• /
• pp.714-723
• /
• 2012

The object of this study was to evaluate the effect of Bupleuri Radix, aqueous extracts of the root part of Bupleurum falcatum on the 6-n-propyl-2-thiouracil (PTU)-induced rat hypothyroidism. Aqueous extracts of Bupleuri Radix (BR; yield = 11.73%) were administered, once day for 42 days from 2 weeks before start of PTU treatment as an oral dose of 300 and 150 mg/kg (body weight), and hypothyroidism was induced by daily subcutaneous treatment of PTU 10 mg/kg for 28 days. The changes on the body weight, thyroid gland weights, serum thyroid hormone - thyroid stimulating hormone (TSH), triiodothyronine ($T_3$) and thyroxine ($T_4$), serum lipid profiles - total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL) and triglyceride, liver antioxidant defense system - lipid peroxidation, $H_2O_2$, superoxide dismutase (SOD) and catalase (CAT), serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were observed with histopathology of thyroid glands. Results were compared with $LevoT_4$ 0.5 mg/kg treated rats. As results of PTU treatment, marked decreases of body weights, triglyceride contents, liver CAT activities and changes of serum thyroid hormone levels were observed with increases of serum AST, HDL contents, liver $H_2O_2$ and SOD activities and thyroid gland weight. In addition, marked hyperplasia of follicular cells with decreases of follicular colloid contents and sizes were demonstrated at histopathological inspections. However, these PTU induced hypothyroidism were dose-dependently inhibited by treatment of BR extracts, and BR extracts effectively regulated the hypothyroidism related changes on the antioxidant defense system. The results obtained in this study suggest that BR extracts have favorable effects on the thyroid hormone productions with beneficial effects on the hypothyroidism mediated by the modulatory effects on the antioxidant defense system.

• Nutrition Research and Practice
• /
• 제6권3호
• /
• pp.195-200
• /
• 2012

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.

• 동의생리병리학회지
• /
• 제24권4호
• /
• pp.630-637
• /
• 2010

The object of this study was to evaluate the effect of Lonicerae Flos, aqueous extracts of the dried flower bud part of Lonicera japonica on the 6-n-propyl-2-thiouracil (PTU)-induced rat hypothyroidism. Aqueous extracts of Lonicerae Flos (LF yield = 23.80%) were administered, once day for 42 days from 2 weeks before start of PTU treatment as an oral dose of 500 and 250 mg/kg (body weight), and hypothyroidism was induced by daily subcutaneous treatment of PTU 10 mg/kg for 28 days. The changes on the body weight, thyroid gland weights, serum thyroid hormone - thyroid stimulating hormone (TSH), tri-iodothyronine ($T_3$) and thyroxine ($T_4$), serum lipid profiles - total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL) and triglyceride were observed with liver antioxidant defense system - lipid peroxidation, $H_2O_2$, superoxide dismutase (SOD) and catalase (CAT) and serum asparte aminotransferase (AST) and alanine aminotransferase (ALT) analysis. Results were compared with Levothyroxine ($LT_4$) 0.5 mg/kg treated rats. As results of PTU treatment, marked decreases of body weights, serum thyroid hormone levels and triglyceride contents, liver $H_2O_2_3$ and SOD activities were observed with increases of serum AST and HDL contents, liver CAT activities, thyroid gland weight. However, these PTU induced hypothyroidism were dose-dependently inhibited by treatment of LF extracts, and LF extracts effectively regulated the hypothyroidism related changes on the antioxidant defense system. The results obtained in this study suggest that LF extracts have favorable effects on the thyroid hormone productions with beneficial effects on the hypothyroidism mediated by the modulatory effects on the antioxidant defense system.

• Toxicological Research
• /
• 제28권3호
• /
• pp.165-172
• /
• 2012

Raphanus sativus (Cruciferaceae), commonly known as radish is widely available throughout the world. From antiquity it has been used in folk medicine as a natural drug against many toxicants. The present study was designed to evaluate the hepatoprotective activity of radish (Raphanus sativus) enzyme extract (REE) in vitro and in vivo test. The $IC_{50}$ values of REE in human liver derived HepG2 cells was over 5,000 ${\mu}g/ml$ in tested maximum concentration. The effect of REE to protect tacrine-induced cytotoxicity in HepG2 cells was evaluated by MTT assay. REE showed their hepatoprotective activities on tacrine-induced cytotoxicity and the $EC_{50}$ value was 1,250 ${\mu}g/ml$. Silymarin, an antihepatotoxic agent used as a positive control exhibited 59.7% hepatoprotective activity at 100 ${\mu}g/ml$. Moreover, we tested the effect of REE on carbon tetrachloride ($CCl_4$)-induced liver toxicity in rats. REE at dose of 50 and 100 mg/kg and silymarin at dose of 50 mg/kg were orally administered to $CCl_4$-treated rats. The results showed that REE and silymarin significantly reduced the elevated levels of serum enzyme markers induced by $CCl_4$. The biochemical data were supported by evaluation with liver histopathology. These findings suggest that REE, can significantly diminish hepatic damage by toxic agent such as tacrine or $CCl_4$.