• Title/Summary/Keyword: Acute toxicity

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The effects of immune activating herbs on the anti-tumor activity (한약(韓藥)의 면역조절(免疫調節) 작용(作用)을 통(通)한 종양치료(腫瘍治療)에 대(對)한 연구(硏究))

  • Lee, Jung-Soo;Lee, Yeon-Weol;Cho, Jung-Hyo;Son, Chang-Kyu;Yoo, Hwa-Seung;Cho, Chong-Kwan
    • THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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    • v.9 no.1
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    • pp.65-73
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    • 2003
  • The researches for tumor and the developments for new anti-tumor medicine are being continuously developed in the oriental as well as the west. The principles therapy of anti-tumor activity was based on knowledge of the method of support the healthy energy and strengthen the body resistance, promote blood circulation to remove blood stasis, clear away heat and toxic materials, dissipate phlegm and disperse the accumulation of evils. But the major clinical features of tumor was to be considered in developing a treatment plan include (1) distinguish between clinical and pathologic staging - acute and chronic, (2) classification of pathologic pattern, and (3) distinction of body situation : for examples asthenia - sthenia etc. It was most important to distinguish between supporting the healthy and eliminating the evil factors and to treat differently at the root and the branch cause of a neoplasm. In clinical study and experimental study, the effects of oriental medicine could be summarized as three that were decreasing toxicity of chemo-therapy, directly suppressing and killing cancerous cell and increasing chemo-effect through preventing metastasis. Improving organic immunity with oriental medicine could be summarized as five that were promoting phagocytosis of macrophage, inducing interferon, promoting formation of immnoglobulin, increasing number of T-cell and promoting transformation of lymphocyte. It is suggested that effective use of immune activating herbs inhibited metastasis and decreased recurrence and then we were able to expect increasing survival rate and improving clinical symptoms and quality of life(QOL) of tumor patients.

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Protective Effect of Joo-Juk on Acetaminophen-induced Liver Damage in Mouse Model (Acetaminophen 유도 간 손상에 대한 주적(酒敵)의 보호 효과)

  • Kim, Sung-Zoo;Kang, Hyung-Sub;Shin, Jae-Suk;Xie, Guang-Hua;Huh, Jin;Jang, Seon-Il
    • Herbal Formula Science
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    • v.17 no.2
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    • pp.123-132
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    • 2009
  • Acetaminophen (AP) is widely used as an over-the-counter analgesic and antipyretic drug. AP-induced hepatotoxicity is a common consequence of AP overdose and may lead to acute liver failure. In this study, we investigated the liver damage in mice using single dose (300 mg/kg) of AP and the possible protective effects of administration (50-200 mg/kg body weight) of Joo-Juk on acetaminophen-induced liver damage in mice. The alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activities were determined in the plasma of mice. The effect of Joo-Juk on lipid peroxidation product thiobarbituric reacting substances (TBARS) and some antioxidant enzymes superoxide dismutase (SOD), catalase, d-aminolevulinate dehydratase ($\sigma$-ALA-D) activities, and gluthathione peroxidase (GPx), were also evaluated in the mouse liver homogenate. AP caused liver damage as evident by statistically significant increased in plasma activities of AST and ALT. There were statistically significant losses in the activities of SOD, catalase, $\sigma$-ALA-D, and GPx and an increase in TBARS in the liver of AP-treated group compared with the control group. However, Joo-Juk was able to counteract these effects. These results suggest that Joo-juk can act as hepato-protectant against AP toxicity and is a good candidate for further evaluation as an effective chemotherapeutic agent.

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The Effects of Shihosogan-san on Alcohol-induced Muscle Atrophy in Rats (흰쥐의 만성 알콜성 근위축에 시호소간산(柴胡疎肝散)이 미치는 효과)

  • Kim, Bum Hoi
    • Herbal Formula Science
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    • v.24 no.4
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    • pp.311-321
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    • 2016
  • Chronic or acute alcohol abuse often leads to liver injury associated with alcoholic hepatitis, liver fibrosis, cirrhosis, and liver cancer. In addition to the liver, alcohol abuse also induces a variety of other tissue injuries including pancreatitis, cardiomyopathy, neurotoxicity and muscle loss. Chronic skeletal muscle myopathy, independent of peripheral neuropathy, is well recognised in alcoholic patients. Several mechanisms may be involved in the pathogenesis of alcoholic myopathy. Ethanol is a potent inhibitor of muscle protein synthesis. Gastrocnemius and plantaris muscles are Type II fiber-predominant and usually considered representative of the musculature as a whole. Whereas, soleus muscle is Type I fiber predominant. Shihosogan-san is a traditional Korean medicine that is widely employed to treat indigestion and liver diseases. Muscle diseases are often related to liver diseases and conditions. We therefore tested the hypothesis that treatment with Shihosogan-san could ameliorate the ethanol-induced changes in muscle protein synthesis. Young male Sprague-Dawley rats were orally given 25% ethanol (5ml/kg, body weight) daily with Ethanol for 28 days. Normal group was similarly administrated with saline. In Shihosogan-san treated group, rats were orally administrated Shihosogan-san extract, and rats of EtOH group were given with the vehicle only. After 4 week, the morphology of gastrocnemius and plantaris muscles were assessed by hematoxylin and eosin staining. For comparative purposes, liver function was also investigated. The muscles from rats of EtOH group displayed a significant reduction in average cross section area compared to Normal group. Shihosogan-san treated group had increased fiber compared to the EtOH group. Moreover, Shihosogan-san treated group compared with EtOH group showed significantly decreased pro-apoptotic BAX expression and increased anti-apoptotic Bcl-2 expression. In conclusion, Shihosogan-san extract showed ameliorating effects on chronic alcohol toxicity in skeletal muscle.

Inhibitory Effect of Salvia miltiorrhiza Extract on Growth of Some Cancer Cells (단삼(Salvia Miltiorrhiza) 추출물의 암세포 증식 억제 효과에 관한 연구)

  • 정국찬;이지영;김동청;서성옥;황우익
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.29 no.4
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    • pp.726-731
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    • 2000
  • This study was performed to evaluate the antitumor activities of water and ethanol (EtOH) extract of Salvia miltiorrhiza in vitro and in vivo. The proliferation of the human hepatoma (HepG2), rectum cancer (HRT-18) and colon cancer (HT-29) cells was inhibited by administration of extracts in a dose-dependent manner. Particularly, EtOH extract inhibited proliferation of the cells more effectively than water extract did. The morphology of cells induced by EtOH extract was characterized by reduction of cell size and deformatin. Oral administration of the EtOH extract (3 mg/head) to tumor-bearing mice inhibited the tumor (sarcoma-180) growth by 35% and prolonged their survival rate by 61%. The EtOH extract was shown to be nontoxic at 37.5% mg/head/day on the acute toxicity test. These studies suggest that the EtOH extract of Salvia miltiorrhiza may have antitumor activity in vitro and in vivo.

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Studies on the Yellow Pigment Produced by Monascus sp. CS-2 (Part 3) Safety Test of Yellow Pigment (Monascus sp. CS-2가 생산하는 황색색소에 관한 연구 (제3보) 황색색소의 안전성 시험)

  • Kim, Hyun-Soo;Jang, Wook;Son, Chung-Hong;Bae, Jong-Chan;Yoo, Ju-Hyun
    • Microbiology and Biotechnology Letters
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    • v.9 no.3
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    • pp.117-121
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    • 1981
  • Safety of yellow pigment produced by Monascus sp. CS-2 was evaluated. Acute oral toxicity, pyrogen test, and histamine test, as well as antimicrobial activity were determined. The results obtained were; LD oral in mice was 132.5 mg/20 g, pyrogen test in rabbit was 5 mg/kg, and histamine test in cat was 10 mg/kg. Also the pigment was particularly sensitive to Bacillus subtilis (ATCC 6633), Sarcina lutea (ATCC 9341) and Staphylococcus aureus (ATCC 6538 P), whereas not sensitive to Pseudomonas pyosyanea (ACTC 10490), Bacillus var. mycoides (ATCC 11778), Bordetella bronchiseptica (ATCC 4617) and Staphylococcus epidermidis(ATCC 12228).

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Assessing the Systemic Toxicity in Rabbits after Sub Acute Exposure to Ocular Irritant Chemicals

  • Reshma, Cherian Sebastian;Sruthi, Sudhakaran;Syama, Santhakumar;Gayathri, Vishwanath;Mohanan, Parayanthala Valappil
    • Toxicological Research
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    • v.31 no.1
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    • pp.49-59
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    • 2015
  • Eye is a highly vascularised organ. There are chances that a foreign substance can enter the systemic circulation through the eye and cause oxidative stress and evoke immune response. Here the eyes of rabbits were exposed, for a period of 7 days, to 5 known ocular irritants: Cetyl pyridinium chloride (CPC), sodium salicylate (SS), imidazole (IMI), acetaminophen (ACT) and nicotinamide (NIC). The eyes were scored according to the draize scoring. Blood collected from the treated rabbit were analyzed for haematological and biochemical parameters. After sacrifice, histological analysis of the eye and analysis of pro-inflammatory biomarkers ($IL-1{\alpha}$, $IL-1{\beta}$, IL-8 and $TNF-{\alpha}$) in the cornea using ELISA was carried out. Spleen was collected and the proliferation capacities of spleenocytes were analyzed. Liver and brain were collected and assessed for oxidative stress. The eye irritation potential of the chemicals was evident from the redness and swelling of the conjunctiva and cornea. Histopathological analysis and ELISA assay showed signs of inflammation in the eye. However, the haematological and biochemical parameters showed no change. Spleenocyte proliferations showed only slight alterations which were not significant. Also oxidative stress in the brain and liver were negligible. In conclusion, chemicals which cause ocular irritation and inflammation did not show any systemic side-effects in the present scenario.

Studies on the Preparation of Processed Aconiti Tubers (무독부자(無毒附子)의 제조에 관한 연구)

  • Park, Shin-Young;Chung, Bo-Sup;Lee, Hyeong-Kyu;Lee, Hyun-Sun;Ryu, Jong-Hyeon
    • Korean Journal of Pharmacognosy
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    • v.20 no.1
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    • pp.25-31
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    • 1989
  • In order to establish the standard method for the preparation of processed Aconiti Tuber, Aconiti Tubers were processed under various conditions and the amount and the composition of alkaloids were determined by HPLC. The ratio of sum of benzoylhypaconine and benzoylmesaconine over the sum of acinitine, mesaconitine, benzoylmesaconine and benzoylhypaconine was used as a detoxification index ((BM+BH)${\times}$100/MA+AC+BM+BH). The adequate value of index was obtained from Japanese 'ka-gong bu-ja' which has been used in Japan. The processing procedure was largely devided into two categories. First is heat treating at $120^{\circ}$ and 1. 2 lbs for 60 min. Second is treatment with various kinds of alkaline solutions followed by heat treatment at $120^{\circ}$ and 1. 2 lbs for 60 min. Among the source of processed Aconiti Tubers, dried bu-ja and yom bu-ja, dried bu-ja was more adequate than yom bu-ja because yom bu-ja has the lower value of index than dried bu-ja and lost active components through the desalting periods. Dried bu-ja whish was treated with alkaline solutions followed by heat treatment has the detoxification index, 50% and dried bu-ja which was treated only with hear has 71. 8%. Compared to the value of index of Japanese 'ka-gong bu-ja', 72%, the dried bu-ja treated with heat at $120^{\circ}$ and 1, 2 lbs for 60min was the most adequate. The $LD_{50}$ value of the processed bu-ja was higher than 15 g crude drugs/kg, p.o. in mice.

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Effects of Dried Gentiana scabra Rhizomes and Roots on the Intestinal Transit Rate of Mice with Experimental Gastrointestinal Motility Dysfunctions (용담 열수 추출물이 위장관 운동 기능 저해 상황에서 위장관 이송률에 미치는 영향)

  • Lee, Hyun-Tai
    • Journal of Life Science
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    • v.29 no.12
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    • pp.1345-1350
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    • 2019
  • Our recent study has revealed that in vivo intestinal transit rate (ITR) in normal mice was significantly increased by the administration of an aqueous extract of dried Gentiana scabra rhizomes and roots (GS-W) in a dose-dependent manner. Following on from our previous study, the effect of GS-W on ITR was measured in mice with experimentally induced gastrointestinal motility dysfunctions (GMDs) in the present study. GS-W showed no significant acute toxicity even at an oral dose of 5 g/kg to mice. ITR was significantly retarded in the GMD mice compared with that in normal mice, and this retardation was significantly recovered by the oral administration of GS-W in a dose-dependent manner. Furthermore, the ITR value of GS-W at a dose of 1 g/kg appeared to be higher than that of cisapride, which was predominantly prescribed for human patients with various GMDs in the late 1900s but was withdrawn from the market in 2000 due to its fatal side effects. The current results suggest that GS-W is a potential substitute for cisapride to prevent or alleviate human GMDs.

Effects of Arsenic Compounds $(AS_2O_3\;and\;AS_4O_6)$ on the Induction of Apoptotic Cell Death in A549 Human Non-small Cell Lung Cancer Cells (비소화합물에 의한 A549 폐암세포의 증식억제에 관한 연구)

  • Choi, Yung-Hyun;Choi, Woo-Young;Choi, Byung-Tae;Lee, Yong-Tae;Lee, Won-Ho
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.19 no.4
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    • pp.1050-1054
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    • 2005
  • Recently, arsenic compounds were considered as novel agents for treatment of acute promyelocytic leukemia and malignant tumors. However, it showed severe toxicity effect on normal tissue at the same time. In this study, to investigate the possible molecular mechanism (s) of arsenic compounds as candidate of anti-cancer drugs, we compared the abilities of two arsenic compounds, tetraarsenic oxide $(AS_4O_6)$ and arsenic trioxide (diarsenic oxide, $As_2O_3$), to induce cell growth inhibition as well as apoptosis induction in A549 human non-small cell lung cancer cells. Both $As_4O_6\;and\;As_2O_3$ treatment declined the cell growth and viability of A549 cells in a concentration-dependent manner, which was associated with induction of G1 arrest of the cell cycle and apoptotic cell death. However, $As_4O_6$ induced growth inhibition and apoptosis in A549 cells at much lower concentrations than $As_2O_3.\;As_4O_6$ down-regulated the levels of anti-apoptotic Bcl-2 protein, however, the levels of Bax, a pro-apoptotic protein, were up-regulated in a dose-dependent manner. In conclusion, $As_4O_6$ might be a new arsenic compound which may induce apoptosis in A549 cells by modulation the Bcl-2 family and deserves further evaluation.

Toxicological Aspects of Carboxylesterases -A Sensitive Biomarker of Organophosphate Toxicity-

  • Satoh, Tetsuo;Suzuki, Satoshi;Hosokawa, Masakiyo
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1998.11a
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    • pp.108-113
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    • 1998
  • Egasyn is accessory protein of ${\beta}$-glucuronidase(${\beta}$-G) in the liver microsomes. Liver microsomal ${\beta}$-G is stabilized within the luminal site of the microsomal vesicles by complexation with egasyn which is one of carboxylesterase isozymes. We investigated the effects of organophosphorus compounds(OPs) such as insecticides on the dissociation of egasyn-${\beta}$-glucuronidase(EG) complex. The EG complex was easily dissociated by administration of OPs, i.e., Fenitrothion, EPN, Phenthionate, and bis-p-nitrophenyl phosphate(BNPP), and resulting ${\beta}$-G dissociated was released into blood, leading to the rapid and transient increase of plasma ${\beta}$-G level with a concomitant decrease of liver microsomal ${\beta}$-G level. In a case of phenthionate treatment, less increase in plasma ${\beta}$-G level was observed, as compared with those of other OPs. This may be explained by a fact that phenthionate was easily hydrolyzed by carboxylesterase. Similarly, carbamate insecticides such as Carbaryl caused rapid increase of plasma ${\beta}$-G level. In contrast, no significant increase of plasma ${\beta}$-G level was observed when pyrethroid insecticides were administered to rats. This is due to a fact that pyrethroids such as Phenthrin and Allethrin were easily hydrolyzed by A-esterase as well as carboxylesterase. On the other hand, addition of OPs to the incubation mixture containing liver microsomes caused the release of ${\beta}$-G from microsomes to the medium. From these in vivo and in vitro data, it is concluded that increase of the plasma ${\beta}$-G level after OPs administration is much more sensitive biomarker than cholinesterase inhibition to acute intoxication of OPs and carbamates.

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