• Title/Summary/Keyword: Toxicity of NO

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Effects of Alcohol Intoxication and Moldy Rice Consumption on the Liver Lipid Content in Rat (Alcohol과 쌀 곰팡이의 Toxicity가 간(肝)의 지방(脂肪) 축적(蓄積)에 미치는 영향(影響))

  • Chung, C.E.;Kim, S.H.
    • Journal of Nutrition and Health
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    • v.6 no.4
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    • pp.37-53
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    • 1973
  • For the elucidation of the metabolic effects due to alcoholic drink and moldy rice intake author designed two experiments as follows. In the first experiment, sixty male and female rats, divided into six groups, 10 rats each in both sexes, were given 7.5% sucrose-30% alcohol solution (Jinro-Soju) and diets varied of fat content (2%, 7%, 30% of diet) and protein quality (casein, bean, anchovy) for 6 weeks. In the Second experiment, six groups of rats, 10 male rats each, were fed the diets containing zero, 5%, 10%, 25%, 50%, and 100% moldy rice contaminated Penicillium Islandicum and the experimental periods were 4 weeks and 6 weeks. The results of these studies due to the toxicity of alcohol consumption and moldy rice ingestion of the fatty liver production and the other effects are as follows. 1. Food intake of alcohol consumed groups decreased to 50%-70% of that of standard group. In the second study, there was no significant differences on food intake due to the different contents of moldy rice and experimental period. 2. On the view paint of body weight gain, the body weight of alcohol consumed groups gained much less than that of standard group, because food consumption was decreased due to alcohol ingestion. 3. In comparison of F.E.R. and P.E.R. between standard and experimental groups, there was no significant differences in this study. 4. As a matter of fact, there was no significance on the nitrogen balance in both studies. 5. From the result of hematology, R.B.C. counts, W.B.C. counts, hemoglobin, and hematocrit showed normal values in all groups including in this study. So we might conclude that the toxicity of alcohol and moldy rice do not effect significantly on blood picture. 6. The larger organs shrank on the range of 20%-70% of that against standard group in this study. The major reason for the shrinkage of organs might be account of decreased food consumption due to alcoholic drink. There was no great changes on the organ weight due to the ingestion of moldy rice. 7. The nitrogen content in various organs in both experiments was revealed at the normal level for the worst condition in terms of the least food intake. In other word, it was noteworthy that the concentration of nitrogen in various organs was kept at the normal ratio as standard groups under the circumstances of this study. 8. The lipid content in the liver of rats fed alcohol and diets containing either various lipid contents or protein quality did not increase. Hepatic lipids accumulation due to the dietary fat content was observed, but there wvas no significances among the compared groups. In the second experiment, the difference of hepatic lipid content between the moldy rice groups and standard group was not showed. In addition to the result of total lipid, hepatic free cholesterol, free fatty acid, and triglyceride did not change in both studies, we might conclude that the toxicity of alcohol and moldy rice could not effect on the hepatic lipid contents. 9. There was no significant differences on the serum glucose level between alcohol groups and standard group. In the second experiment, serum glucose level increase in 6th week compared with in 4th week, but there was no significant differences.

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Single & 14-Day Repeated Oral Toxicity Study and Genotoxicological Safety Estimate of Plantamajoside Isolated from Plantago asiatica (차전초(Plantago asiatica)로부터 분리된 Plantamajoside의 단회와 14일 반복투여 독성시험 및 유전독성학적 안전성 평가)

  • Park, Byung-Gyu;Lee, Hyun-Sun;Jung, Sung-Hoon;Koo, Yun-Chang;Hong, Chung-Qui;Lee, Sun-Joo;Lee, Kwang-Won
    • Toxicological Research
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    • v.23 no.1
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    • pp.79-86
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    • 2007
  • The isolated plantamajoside from Plantago asiatica that is often used as a marker compound in chemotaxonomic studies has various bioactivites such as the inhibitions of cyclic AMP phosphodi-esterase and 5-lipoxygenase, microbial growth and inflammation, and currently demands the generation of toxicity data. The purpose of this study was to examine the toxicities of the single and 14 days repeated dose toxicity in Sprague-Dawley rats orally administrated with plantamajoside at dose levels of 0, 500, 1000, and 2000 mg of dried material/kg body weight/day. The results showed that there was no difference in body weight change, food intake, water consumption, or relative organ weight among different dose groups. Also we observed no death and abnormal clinical signs were observed during the experimental period. Between the groups orally administered Plantago asiatica and the control group, there was no statistical significance in hematological test or serum biochemical values. There were no gross findings at final sacrifice. There was no evidence of histopathological alteration mediated by 14 days treatment with Plantago asiatica. These results suggest that no observed adverse effect level (NOAEL) of the oral application was considered to be more than 2000 mg/kg in rats under the conditions employed in this study. Another observation was performed to investigate the safety of Plantago asiatica in respect of genotoxicity. This substance was examined that Salmonella typhimurium reversion assay (Ames test) in strain TA98, TA100, TA1535. In the reverse mutation test, Plantago asiatica did not induce mutagenicity in Samonella typhimurium with and without metabolic activation. These results indicated that Plantago asiatica had no genotoxicity.

28days Repeat Oral Dose Toxicity Test of 'Hyeonggaeyeongyotang' extract in SD Rats (형개련교탕(荊芥連翹湯) 추출물(抽出物)의 SD Rats에서 28일 경구(經口) 반복투여 독성시험)

  • An, Hyun-Jue;Hwang, Sun-Yi;Lee, Jong-Rok;Kim, Sang-Chan;Jee, Seon-Young
    • Herbal Formula Science
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    • v.16 no.1
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    • pp.147-168
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    • 2008
  • HYTE (Hyeonggaeyeongyotang Extract), a polyherbal formula has been used as folk medicine, 28days repeat oral dose toxicity was tested in SD rats according to KFDA Guideline[2005-60]. Methods : In this study, mortality, clinical signs, body weight and gains, food and water consumption, ophthalmologic observation, urinalysis, hematology, serum biochemistry, gross findings, organ weight and histopathological observations were conducted during 28days of dosing periods. Results: 1. No HYTE treatment-related mortalities and clinical signs were detected in all dosing levels tested in male and female rats during the whole experimental periods. 2. No HYTE treatment-related changes on body weight, gains and food consumption were detected in all dosing levels tested in male and female rats during the whole experimental periods except for 2000mg/kg-dosing female groups in which significantly increase of body weight, gains, food and water consumption were detected compared to that of vehicle control in some points. 3. No HYTE treatment-related changes on ophthalmologic examination were detected in all dosing levels tested in male and female rats. 4. No HYTE treatment-related changes on urinalysis were detected in all dosing levels tested in male and female rats except for 2000mg/kg-dosing female groups in which, significantly increase of urine volume and related decrease on the urine specific gravity were detected as secondary effects of increase on the water consumptions not HYTE treatment-related toxicological signs. 5. No HYTE treatment-related changes on hematology were detected in all dosing levels tested in male and female rats except for increases in the total WBC count and lymphocytes of 2000mg/kg-dosing male and female groups with decrease of large unstained cells as pharmacological effects of immune enhancements not HYTE treatment-related toxicological signs. 6. No HYTE treatment-related changes on serum biochemistry were detected in all dosing levels tested in male and female rats. 7. No HYTE treatment-related changes on gross findings, organ weight and histopathology were detected in all dosing levels tested in male and female rats except for 2000mg/kg-dosing male and female groups in which, spleen and thymus organ weights, hypertrophy at gross observation and hyperpalsia of lymphoid cells and follicles at histopathological observation in spleen and thymus were detected as pharmacological effects of immune enhancements not HYTE treatment-related toxicological signs. Conclusions : Based on these results, the NOAEL and MTD of HYTE in SD rats were considered as over 2000mg/kg, respectively at 28days repeat oral dose toxicity test because most of these findings were considered as results of pharmacological effects of immune enhancements not HYTE treatment-related toxicological signs or secondary effects.

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Simultaneous determination and acute toxicity study of Fructus mume extracts in ICR mice (오매(烏梅)의 다성분동시분석 및 마우스를 이용한 경구 단회투여 급성독성시험)

  • Lee, In-Sun;Han, Chang-Hyun;Lee, Chul;Hwang, Bang-Yeon;Jung, Sang-Hyeok;Lee, Young-Joon;Jeon, Won-Kyung
    • Journal of Society of Preventive Korean Medicine
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    • v.15 no.1
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    • pp.37-47
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    • 2011
  • Objectives : Previous studies have shown that Fructus mume (FM) has anti-platelet effects. The present study was performed to determine the acute oral toxicity and quality control of a crude extract of FM in ICR mice. Methods : We investigated the in vivo single dose acute toxicity of FM 95% ethanol extract. This test was orally administered once by gavage to 20 male and 20 female mice at dose levels of 0 (control group), 1250, 2500 and 5000mg/kg body weight, respectively. Mortalities, clinical findings, autopsy findings and body weight changes were monitored daily for the 14 days following the administration. HPLC analysis was performed for the simultaneous determination of ursolic acid and p-hydroxycinnamic acid in FM. Reverse-phase chromatography using a C18 column and photodiode array detection at 211 nm was used for quantification of the two maker components. The mobile phase for gradient elution consists of water and acetonitrile. Results : We observed survival rates, general toxicity, change of body weight, and autopsy. The mice did not die after single oral administration of maximum dose of FM. Autopsy of animal revealed no abnormal gross finding. Therefore, $LD_{50}$ value of FM for ICR mice was more than 5000mg/kg on oral route. The HPLC analysis showed that ursolic acid and p-hydroxycinnamic acid amounts to 9.75- and 0.12% in the extract with the retention times of 47.99- and 15.38 minutes, respectively. Conclusions : These results suggest that no toxic dose level of FM in mice is considered to be more than 5000mg/kg. Consequently, it was concluded that FM have no effect on acute toxicity and side effect in ICR mice. For the quality control of FM extract, simultaneous determination of ursolic acid and p-hydroxycinnamic acid was established.

Single-Dose Toxicity and Four Week Repeated-Dose Toxicity Study on Tensolin-F® (3,9-diferuloyl-6-oxopterocarpen) (Tensolin-F® (3,9-diferuloyl-6-oxopterocarpen)의 단회 독성시험 및 4주 반복투여 독성시험)

  • Kim, Keun-Su;Park, Sung-Min;Lee, Nam-Jin;Pyo, Hyeong-Bae;Chai, Hee-Yul;Jung, Yu-Ri;Lin, Chun-Mai;Kim, Sun-Hee;Lee, Hye-Young;Kang, Jong-Koo
    • Toxicological Research
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    • v.23 no.4
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    • pp.405-413
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    • 2007
  • This study was to investigate single and repeated-dose toxicities of Tensolin-$F^{(R)}$, an anti-wrinkle agent, in Sprague-Dawley (SD) rats or ICR mice. In single-dose oral toxicity study, the test materials were administered once by gavage to male and female SD rats at dose levels of 0 and 2,000 mg/kg. No dead animals and abnormal necropsy findings were found in control and Tensolin-$F^{(R)}$ treated group. Therefore, the approximate lethal dose of Tensolin-$F^{(R)}$ was considered to be higher than 2,000 mg/kg in rats. In the 4-week repeated oral toxicity study, the test material was administered once daily by gavage to male and female ICR mice at dose levels of 0, 25, 50 and 100 mg/kg/day for 4-weeks. In the results, no abnormality was observed in mortality, clinical findings, body weight changes, food and water consumptions, opthalmoscopic findings, necropsy findings, histopathological findings. In hematological analysis, there was a trend of increase in reticulocyte at male 25 mg/kg, although such changes were in normal ranges. On the other hand, there was a trend of decrease in hemoglobin at female 50, 100 mg/kg, such changes were in normal ranges. In addition, serum biochemical parameters including sodium, BUN and chloride increased at 25, 50 and 100 mg/kg. Relative organ weights of right testis, brain, lung and left epididymis were increased in 100 mg/kg groups of male rats in contrast to not change in female groups. However, these changes of relative organ weights, hematological and serum biochemical parameters were not accompanied with related signs such as histopathological changes or clinical findings. In conclusion, 4-week repeated oral dose of Tensolin-$F^{(R)}$ to ICR mice did not cause apparent toxicological change at the dose of 25, 50, 100 mg/kg body weight. Consequently the no-observed-adverse-effect level (NOAEL) for Tensolin-$F^{(R)}$ in ICR mice following gavage for at least 4-week is higher than 100 mg/kg/day.

A Study on thinner's Physicochemical property and its effect on genital organ of rat (시너(thinner)의 물리화학적 특성과 랫트의 생식기에 미치는 영향 연구)

  • Kim, Hyeon-Yeong;Lee, Sung-Bae;Han, Jeong-Hee;Kim, Tae-Gyun;Lee, Jung-Suk;Kang, Min-Gu;Lee, Chae-Kwan
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.18 no.3
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    • pp.224-238
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    • 2008
  • The aim of this study is to confirm the physicochemical property and hazard of thinner (012), which is a diluent of enamel paint used for floor coating for waterproofing and oil painting for the outer wall. The literatures of physicochemical property and hazard of thinner were surveyed and its physicochemical property were evaluated. And then, the inhalation toxicity of thinner affecting the central nervous system and reproductive organs in rats were examined by subchronic (6 h./day. 5 days/ week for 13 weeks) inhalation test. 1) According to the 13-week subchronic inhalation test, there were no significant changes in clinical test and body weight. However, a significant evidence of toxicity was observed in the hematological test and organ weight such as heart, kidney, liver and brain (p<0.01) in the 200 ppm and 1,000 ppm exposure groups in a dose response manner. In the histopathology analysis, there were no significant evidence of toxicity. Therefore, thinner was not classified as an organ targeted toxic agent. In case of Harmfulness, it could be classified as a chronic toxic agent 3($500 ppm/4hr, rat). 2) The reproductive toxicity such as extension of the period of estrous cycle, reduction of serum estradiol concentration and increase of frequency of the abnormal sperm was observed in the 1,000 ppm exposed animals. 3) The result of the physicochemical property of the test material showed that the specific gravity was 0.793, boiling point $155.8^{\circ}C$, steam pressure 2.1 kPa, ignition point $34.5^{\circ}C$, and spontaneous ignition point $280^{\circ}C$. The endothermic and exothermic values were 371.4 J/g and 159.1 J/g. respectively. The explosion limit was 214 mg/l. These data showed that thinner could be classified as an explosion agent level 1.2 and ignitive liquid agent 3 ($23-60^{\circ}C$) according to the notification No. 2008-1 of the Labor Ministry, "Classifying Standard of Chemical Materials."

Embryonic Zebrafish Model - A Well-Established Method for Rapidly Assessing the Toxicity of Homeopathic Drugs - Toxicity Evaluation of Homeopathic Drugs Using Zebrafish Embryo Model -

  • Gupta, Himanshu R;Patil, Yogesh;Singh, Dipty;Thakur, Mansee
    • Journal of Pharmacopuncture
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    • v.19 no.4
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    • pp.319-328
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    • 2016
  • Objectives: Advancements in nanotechnology have led to nanoparticle (NP) use in various fields of medicine. Although the potential of NPs is promising, the lack of documented evidence on the toxicological effects of NPs is concerning. A few studies have documented that homeopathy uses NPs. Unfortunately, very few sound scientific studies have explored the toxic effects of homeopathic drugs. Citing this lack of high-quality scientific evidence, regulatory agencies have been reluctant to endorse homeopathic treatment as an alternative or adjunct treatment. This study aimed to enhance our insight into the impact of commercially-available homeopathic drugs, to study the presence of NPs in those drugs and any deleterious effects they might have, and to determine the distribution pattern of NPs in zebrafish embryos (Danio rerio). Methods: Homeopathic dilutions were studied using high-resolution transmission electron microscopy with selected area electron diffraction (SAED). For the toxicity assessment on Zebrafish, embryos were exposed to a test solution from 4 - 6 hours post-fertilization, and embryos/larvae were assessed up to 5 days post-fertilization (dpf ) for viability and morphology. Toxicity was recorded in terms of mortality, hatching delay, phenotypic defects and metal accumulation. Around 5 dpf was found to be the optimum developmental stage for evaluation. Results: The present study aimed to conclusively prove the presence of NPs in all high dilutions of homeopathic drugs. Embryonic zebrafish were exposed to three homeopathic drugs with two potencies (30CH, 200CH) during early embryogenesis. The resulting morphological and cellular responses were observed. Exposure to these potencies produced no visibly significant malformations, pericardial edema, and mortality and no necrotic and apoptotic cellular death. Conclusion: Our findings clearly demonstrate that no toxic effects were observed for these three homeopathic drugs at the potencies and exposure times used in this study. The embryonic zebrafish model is recommended as a well-established method for rapidly assessing the toxicity of homeopathic drugs.

Aquatic Toxicity Assessment of Phosphate Compounds

  • Kim, Eunju;Yoo, Sunkyoung;Ro, Hee-Young;Han, Hye-Jin;Baek, Yong-Wook;Eom, Ig-Chun;Kim, Hyun-Mi;Kim, Pilje;Choi, Kyunghee
    • Environmental Analysis Health and Toxicology
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    • v.28
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    • pp.2.1-2.7
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    • 2013
  • Objectives Tricalcium phosphate and calcium hydrogenorthophosphate are high production volume chemicals, mainly used as foodstuff additives, pharmaceuticals, lubricants, synthetic resin, and disinfectants. Phosphate has the potential to cause increased algal growth leading to eutrophication in the aquatic environment. However, there is no adequate information available on risk assessment or acute and chronic toxicity. The aim of this research is to evaluate the toxic potential of phosphate compounds in the aquatic environment. Methods An aquatic toxicity test of phosphate was conducted, and its physico-chemical properties were obtained from a database recommended in the Organization for Economic Cooperation and Development (OECD) guidance manual. An ecotoxicity test using fish, Daphnia, and algae was conducted by the good laboratory practice facility according to the OECD TG guidelines for testing of chemicals, to secure reliable data. Results The results of the ecotoxicity tests of tricalcium phosphate and calcium hydrogenorthophosphate are as follows: In an acute toxicity test with Oryzias latipes, 96 hr 50% lethal concentration ($LC_{50}$) was >100 (measured:>2.14) mg/L and >100 (measured: >13.5) mg/L, respectively. In the Daphnia test, 48 hr 50% effective concentration ($EC_{50}$) was >100 (measured: >5.35) mg/L and >100 (measured: >2.9) mg/L, respectively. In a growth inhibition test with Pseudokirchneriella subcapitata, 72 hr $EC_{50}$ was >100 (measured: >1.56) mg/L and >100 (measured: >4.4) mg/L, respectively. Conclusions Based on the results of the ecotoxicity test of phosphate using fish, Daphnia, and algae, $L(E)C_{50}$ was above 100 mg/L (nominal), indicating no toxicity. In general, the total phosphorus concentration including phosphate in rivers and lakes reaches levels of several ppm, suggesting that phosphate has no toxic effects. However, excessive inflow of phosphate into aquatic ecosystems has the potential to cause eutrophication due to algal growth.

4-week dose range finding toxicity test of Magnoliae Flos extract in Sprague-Dawley rats (Sprague-Dawley 랫드를 이용한 신이 추출물의 4주 반복 용량 결정 독성시험)

  • Park, Ju-Hyoung;Ahn, Eun-Kyung;Park, Kitae;Hwang, Min Hee;Cho, Young-Rak;Lee, Dong-Ryung;Choi, Bong-Keun;Oh, Joa Sub
    • Journal of Applied Biological Chemistry
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    • v.65 no.1
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    • pp.43-48
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    • 2022
  • Medicinal herb demonstrated in many pharmacological effects and recognized to be safe has been used for a long time. However, side effects including safety of medicinal herb have not been identified yet. The aim of the study was to estimate safety evaluation of Magnoliae Flos used for the treatment of pain, rhinitis, and pneumonia in Korea, China and Japan through four-week dose range finding toxicity test in male and female Sprague-Dawley rats. Magnoliae Flos was orally administered to male and female SD rats once a day for 28 days at 1,500 and 3,000 mg/kg. The safety evaluation was determined to examine clinical signs, mortality, body weight, food intake, hematology, serum biochemistry and relative organ weights and there were no significant changes related toxicity. Consequently, these findings indicates that Magnoliae Flos did not show any side effects including toxicity in dose range finding toxicity test and the no observed adverse effect level for Magnoliae Flos was estimated as more than 3,000 mg/kg.