scholarly journals Acute and Subacute Oral Toxicity of Mumefural, Bioactive Compound Derived from Processed Fruit of Prunus mume Sieb. et Zucc., in ICR Mice

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1328
Author(s):  
Jungim Kim ◽  
Mira Han ◽  
Won Kyung Jeon

Mumefural is a bioactive compound derived from the processed fruit of Prunus mume Sieb. et Zucc., a traditional health food; however, its safety has not been evaluated. We investigated the toxicity of mumefural through single and repeated oral administration at doses of 1250, 2500, and 5000 mg/kg in Institute of Cancer Research (ICR) mice. The acute toxicity assessment was not associated with adverse effects or death. Similarly, the subacute (four weeks) toxicity assessment did not reveal any mumefural-associated mortality, abnormal organ damage, or altered clinical signs, body weight, food consumption, or hematological parameters. However, albumin/globulin ratio and chloride ion levels were significantly increased in male mice treated with mumefural at ≥2500 mg/kg. Female mice exhibited significantly higher levels of chloride, sodium, and potassium ions, at a dose of 5000 mg/kg. Furthermore, the administration of 2500 and 5000 mg/kg mumefural decreased the absolute weight of spleen in male mice. These findings indicated that the approximate lethal dose of mumefural in ICR mice was >5000 mg/kg. No significant mumefural toxicity was observed at ≤5000 mg/kg. Our findings provide a basis for conducting future detailed studies to evaluate reproductive, neurological, genetic, and chronic toxicity of mumefural.

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Kyungjin Lee ◽  
Ho-Young Choi

Studies on the safety of herbal medicine are essential for the development of new drugs. The aim of this study was to evaluate the no-observed-adverse-effect-level (NOAEL) of HVC1 (Gamisamhwangsasim-tang, a 30% ethanol extract of a mixture of Pruni Cortex, Scutellariae Radix, Coptidis Rhizoma, and Rhei Rhizoma) and identify its target organs after oral administration to Sprague-Dawley (SD) rats repeatedly for 13 weeks. Three test groups were treated with HVC1 at a dose of either 500 (low-dose), 1,000 (middle-dose), or 2,000 (high-dose) mg/kg/day. Another group received high-dose HVC1 and was observed for 4 weeks following treatment to examine recovery from the effects of the extract. All treatment groups were compared to a vehicle control group. During the study, mortality, clinical signs, body weight changes, food consumption, abnormal lesions in the eye, urinary parameters, hematological parameters, blood coagulation time, blood biochemical parameters, changes in organ weight, gross findings, and histopathological changes were examined. No systemic toxicity related to HVC1 was observed in any group, and it was concluded that the NOAEL of HVC1 was 2,000 mg/kg/day. No target organ was identified.


2021 ◽  
Vol 36 (3) ◽  
pp. e2021019
Author(s):  
Ja Kyung Seol ◽  
Myeongkyu Park ◽  
Jae Min Im ◽  
Heung Sik Seo ◽  
Hee Ju Park ◽  
...  

TiO2 was a photocatalyst that used to the most common product because of the high efficiency. TiO2 (P-25, commercial nanomaterial product) is the most typical photocatalyst product and TiO2 (GST) was a sludge recycling product. This study was reported to evaluate an acute toxicity of TiO2 (P-25 and GST) according to OECD test guideline 402 and 423 in Sprague-Dawley (SD) female rats via route of oral and dermal. There was investigated the lethal dose (LD50), and mortality, clinical signs, body weight changes and gross findings were continually monitored for 14 days following the single administration. After administration, TiO2 (P-25) was calculated that LD50 was considered to be a dose of over 2000 mg/kg body weight for both different route of exposure, and TiO2 (GST) was the same. Other items were no observed an adverse effect between P-25 and GST; no mortality and clinical signs, accidental body weight loss, no gross findings. On the basis of the above results, the toxicity of the GST was almost equal to that of the commercial product, P-25 and there was no toxicological evidence.


2020 ◽  
Vol 9 (4) ◽  
pp. 484-492
Author(s):  
Sini Kang ◽  
Tony V Johnston ◽  
Seockmo Ku ◽  
Geun Eog Ji

Abstract B-FOS (butyl-fructooligosaccharide) is a newly synthesized prebiotic molecule, formed by the combination of FOS and butyrate by ester bonds. B-FOS has been reported to have the potential prebiotic effect of promoting intestinal flora diversity and enhancing butyrate production. The aim of this study was to investigate the potential acute and sub-chronic toxicity of B-FOS in Institute of Cancer Research (ICR) mice and Wistar rats to verify its biosafety. ICR mice were administered a single oral gavage of B-FOS at doses of 0, 500, 1000, and 2000 mg/kg body weight and observed for signs of acute toxicity for 14 days. Sub-chronic toxicity was evaluated by repeated oral administration of B-FOS at 2000 mg/kg for 28 days, in accordance with Organization for Economic Co-operation and Development (OECD) protocol test numbers 420 and 407. No mortality or abnormal clinical signs were observed during the experimental periods after B-FOS administration. Furthermore, no significant changes in body weight, organ weight, serum biochemical parameters, or tissue histology were observed after animal sacrifice. These in vivo results indicate that B-FOS does not exert any acute or sub-chronic toxicity at a dose of 2000 mg/kg, and this novel molecule can be regarded as a safe prebiotic substance for use in the food and nutraceutical industries.


Author(s):  
SURADWADEE THUNGMUNGMEE ◽  
NAKUNTWALAI WISIDSRI

Objective: This study aimed to assess the toxicity of Trapa bispinosa Roxb. starch (TBS) through in vitro and in vivo studies.Methods: The cytotoxicity of TBS extract (TBSE) was evaluated on RAW 264.7 macrophage and NIH 3T3 fibroblast cell lines and the acute dermal andoral toxicities of TBS were analyzed in rats. To access acute dermal toxicity, the rats received a single application of 200, 1000, and 2000 mg/kg BW ofTBS, while for acute oral toxicity, the rats received a single administration of 300 and 2000 mg/kg BW of TBS. All animals were observed for changesin body weight, mortality, and clinical signs of abnormality after application and administration of the TBS.Results: The in vitro results showed that TBSE at concentrations of 6.25–200 μg/ml was non-cytotoxic to macrophages and fibroblasts. From acutetoxicity studies, the lethal dose of TBS was considered to be over 2000 mg/kg BW. No mortality, clinical signs of abnormality, or gross pathology weredetected at necropsy.Conclusion: TBS is non-toxic in in vitro and in vivo studies. Therefore, TBS can be used as pharmaceuticals excipients or cosmetic ingredients.


2020 ◽  
Vol 8 (A) ◽  
pp. 76-83 ◽  
Author(s):  
Rudy Agung Nugroho ◽  
Retno Aryani ◽  
Hetty Manurung ◽  
Rudianto Rudianto ◽  
Widha Prahastika ◽  
...  

BACKGROUND: Ficus deltoidea Jack. leaves have a great potential as traditional medicine, but the safety level of its use is still unknown. AIM: This study aimed to determine the phytochemical contents of the ethanol extract of F. deltoidea leaves and evaluate the level of safety and toxicity through acute and subchronic toxicity tests in mice (Mus musculus). METHODS: The ethanol extract of F. deltoidea leaves was determined for phytochemical contents such as alkaloids, phenolics, flavonoids, coumarin, steroids, saponins, carotenoids, and tannins. In the acute toxicity test, 10 male mice were divided into a control group and the extract treatment group with 2000 mg/kg body weight (BW) dose for 14 days to identify signs of toxicity and mortality. Meanwhile, in the subchronic toxicity test, 25 male mice were divided into control and four treatment groups with various doses (125, 250, 500, and 1000 mg/kg BW), respectively, for 28 days. The toxicological effect was evaluated by observing behavior, signs of toxicity, and changes in BW. At the end of the treatment, hematological and biochemical evaluations were also measured. RESULTS: The results showed that the ethanol extract of F. deltoidea Jack leaves qualitatively contains alkaloids, phenolic, flavonoids, coumarin, and steroids, whereas quantitatively total phenolics, flavonoids, and IC50 were 107.6583211 μg GA/mg, 175.9103641 μg CE/mg, and 103.7484 μg/mL. Moreover, 2000 mg/kg BW dose resulted in no symptoms of toxicity and mortality, indicating that the 50% lethal dose (LD50) was above 2000 mg/kg BW. Meanwhile, there were no behavioral changes, significant differences in weight changes, hematological parameters, and serum biochemistry of mice in subchronic toxicity tests. CONCLUSION: The present study shows that acute and subchronic oral administration of the ethanol extract of F. deltoidea leaves for male mice does not induce clinical symptoms of toxicity or mortality. The LD50 of the ethanol extract of F. deltoidea leaves for mice >2000 mg/kg is considered as practically non-toxic.


Author(s):  
Mariam Traore ◽  
Adjaratou C. Coulibaly ◽  
Kadiatou T. Traore ◽  
Abdoul G. L. Boly ◽  
Esther W. L. M. B. Kabre ◽  
...  

Aims: The aim of this study was to evaluate the anti-inflammatory and analgesic activities of Daniellia oliveri methanolic extract and its fractions in NMRI mice. Study Design: In vivo acute toxicity, anti-inflammatory and analgesic assays. Place and Duration of Study: The work was carried out in the Department of Traditional Pharmacopoeia and Pharmacy (MEPHATRA / PH) of the Research Institute for Health Sciences (IRSS) Ouagadougou (Burkina- Faso) between December 2020 and February 2021. Methodology: The toxicity of the extracts was assessed according to OECD guideline 423 of 2001 at a single dose of 2000 mg / kg body weight. Analgesic effect was evaluated on the number of abdominal contortions induced by the intraperitoneal injection of acetic acid and the anti-inflammatory activity using the Carrageenan anti-edematous test was determined according to Winter. Results: The results of the acute oral toxicity study in mice showed no clinical signs of toxicity at dose of 2000 mg/kg b.w. The lethal dose (LD50) value estimated to 5000 mg/kg. The extracts reduced edema from the first hour, then by the third hour and maximum inhibition was achieved by the fifth hour after the injection of carrageenan. Extract and methanolic fraction at different doses showed significant inhibition of abdominal contortions in mice in a dose dependent manner. At 200mg the analgesic effect of methanolic fraction and crude extract was 53.70±1.29% and 41.38±1.25% respectively. At 400 mg/kg, the methanolic fraction inhibited carragenaan-induced edema by 85.97±5.67%. Conclusion: Daniellia oliveri is an important source of anti-inflammatory and analgesic compounds, justifying the use of this plant in traditional medicine for the treatment of inflammatory diseases.


2020 ◽  
Vol 44 (1) ◽  
pp. 46-56
Author(s):  
Ahmad H. Al-Zuhairi

Calotropis procera it is announced to be medicinal and poisonous plant to human and animals. A toxicological effects of aqueous leaves extract evaluated experimentally in rabbits. The median lethal dose (LD50) was estimated (2435.25 mg/kg) by using the Up and Down method. Twenty-five local breed rabbits, of 1-2 years old, 1-1.9 kg b. wt. Divided randomly into five groups, five rabbits of each. Those of groupsI, II, III and IV were exposed to 1/10 of LD50 (243.5mg/kg), 1/12.5 of LD50 (194.8), 1/15 of LD50(162.4),1/20 of LD50 (121.8) mg/kg. b.w. of extract respectively for 8 weeks, while those in G.V were left without exposed as a control group. Alkaloids, saponins, tannins, cardiac glycosides, steroidal, glycoside, terpenoids and flavonoids detected in phytochemicals screening. The dependent parameter were clinical signs exhibited by animals during the study in addition to some hematological parameters Red blood cells (RBC) count, hemoglobin (Hb) concentration and packed cell volume (PCV). The main changes observed during monitoring the animals were chewing of mouth, bradycardia, engorged blood vessels, coughing and depression especially in these of G I, II and III; diminution body weight in G I; abortion in G I and II. The hematological and biochemical parameters depended showed a significant increase during the study. From this we can concluded that aqueous extract of leaves of the plant has a harmful effect in rabbits.


2020 ◽  
pp. 31-32
Author(s):  
Mikhail A. Levchenko ◽  
◽  
Natalia A. Sennikova ◽  

Toxicological assessment is a mandatory research step in the development of new insecticidal drugs. At the All-Russian Research Institute of Veterinary Entomology and Arachnology, a prototype of the insecticidal bait Mukhnet IF was obtained with an active ingredient content of 0.06% ivermectin and 0.015% fipronil, which showed a highly effective effect against houseflies. This work presents the results of the study of acute oral toxicity of the above agent. For this, male white mice with a live weight of 16-26 g were selected. They were kept on a starvation diet for one day in individual houses with water. The drug was given in mg/kg body weight the next day. A total of 33 doses have been tested, ranging from 100 mg/kg to 40,000 mg/kg. The animals were observed for 14 days. According to the research results, it was revealed that at doses up to 20,000 mg/kg there were no signs of intoxication, but when tested at 25,000 mg/kg in some mice, these signs were noted, and at 30,000, 35,000 and 40,000 mg/kg deaths were recorded 20±10, 45±30 and 60±20%, respectively. It was not possible to test the drug over the last above dose due to incomplete eaten by mice. According to the degree of danger for warm-blooded animals, the drug belongs to the 4th class of low-hazard drugs (average lethal dose of 5000 mg/kg or more) in accordance with the classification of GOST 12.1.007-76. When analyzing the literature data on the toxicological characteristics of preparations containing ivermectin and chlorfenapyr, it was revealed that the insecticidal agent in its acute toxicity for warm-blooded animals is comparable to known analogues.


2019 ◽  
Vol 9 (3) ◽  
pp. 207-216
Author(s):  
Lalit Sharma ◽  
Aditi Sharma ◽  
Girdhari L. Gupta ◽  
Gopal Singh Bisht

Background: A standardized polyherbal preparation (POL-6) containing six plant extracts Hypericum perforatum, Bacopa monnieri, Centella asiatica, Withania somnifera, Ocimum sanctum and Camellia sinesis have good antioxidant, anti-inflammatory, and immunomodulatory activities. The present study was carried out to evaluate the safety profile of POL-6 through acute and subacute oral toxicity models in Wistar rats. Methods: In acute safety evaluation, a single dose of 2000mg/kg of POL-6 was given orally to five rats and was observed for 14 days. In subacute safety evaluation POL-6 at the doses of 250, 500 and 1000 mg/kg was given orally to the rats once a day for 28 days. The animals were observed for the signs of toxicity and mortality during the study period. Results: In acute toxicity evaluation, POL-6 treatment did not show any toxic signs and mortality in animals during the observation period. In subacute toxicity studies, no changes were seen in any of the dose levels of POL-6 treatment during the total body weights, organ weights and hematobiochemical parameters examination of the rats. No lesions were seen during the gross/histopathological examination. Conclusion: The study revealed that administration of POL-6 for 28 days showed no significant treatment generated toxic effects in the animals, hence it can be considered as non-toxic if it is ingested in a time not greater than a month.


1987 ◽  
Vol 21 (3) ◽  
pp. 226-232 ◽  
Author(s):  
C. J. Trahan ◽  
E. H. Stephenson ◽  
J. W. Ezzell ◽  
W. C. Mitchell

To evaluate the efficacy of a commercial bacterial vaccine in protecting Strain 13 guineapigs against fatal Bordetella bronchiseptica pneumonia, it was necessary to establish the infectivity and disease pathogenesis induced by virulent organisms. When guineapigs were exposed to small-particle aerosols of varying concentrations of virulent B. bronchiseptica, a spectrum of disease was produced that ranged from inapparent illness to fulminant bronchopneumonia. Clinical signs began by day 4 after exposure, and were evidenced by anorexia, weight loss, respiratory distress and serous to purulent nasal discharge. Pathological alterations were limited to the respiratory system. Moribund animals exhibited a suppurative necrotizing bronchopneumonia and necrotizing tracheitis. In animals that survived the challenge, the bacteria were eliminated from the lungs by day 28 but continued to persist in the laryngeal area and the trachea. The median infectious dose and the median lethal dose were estimated to be 4 colony-forming units (CFU) and 1314 CFU respectively. These data suggest that the guineapig will be a valuable model system in which to study interactions between Bordetella species and host cells as well as to evaluate potential B. bronchiseptica immunogens.


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