scholarly journals Acute and sub-chronic (28-day) oral toxicity profiles of newly synthesized prebiotic butyl-fructooligosaccharide in ICR mouse and Wistar rat models

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.

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 684-684
Author(s):  
Maria Amelita Estacio ◽  
Liezl Atienza ◽  
Roxanne Gapasin ◽  
Jonna Rose Maniwang ◽  
James Ryan Aranzado ◽  
...  

Abstract Objectives “Bignay” (Antidesma bunius), “lipote” (Syzygium polycephaloides) and “duhat” (Syzgium cumini) are indigenous berries in the Philippines that are known to contain high antioxidant properties and other health-promoting and disease-preventing compounds. However, oral toxicity studies on these berries are not yet explored. Hence, this study evaluated the acute oral toxicity of these berries in freeze-dried forms using 6-week old ICR mice following the OECD guidelines 425 (up and down method). Methods Treatment groups were administered with freeze-dried powders of “bignay”, “lipote” and “duhat” reconstituted in distilled water at various doses: 55 mg/kg body weight (BW), 175 mg/kg BW, 550 mg/kg BW, 2000 mg/kg BW and 5000 mg/kg BW while control group was administered with distilled water. Body weight, feed and water intake were obtained daily. Biochemical profiles were measured prior to administration of reconstituted berries at day 1 and prior to euthanasia. Toxicity, morbidity and mortality cases were observed daily. Euthanasia and necropsy were performed to check for gross organ abnormalities. Results Mice that received the different concentrations of “bignay”, “lipote” and “duhat” had normal feed and water consumption and gained weight during the test period. No clinical and behavioral signs of toxicity were observed and there was zero morbidity and mortality. Post-mortem evaluation showed no lesions on various organs examined. Blood ALT, BUN and creatinine levels were within normal published values. Conclusions These results show that different concentrations of freeze-dried “bignay”, “lipote” and “duhat” are non-toxic using ICR mice and therefore have high potential to be developed into food supplements and nutraceuticals. Funding Sources Philippine Council for Health Research and Development - Department of Food Science and Technology Enhanced Creative Work and Research Grant - Office of Vice Chancellor for Academic Affairs, University of the Philippines.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jyoti Kaushik ◽  
Simran Tandon ◽  
Rishi Bhardwaj ◽  
Tanzeer Kaur ◽  
Surinder Kumar Singla ◽  
...  

Abstract Modern treatment interventions for kidney stones are wrought with side-effects, hence the need for alternative therapies such as plant-based medicines. We have previously documented through in vitro studies that statistically optimized aqueous extract of Tribulus terrestris (Zygophyllaceae family) possesses antiurolithic and antioxidant potential. This provides strong scientific foundation to conduct in vivo efficacy and preclinical safety studies to corroborate and lend further proof to its ability to prevent and cure kidney stones. The preventive and curative urolithiatic efficacy in experimentally induced nephrolithiatic Wistar rats, along with preclinical toxicity was evaluated following oral administration of statistically optimized aqueous extract of T. terrestris. Treatment showed augmented renal function, restoration of normal renal architecture and increase in body weight. Microscopic analysis of urine revealed excretion of small sized urinary crystals, demonstrating that treatment potentially modulated the morphology of renal stones. Tissue enzymatic estimation affirmed the antioxidant efficacy of treatment with reduced free radical generation. Significant upregulation of p38MAPK at both the gene and protein level was noted in hyperoxaluric group and interestingly treatment reversed it. Acute oral toxicity study established the Median Lethal Dose (LD50) to be greater than 2000 mg/kg body weight (b.wt.) No observed adverse effect level (NOAEL) by repeated oral toxicity for 28 days at 750 mg/kg b.wt. was noted. This study lends scientific evidence to the safe, preventive and curative potential of statistically optimized aqueous extract of T. terrestris at a dose of 750 mg/kg b.wt. and suggests that the extract shows promise as a therapeutic antiurolithic agent.


2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Nasreddine El Omari ◽  
Omar El Blidi ◽  
Abdelhakim Bouyahya ◽  
Karima Sayah ◽  
Saad Bakrim ◽  
...  

Aristolochia longa L. (Aristolochiaceae) is an herbaceous plant recognized in alternative medicine for its many therapeutic virtues. The aim of this study was to determine the pharmacotoxicological effects of this plant in order to ensure safe clinical use. The oral toxicity of the aqueous extract of A. longa roots was performed in vivo on Wistar rats at doses of 0.8, 1.25, 2, 2.5, and 5 g/kg/day for 21 days. Clinical signs were observed throughout the experimental period, followed by measurement of body weight change, while selected biochemical parameters, as well as relative organ weights and the histology of liver, kidney, and intestinal tissues, were evaluated after 6, 11, and 16 days and then at the end of 21 days of daily administration. At repeated doses for 21 days, the extract contributed to significant weight gain, in both control and treated rats. The global analysis of hepatic and renal biomarkers showed a significant increase between control and different doses of the extract, from the first to the third week of treatment, indicating the likely toxic effect of the extract on liver and kidney function. Organ toxicity was confirmed by histopathological examination, which revealed greater renal and hepatic parenchymal changes in animals treated with a high dose beyond the 16th day. At the end of the treatment, relatively small size of intestinal villi was also observed. It was concluded that ALAE has a low toxicity potential in nonprolonged oral administrations. However, at high chronic oral doses, A. longa appears to have significant toxicity on the organs tested.


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 39 (2) ◽  
pp. 212-223 ◽  
Author(s):  
CA Otuechere ◽  
A Adewuyi ◽  
OL Adebayo ◽  
IA Ebigwei

Chemical modification of cellulose is currently attracting attention as researchers attempt to take advantage of the abundance of hydroxyl groups on its surface to introduce extra biological functionality. However, the possible deleterious effect of exposure to functionalized nanocellulose (CSN) remains a concern. Therefore, this study aims to explore the potential mechanisms of hepatotoxicity of CSN modified with oxalate ester (NCD) in rats. A 7-day repeated oral toxicity study of NCD at the doses of 50 and 100 mg kg−1 body weight was conducted, and plasma and liver tissue samples were assayed using biochemical analysis, liver histopathology, and protein expression. NCD, at both doses, did not significantly ( p > 0.05) alter the relative weight of liver, alkaline phosphatase activity, and lipid peroxidation levels of the animals. However, NCD at the dose of 100 mg kg−1 body weight significantly elevated aspartate aminotransferase, alanine aminotransferase, and myeloperoxidase activities. NCD also enhanced the immunohistochemical expression of inducible nitric oxide synthase and Bcl-2-associated X protein in the liver of rats. Histological observations revealed necrosis and severe cellular infiltration at the high-dose treatment. Our study provides an experimental basis for the safe application of NCDs.


2007 ◽  
Vol 26 (3) ◽  
pp. 247-251 ◽  
Author(s):  
T. Ramesh ◽  
K. Lee ◽  
H. W. Lee ◽  
S. J. Kim

Acute oral toxicity of methanol extract of Asiasari radix was evaluated in ICR mice of both sexes. In this study, mice were administrated orally with dosages of 1000, 3000, and 5000 mg/kg body weight of Asiasari radix extract. Mortality, signs of toxicity, body weight, food consumption, and gross findings were observed for 14 days post treatment of Asiasari radix extract. No mortality, signs of toxicity, and abnormalities in gross findings were observed. In addition, no significant differences were noticed in the body and organ weights between the control and treated groups of both sexes. These results show that the methanol extract of Asiasari radix is toxicologically safe by oral administration.


2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Kwan Yuet Ping ◽  
Ibrahim Darah ◽  
Yeng Chen ◽  
Subramaniam Sreeramanan ◽  
Sreenivasan Sasidharan

DespiteEuphorbia hirtaL. ethnomedicinal benefits, very few studies have described the potential toxicity. The aim of the present study was to evaluate thein vivotoxicity of methanolic extracts ofE. hirta. The acute and subchronic oral toxicity ofE. hirtawas evaluated in Sprague Dawley rats. The extract at a single dose of 5000 mg/kg did not produce treatment related signs of toxicity or mortality in any of the animals tested during the 14-day observation period. Therefore, the LD 50 of this plant was estimated to be more than 5000 mg/kg. In the repeated dose 90-day oral toxicity study, the administration of 50 mg/kg, 250 mg/kg, and 1000 mg/kg/day ofE. hirtaextract per body weight revealed no significant difference (P>0.05) in food and water consumptions, body weight change, haematological and biochemical parameters, relative organ weights, and gross findings compared to the control group. Macropathology and histopathology examinations of all organs including the liver did not reveal morphological alteration. Analyses of these results with the information of signs, behaviour, and health monitoring could lead to the conclusion that the long-term oral administration ofE. hirtaextract for 90 days does not cause sub-chronic toxicity.


2020 ◽  
Vol 9 (6) ◽  
pp. 403-409
Author(s):  
S Sonitha ◽  
◽  
D Sivaraman ◽  
V Rani ◽  
◽  
...  

Medicinal plants have been used in traditional medicines for their unmatched availability of bioactive compounds. Asthma is the most common chronic disease among children worldwide. It is ranked 16th among the leading causes of years lived with disability. Medicinal plants have placed a vital role in the siddha system of medicine over centuries to cure acute and chronic illness. The aim of the present study was to investigate toxicity analysis to evaluate safety of the siddha drug Thulasi Ennai in vivo in wistar albino rats. Thulasi Ennai is a polyherbal siddha formulation mentioned in the ancient siddha books and literature, indicated to cure childhood bronchial asthma. In this study, Thulasi Ennai administered orally at a single dose of 2000mg/kg body weight and monitored for 14 days. For subacute toxicity study, Thulasi Ennai was orally administered in different doses of 200,400mg/kg body weight, daily for 28 days. At the end of each study physical parameters, hematological, biochemical and histopathological analysis were evaluated. No animals in each group of acute or subacute toxicity study showed mortality or clinical signs of toxicity throughout the study. Hence, the results of the study indicate a safe toxicological profile of Thulasi Ennai.


2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Guangcheng Dai ◽  
Chenglu Wang ◽  
Wei Tang ◽  
Jiangyun Liu ◽  
Boxin Xue

Eupatorium japonicum Thunb and Foeniculum vulgare are two of the most widely used folk herbs and constituents in many traditional Chinese herbal formulas. Nonetheless, little toxicological and safety information associated with following daily repeated exposure is obtained according to previous research. The present study was performed to assess the toxicity of ethanol extract from Eupatorium japonicum Thunb and Foeniculum vulgare (EFE) in male rats administered by dietary oral gavage at target doses of 0.39, 0.78, and 1.56 g/kg body weight/day for 90 days. There were no significant adverse effects on clinical signs, body weight, food conversion efficiency, and vital hematological indices. However, some hematology and biochemical indices such as WCV, MCH, MCHC, LY, MPV, T-CHO, as well as TG revealed significant changes in Sprague–Dawley rats and organ weights in lung and spleen showed diminished in male rats. Necropsy and histopathology findings suggested that no significant differences in absolute weights were found in all organs except lung and spleen, and no treatment-related alteration was identified in any organs. All results obtained in the present study indicated that the proper use of EFE in traditional medicine at oral dosages up to 1.56 g/kg/day body weight may harbor no prolonged toxicity to rats. However, further studies of EFE are still necessary to assess its oral safety in patients.


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