scholarly journals Acute and Chronic Oral Toxicity of a Partially Purified Plaunotol Extract fromCroton stellatopilosusOhba

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Chatchai Chaotham ◽  
Songpol Chivapat ◽  
Anan Chaikitwattana ◽  
Wanchai De-Eknamkul
Keyword(s):  
Chronic Toxicity ◽  
Clinical Symptoms ◽  
Lethal Dose ◽  
Blood Platelet ◽  
Oral Toxicity ◽  
Liver And Kidney ◽  
High Doses ◽  
Altered Liver ◽  
Further Development

Plaunotol, an acyclic diterpenoid with highly effective antigastric ulcer properties, has been commercially isolated from leaves ofCroton stellatopilosusOhba. This Thai medicinal plant was traditionally used in the form of crude extracts, suggesting that it is possible to administer these plaunotol-containing extracts without toxicity. To confirm its safety, the oral toxicity of a partially purified plaunotol extract (PPE) was evaluatedin vivo. The PPE was simply prepared by 95% ethanol reflux extraction followed by hexane partition. The obtained extract was analyzed and found to contain 43% w/w of plaunotol and another compound, likely a fatty acid-plaunotol conjugate that is considered a major impurity. Oral administration of PPE to ICR mice and Wistar rats was conducted to evaluate acute and chronic toxicity of the plaunotol extract, respectively. The acute toxicity study demonstrated that PPE was practically nontoxic based on its high median lethal dose value (LD50=10.25 g/kg). The chronic toxicity studies also showed the absence of mortality and clinical symptoms in all rats treated with 11–1,100 mg/kg/day of PPE during a 6-month period. Histopathological and hematological analyses revealed that altered liver and kidney function and increased blood platelet number, but only at the high doses (550–1,100 mg/kg/day). These results suggest that PPE is potentially safe for further development as a therapeutic agent in humans.

scholarly journals Acute and Subchronic Oral Toxicity Study of Gardenia Yellow E500 in Sprague-Dawley Rats

2020 ◽  
Vol 17 (2) ◽  
pp. 531
Author(s):  
Xiaoqiao Tang ◽  
Yangfeng Wang ◽  
Wenxiang Yang ◽  
Yanhua Zheng ◽  
Chunxia Liu ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Recovery Period ◽  
Lethal Dose ◽  
Body Weight Loss ◽  
The Body ◽  
High Dose ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Natural Colorant ◽  
Liver And Kidney

Objective: This study was conducted to evaluate the acute and subchronic toxicity of gardenia yellow, a natural colorant widely used in China and other Asian countries. An acute toxicity test was performed in S-D rats of both genders and the lethal dose (LD50) of per oral gardenia yellow was estimated to be more than 15.0 g/kg·bw. In the subchronic study, gardenia yellow was orally administered to rats by gavage at doses of 0, 0.50, 1.50 and 4.50 g/kg·bw/day for 90 days followed by a recovery period of 28 days. No appreciable toxic-related changes were observed in the 0.50 g/kg·bw/day group. When the animals received gardenia yellow at 1.50 g/kg·bw/day or more, body weight loss was observed, and pigments began to deposit in several vital organs, resulting in significant changes of several hematological and biochemical indicators related to the nutritional status of the body, liver and kidney function, more severe in the high dose group. In the recovery period, the alterations of the clinical symptoms and parameters were relieved a lot. Based on the results of the current study, the no observed adverse effect level (NOAEL) of gardenia yellow E500 in rats was set to be 0.50 g/kg·bw/day.

scholarly journals In Vivo Evaluation of the Chronic Oral Toxicity of the Marine Toxin Palytoxin

Toxins ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 489
Author(s):  
Andrea Boente-Juncal ◽  
Sandra Raposo-García ◽  
Carmen Vale ◽  
M. Carmen Louzao ◽  
Paz Otero ◽  
...  
Keyword(s):  
Oral Administration ◽  
Chronic Toxicity ◽  
Lethal Dose ◽  
Oral Toxicity ◽  
In Vivo Evaluation ◽  
Marine Toxin ◽  
Adverse Effect Level ◽  
Marine Products ◽  
Effect Level

Palytoxin (PLTX) is one of the most poisonous substances known to date and considered as an emergent toxin in Europe. Palytoxin binds to the Na+-K+ ATPase, converting the enzyme in a permeant cation channel. This toxin is known for causing human fatal intoxications associated with the consumption of contaminated fish and crustaceans such as crabs, groupers, mackerel, and parrotfish. Human intoxications by PLTX after consumption of contaminated fishery products are a serious health issue and can be fatal. Different reports have previously explored the acute oral toxicity of PLTX in mice. Although the presence of palytoxin in marine products is currently not regulated in Europe, the European Food Safety Authority expressed its opinion on PLTX and demanded assessment for chronic toxicity studies of this potent marine toxin. In this study, the chronic toxicity of palytoxin was evaluated after oral administration to mice by gavage during a 28-day period. After chronic exposure of mice to the toxin, a lethal dose 50 (LD50) of 0.44 µg/kg of PLTX and a No-Observed-Adverse-Effect Level (NOAEL) of 0.03 µg/kg for repeated daily oral administration of PLTX were determined. These results indicate a much higher chronic toxicity of PLTX and a lower NOAEL than that previously described in shorter treatment periods, pointing out the need to further reevaluate the levels of this compound in marine products.

Hepato- and Nephroprotective Effects of the Polyphenol Concentrate From Cabernet Sauvignon Grape Varieties Cultivated in Kazakhstan in the Experimental Model Of CCL4-Induced Toxicity

2017 ◽  
Vol 9 (03) ◽  
Author(s):  
Nurgozhin T. ◽  
Sergazy S. H. ◽  
Adilgozhina G. ◽  
Gulyayev A. ◽  
Shulgau Z. ◽  
...  
Keyword(s):  
Carbon Tetrachloride ◽  
Experimental Model ◽  
Lethal Dose ◽  
Radical Scavenging ◽  
Cabernet Sauvignon ◽  
Intragastric Administration ◽  
Liver And Kidney ◽  
Antioxidant Stress

Objective:This study investigates the hepatoprotective effect and the antioxidant role of polyphenol concentrate in the experimental model of carbon tetrachloride (CCl4) induced toxicity. Methods: Antioxidant activity of Cabernet Sauvignon grape polyphenol were evaluated by radical scavenging of 1,1-diphenyl-2-picryl hydrazyl radical (DPPH), 2,2’-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS.+). In addition, the effects of polyphenol concentrate on the survival of Wistar rats in the toxicity model, was also investigated. The polyphenol concentrate was administered for 5 five days prior to injection of carbon tetrachloride in a sub-lethal dose of 300 mg/kg of animal body weight in order to perform histological examinations of the liver and kidney, and detect the levels of AST, ALT and bilirubin. Results: Administration of polyphenol concentrate increased animal survival in the experimental model. Moreover, the intragastric administration of polyphenol concentrate prior to the initiation of the experimental model of toxicity, which was caused by a sub-lethal CCl4 dose, reduced morphological injuries in the liver and kidney, decreased the AST and ALT levels of the blood serum. Discussion and conclusion: Our data demonstrate that polyphenol concentrate possesses an antioxidant potential both in vitro and in vivo by reducing antioxidant stress that was caused by CCl4 administration into rats.

scholarly journals Delving into the Antiurolithiatic Potential of Tribulus terrestris Extract Through –In Vivo Efficacy and Preclinical Safety Investigations in Wistar Rats

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jyoti Kaushik ◽  
Simran Tandon ◽  
Rishi Bhardwaj ◽  
Tanzeer Kaur ◽  
Surinder Kumar Singla ◽  
...  
Keyword(s):  
Body Weight ◽  
Aqueous Extract ◽  
Kidney Stones ◽  
Wistar Rats ◽  
Lethal Dose ◽  
Tribulus Terrestris ◽  
Oral Toxicity ◽  
Preclinical Safety

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.

scholarly journals Toxicological Investigations of Aristolochia longa Root Extracts

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Nasreddine El Omari ◽  
Omar El Blidi ◽  
Abdelhakim Bouyahya ◽  
Karima Sayah ◽  
Saad Bakrim ◽  
...  
Keyword(s):  
Histopathological Examination ◽  
Global Analysis ◽  
Clinical Signs ◽  
Experimental Period ◽  
High Dose ◽  
Herbaceous Plant ◽  
Oral Toxicity ◽  
Toxicity Potential ◽  
Liver And Kidney

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.

scholarly journals Phytochemical Identification, Acute, and Sub-Acute Oral Toxicity Studies of the Foliar Extract of Withania frutescens

Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4528 ◽  
Author(s):  
Abdelfattah EL Moussaoui ◽  
Mohammed Bourhia ◽  
Fatima Zahra Jawhari ◽  
Hamza Mechchate ◽  
Meryem Slighoua ◽  
...  
Keyword(s):  
Acute Toxicity ◽  
Clinical Symptoms ◽  
Ethanolic Extract ◽  
Control Group ◽  
Phytochemical Analysis ◽  
Oral Toxicity ◽  
Phytochemical Composition ◽  
Subacute Toxicity ◽  
Repeated Doses

Withania frutescens (W. frutescens) is a medicinal plant widely used to treat several diseases. This work aims to study phytochemical composition as well as acute and subacute toxicity of W. frutescens hydroethanolic extract in mice. The phytochemical composition of W. frutescens extract was performed using gas chromatographic analysis. Acute toxicity was studied in vivo with oral administration of single doses 400 mg/kg, 1000 mg/kg, and 2000 mg/kg for 14 days. Subacute toxicity was studied with the administration of repeated doses of 400 mg/kg/day and 2000 mg/kg/day for 28 days. Phytochemical analysis of W. frutescens hydro-ethanolic extract confirmed the presence of interesting chemical compounds. Acute toxicity results showed no toxic symptoms in mice treated with an increasing dose up to a maximum of 2000 mg/kg. Alongside acute toxicity, subacute data showed no clinical symptoms nor biochemical or histological alteration in mice treated with an increasing dose up to a maximum of 2000 mg/kg compared to the control group (p < 0.05). This study shows no toxic effects in animals treated with W. frutescens extract, and, therefore, this plant can be considered safe in animals up to 2000 mg/kg under both acute and subacute toxicity conditions.

Safety Evaluation of a Proprietary Food-Grade, Dried Fermentate Preparation of Saccharomyces cerevisiae

2012 ◽  
Vol 31 (1) ◽  
pp. 34-45 ◽  
Author(s):  
Alexander G. Schauss ◽  
R. Glavits ◽  
John Endres ◽  
Gitte S. Jensen ◽  
Amy Clewell
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Clinical Symptoms ◽  
Safety Evaluation ◽  
In Vivo Studies ◽  
Oral Toxicity ◽  
Toxicity Studies ◽  
Adverse Effect Level ◽  
Effect Level

A safety evaluation was performed for EpiCor, a product produced by a proprietary fermentation process using Saccharomyces cerevisiae. Studies included the following assays: bacterial reverse mutation, mouse lymphoma cell mutagenicity, mitogenicity assay in human peripheral lymphocytes, and a cytochrome P450 ([CYP] CYP1A2 and CYP3A4) induction assessment as well as 14-day acute, 90-day subchronic, and 1-year chronic oral toxicity studies in rats. No evidence of genotoxicity or mitogenicity was seen in any of the in vitro or in vivo studies. The CYP assessment showed no interactions or inductions. No toxic clinical symptoms or histopathological lesions were observed in the acute, subchronic, or chronic oral toxicity studies in the rat. Results of the studies performed indicate that EpiCor does not possess genotoxic activity and has a low order of toxicity that is well tolerated when administered orally. The no observable adverse effect level (NOAEL) was 1500 mg/kg body weight (bw)/d for the 90-day study and 800 mg/kg bw/d for the 1 year study, for the highest doses tested.

scholarly journals The utilization of Blaptica dubia cockroaches as an in vivo model to test antibiotic efficacy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Elliot Collins ◽  
Caleb Martin ◽  
Tyler Blomquist ◽  
Katherine Phillips ◽  
Stuart Cantlay ◽  
...  
Keyword(s):  
Lethal Dose ◽  
In Vivo Model ◽  
Infection Model ◽  
Bacterial Strains ◽  
Biologically Relevant ◽  
E Coli ◽  
Lactam Antibiotic ◽  
High Doses ◽  
Antibiotic Efficacy

AbstractInsects are now well recognized as biologically relevant alternative hosts for dozens of mammalian pathogens and they are routinely used in microbial pathogenesis studies. Unfortunately, these models have yet to be incorporated into the drug development pipeline. The purpose of this work was to begin to evaluate the utility of orange spotted (Blaptica dubia) cockroaches in early antibiotic characterization. To determine whether these model hosts could exhibit mortality when infected with bacteria that are pathogenic to humans, we subjected B. dubia roaches to a range of infectious doses of Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, and Acinetobacter baumannii to identify the medial lethal dose. These results showed that lethal disease did not develop following infection of high doses of S. aureus, and A. baumannii. However, cockroaches infected with E. coli and K. pneumoniae succumbed to infection (LD50s of 5.82 × 106 and 2.58 × 106 respectively) suggesting that this model may have limitations based on pathogen specificity. However, because these cockroaches were susceptible to infection from E. coli and K. pneumoniae, we used these bacterial strains for subsequent antibiotic characterization studies. These studies suggested that β-lactam antibiotic persistence and dose was associated with reduction of hemolymph bacterial burden. Moreover, our data indicated that the reduction of bacterial CFU was directly due to the drug activity. Altogether, this work suggests that the orange-spotted cockroach infection model provides an alternative in vivo setting from which antibiotic efficacy can be evaluated.

scholarly journals Chronic In Vivo Effects of Repeated Exposure to Low Oral Doses of Tetrodotoxin: Preliminary Evidence of Nephrotoxicity and Cardiotoxicity

Toxins ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 96 ◽  
Author(s):  
Andrea Boente-Juncal ◽  
Carmen Vale ◽  
Manuel Cifuentes ◽  
Paz Otero ◽  
Mercedes Camiña ◽  
...  
Keyword(s):  
Lethal Dose ◽  
Preliminary Evidence ◽  
Oral Toxicity ◽  
Cardiac Tissues ◽  
Marine Gastropods ◽  
Urine Production ◽  
Effect Level ◽  
In Vivo Effects ◽  
Oral Doses

Tetrodotoxin (TTX) is one of the most potent naturally occurring neurotoxins. InitiallyTTX was associated with human food intoxications in Japan, but nowadays, concerns about thehuman health risks posed by TTX have increased in Europe after the identification of the toxin infish, marine gastropods, and bivalves captured in European waters. Even when TTX monitoring isnot currently performed in Europe, an acute oral no observable effect level (NOAEL) of 75 μg/kghas been recently established but, to date, no studies evaluating the chronic oral toxicity of TTXhave been released, even when EFSA has highlighted the need for them. Thus, in this work, thechronic effects of low oral TTX doses (below the acute lethal dose 50) were evaluated followinginternationally adopted guidelines. The results presented here demonstrate that low oral doses ofTTX have deleterious effects on renal and cardiac tissues. Moreover, alterations in bloodbiochemistry parameters, urine production, and urinalysis data were already detected at the oraldose of 75 μg/kg after the 28 days exposure. Thus, the data presented here constitute an initialapproach for the chronic evaluation of the in vivo toxicity of tetrodotoxin after its ingestion throughcontaminated fishery products.

scholarly journals Assessment of in vivo chronic toxicity of chitosan and its derivates used as oral insulin carriers

2015 ◽  
Vol 4 (2) ◽  
pp. 281-290 ◽  
Author(s):  
Piyasi Mukhopadhyay ◽  
Sourav Bhattacharya ◽  
Arpita Nandy ◽  
Aditi Bhattacharyya ◽  
Roshnara Mishra ◽  
...  
Keyword(s):  
Chronic Toxicity ◽  
Oral Insulin ◽  
Mice Model ◽  
Oral Toxicity

In the present study, the chronic oral toxicity of chitosan derivates was investigated in the mice model.

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