Synthesis, crystal structures, in vitro anticancer, and in vivo acute oral toxicity studies of bis-imidazolium/benzimidazolium salts and respective dinuclear Ag(I)-N-heterocyclic carbene complexes

2013 ◽  
Vol 66 (18) ◽  
pp. 3211-3228 ◽  
Author(s):  
Rosenani A. Haque ◽  
Noorhafizah Hasanudin ◽  
Muhammad Adnan Iqbal ◽  
Ashfaq Ahmad ◽  
Suzana Hashim ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Acute Oral Toxicity ◽  
Oral Toxicity ◽  
Carbene Complexes ◽  
Toxicity Studies ◽  
Benzimidazolium Salts

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 Anti-malarial activity and toxicity of Aspidosperma nitidum Benth: a plant used in traditional medicine in the Brazilian Amazon

2020 ◽  
Vol 9 (10) ◽  
pp. e5059108817
Author(s):  
Dayse Lucia do Nascimento Brandão ◽  
Michel Tavares Martins ◽  
Adreanne Oliveira Silva ◽  
Amanda Dias Almeida ◽  
Renata Cristina de Paula ◽  
...  
Keyword(s):  
Ethanol Extract ◽  
Neutral Fraction ◽  
Antiplasmodial Activity ◽  
Major Constituent ◽  
Acute Oral Toxicity ◽  
Oral Toxicity ◽  
Alkaloid Fraction ◽  
Low Cytotoxicity

The objective of this work was to evaluate the antiplasmodial activity and toxicity of the extract and fractions obtained from the bark of Aspidosperma nitidum. The ethanol extract obtained from the powdered bark of plants was acid-base partitioned and phytochemically analyzed. The antiplasmodial activity, in vivo antimalarial activity and in vitro cytotoxicity were acessed. The selectivity index (SI) was calculated. The acute oral toxicity and pathological effects, of the ethanol extract was evaluated in mice. The major constituent of the ethanol extract was suggestive of a β-carboline chromophore. The alkaloid and neutral fractions contained compounds with an aspidospermine core as the major constituent. The ethanol extract (IC50 = 3.60 µg/mL), neutral fraction (IC50 = 3.34 µg/mL) and alkaloid fraction (IC50= 2.32 µg/mL) showed high activity against P. falciparum (W2 strain). The ethanol extract and the alkaloid fraction reduced 80% of the parasitemia of P. berghei (ANKA)-infected mice (dose of 500 mg/kg) in the 5th day, which was not sustainable at the 8th day. A similar result was obtained for chloroquine. The ethanol extract (CC50 = 410.65 µg/mL; SI = 114.07), neutral fraction (CC50 = 452.53 µg/mL; SI = 135.49), and alkaloid fraction (CC50 =346.73 µg/mL; SI 149.45) demonstrated low cytotoxicity and high SI. The ethanol extract (5000 mg/kg; gavage) presented low acute oral toxicity, with no clinical or anatomopathological modifications being observed (in comparison to the control group). In vitro studies with a chloroquine-resistant clone of P. falciparum confirmed the antiplasmodial activity of the A. nitidum ethanol extract, and its fractions had low cytotoxicity for HepG2 cells. In vivo studies with P. berghei–infected mice and acute toxicity studies corroborated these results.

scholarly journals Acute, subacute oral toxicity and Ames test of Py-mulin: an antibacterial drug candidate

2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Yuan Fan ◽  
Yunxing Fu ◽  
Yuhang Zhou ◽  
Yu Liu ◽  
Baocheng Hao ◽  
...  
Keyword(s):  
Ames Test ◽  
Clinical Chemistry ◽  
Toxicity Study ◽  
Female Rats ◽  
Drug Candidate ◽  
Antibacterial Drug ◽  
Acute Oral Toxicity ◽  
Oral Toxicity

Abstract Background Py-mulin is a new pleuromutilin derivative with potent antibacterial activities in vitro and in vivo, suggesting this compound may lead to a promising antibacterial drug after further development. The present study is aimed to evaluate the acute and subacute oral toxicity, and the genotoxicity with the standard Ames test according to standard protocols. Methods Acute oral toxicity of Py-mulin was determined using Kunming mice. The 28-day repeated dose oral toxicity study in SD rats was performed according to OECD guideline No. 407. The bacterial reverse mutation (Ames test) was carried out using four Salmonella typhimurium (S. typhimurium) strains TA97, TA98, TA100 and TA1535 with and without S9 metabolic activation. Results The LD50 values in acute oral toxicity were 2973 mg/kg (female mice) and 3891 mg/kg (male mice) calculated by the Bliss method. In subacute toxicity study, 50 mg/kg Py-mulin did not induce any abnormality in body weight, food consumption, clinical sign, hematology, clinical chemistry, organ weight, and histopathology in all of the treatment groups. However, high doses of Py-mulin (100 and 300 mg/kg) displayed slightly hepatotoxicity to female rats. Furthermore, Py-mulin did not significantly increase the number of revertant colonies of four standard S. typhimurium strains with the doses of 0.16–1000 μg/plate in the Ames study. Conclusions Based on our findings, our study provides some information for the safety profile of Py-mulin.

scholarly journals Acute, Multiple-Dose Dermal and Genetic Toxicity of Nu-3: A Novel Antimicrobial Agent

2010 ◽  
Vol 2010 ◽  
pp. 1-8
Author(s):  
Juan Sun ◽  
Yanxin Hu ◽  
Shanping Cao ◽  
Guozhong Zhang ◽  
Lun-Quan Sun ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Multiple Dose ◽  
Hematological Parameters ◽  
Acute Oral Toxicity ◽  
Antimicrobial Compound ◽  
Oral Toxicity ◽  
Genetic Toxicity ◽  
Toxicological Profile

Nu-3 [butyl-phosphate--thymidine--phosphate-butyl] is a modified nucleotide that has been shown to have antimicrobial activity against a range of bacteria includingPseudomonas aeruginosa. However, data on the toxicological profile of Nu-3 are still lacking. In the present study, the toxicity of Nu-3 was evaluated by the following studies: acute oral toxicity, dermal and mucous membrane irritation, multiple-dose toxicity and genotoxicity in vivo and vitro. The acute oral toxicity test in mice showed that Nu-3 had an of 2001mg/kg body weight. The irritation tests on rats revealed that Nu-3 was not irritant, with an irritation scoring of 0. The multiple-dose toxicity study in rats showed that Nu-3 did not cause significant changes in histology, selected serum chemistry, and hematological parameters compared to the controls. Rats administrated with multiple-doses of Nu-3 showed no visible toxic symptoms. Both in vitro and in vivo, Nu-3 exhibited no notable genetic toxicity. Overall, the data suggest that Nu-3 is hypotoxic or nontoxic antimicrobial compound that warrants being further developed for treatingPseudomonas aeruginosainfection.

scholarly journals In vivo and in vitro safety evaluation of fermented Citrus sunki peel extract: acute and 90-day repeated oral toxicity studies with genotoxicity assessment

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jin-Sung Park ◽  
Eun-Young Cho ◽  
Yun-Soon Kim ◽  
Euna Kwon ◽  
Kang-Min Han ◽  
...  
Keyword(s):  
Model Systems ◽  
Toxicity Tests ◽  
Therapeutic Effects ◽  
Oral Toxicity ◽  
Potential Health ◽  
Genetic Toxicity ◽  
Toxicity Studies ◽  
Peel Extract

Abstract Background Citrus sunki Hort. ex Tanaka peel has been traditionally used as an ingredient in folk medicine due to its therapeutic effects on promotion of splenic health and diuresis as well as relief of gastrointestinal symptoms. Although a growing interest in health-promoting natural products and the development of highly concentrated products have facilitated consumption of C. sunki peel, its safety assessment has not been explored, posing a potential health risk. In this study, we carried out a series of systemic and genetic toxicity tests on fermented C. sunki peel extract (FCPE) to provide the essential information required for safe use in human. Methods We conducted acute and 90-day repeated oral toxicity studies in Sprague-Dawley rats to evaluate systemic toxicity, and three genotoxicity assays to measure bacterial mutation reversion, cellular chromosome aberration and in vivo micronucleus formation. Results Single oral administration of FCPE did not cause any clinical signs and lethality in all animals, establishing LD50 to be over 2000 mg/kg BW. Repeated administration of up to 2000 mg/kg BW FCPE for 90 days revealed no test substance-related toxicity as demonstrated in analysis of body weight gain, food/water intake, blood, serum biochemistry, organ weight and histopathology, collectively determining that the no-observable-adverse-effect-level of FCPE is over 2000 mg/kg BW. In addition, we detected no mutagenicity and clastogenicity in FCPE at 5000 μg/plate for the in vitro assays and 2000 mg/kg BW for the in vivo micronucleus test. Conclusion FCPE did not cause systemic and genetic toxicity in our model systems at the tested dose levels. These results suggest a guideline for safe consumption of C. sunki peel in human.

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