scholarly journals Safety Evaluation of Multiple Strains ofLactobacillus plantarumandPediococcus pentosaceusin Wistar Rats Based on the Ames Test and a 28-Day Feeding Study

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Cheng-Chih Tsai ◽  
Sew-Fen Leu ◽  
Quan-Rong Huang ◽  
Lan-Chun Chou ◽  
Chun-Chih Huang
Keyword(s):  
Wistar Rats ◽  
Clinical Chemistry ◽  
Toxicity Study ◽  
Bacterial Strains ◽  
Oral Toxicity ◽  
Short Term ◽  
Mutagenic Potential ◽  
Multiple Strains

Three lactic acid bacterial strains,Lactobacillus plantarum, HK006, and HK109, andPediococcus pentosaceusPP31 exhibit probiotic potential as antiallergy agents, both in vitro and in vivo. However, the safety of these new strains requires evaluation when isolated from infant faeces or pickled cabbage. Multiple strains (HK006, HK109, and PP31) were subject to a bacterial reverse mutation assay and a short-term oral toxicity study. The powder product exhibited mutagenic potential inSalmonellaTyphimurium strains TA98 and TA1535 (with or without metabolic activation). In the short-term oral toxicity study, rats received a normal dosage of 390 mg/kg/d (approximately9×109 CFU/kg/d) or a high dosage of 1950 mg/kg/d (approximately4.5×1010 CFU/kg/d) for 28 d. No adverse effects were observed regarding the general condition, behaviour, growth, feed and water consumption, haematology, clinical chemistry indices, organ weights, or histopathologic analysis of the rats. These studies have demonstrated that the consumption of multiple bacterial strains is not associated with any signs of mutagenicity ofS.Typhimurium or toxicity in Wistar rats, even after consuming large quantities of bacteria.

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 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 Safety evaluation of fructooligosaccharide (FOSSENCETM): Acute, 14-day, and subchronic oral toxicity study in Wistar rats

2018 ◽  
Vol 2 ◽  
pp. 239784731878775 ◽  
Author(s):  
Manish Jain ◽  
Manoj Gote ◽  
Ashok Kumar Dubey ◽  
S Narayanan ◽  
H. Krishnappa ◽  
...  
Keyword(s):  
Body Weight ◽  
Wistar Rats ◽  
Clinical Chemistry ◽  
Clinical Signs ◽  
Safety Evaluation ◽  
Toxicity Study ◽  
Feed Consumption ◽  
Oral Toxicity ◽  
Trophic Effect ◽  
Neurological Effects

Fructooligosaccharide (FOS) has been used in infant formula and conventional foods as prebiotics. Short chain FOS (FOSSENCETM) is produced by a patented process of biotransformation of sucrose by the action of enzyme from live microbial cells, hence toxicology studies were initiated to assess its safety. The objective of the present study was to determine safety of FOSSENCETM in acute, 14-day, and subchronic (90-day) toxicity studies. In acute and 14-day studies, administration of the FOSSENCETM to Wistar rats did not cause any mortality or clinical signs and changes in body weights, feed consumption, and gross pathology at the doses of 2000, 5000, and 9000 mg/kg body weight. In the subchronic (90-day) toxicity study, FOSSENCETM was administered by oral gavage to Wistar rats at the doses of 0, 2000, 5000, and 9000 mg/kg/day for 90 days. No treatment-related clinical signs or mortalities were observed. Similarly, no treatment-related toxicologically or biologically significant changes in body weight, feed consumption, ophthalmological findings, neurological effects, hematology, clinical chemistry, urinalysis, and gross pathological findings were noticed. However, statistically significant increase in weight of cecum (without correlative microscopic change) was noted at all the test item-treated groups in males and females and was considered to be a trophic effect and not a toxic effect in rats.

scholarly journals Synthesis and Characterization of Carboxymethyl Chitosan Nanosponges with Cyclodextrin Blends for Drug Solubility Improvement

Gels ◽  
2022 ◽  
Vol 8 (1) ◽  
pp. 55
Author(s):  
Syeda Sadia Batool Rizvi ◽  
Naveed Akhtar ◽  
Muhammad Usman Minhas ◽  
Arshad Mahmood ◽  
Kifayat Ullah Khan
Keyword(s):  
Oral Delivery ◽  
Drug Loading ◽  
Toxicity Study ◽  
In Vitro Dissolution ◽  
Preparation Technique ◽  
Oral Toxicity ◽  
Sem Images ◽  
Enhanced Solubility

This study aimed to enhance the solubility and release characteristics of docetaxel by synthesizing highly porous and stimuli responsive nanosponges, a nano-version of hydrogels with the additional qualities of both hydrogels and nano-systems. Nanosponges were prepared by the free radical polymerization technique and characterized by their solubilization efficiency, swelling studies, sol-gel studies, percentage entrapment efficiency, drug loading, FTIR, PXRD, TGA, DSC, SEM, zeta sizer and in vitro dissolution studies. In vivo toxicity study was conducted to assess the safety of the oral administration of prepared nanosponges. FTIR, TGA and DSC studies confirmed the successful grafting of components into the stable nano-polymeric network. A porous and sponge-like structure was visualized through SEM images. The particle size of the optimized formulation was observed in the range of 195 ± 3 nm. The fabricated nanosponges noticeably enhanced the drug loading and solubilization efficiency of docetaxel in aqueous media. The drug release of fabricated nanosponges was significantly higher at pH 6.8 as compared to pH 1.2 and 4.5. An acute oral toxicity study endorsed the safety of the system. Due to an efficient preparation technique, as well as its enhanced solubility, excellent physicochemical properties, improved dissolution and non-toxic nature, nanosponges could be an efficient and a promising approach for the oral delivery of poorly soluble drugs.

In-vitro and in-vivo evaluation of antidiabetic activity of Withania coagulans extract

2019 ◽  
Vol 09 ◽  
Author(s):  
Tejas Patel ◽  
B.N. Suhagia
Keyword(s):  
Blood Glucose ◽  
Acute Toxicity ◽  
Aqueous Extract ◽  
Pancreatic Beta Cell ◽  
Toxicity Study ◽  
Acute Toxicity Study ◽  
Withania Coagulans ◽  
Study Results

Background: Diabetes mellitus is major issue to public health as its prevalence is rising day by day. Synthetic agents available for the diabetic treatment are expensive or produce undesirable side effect on chronic use and some of them are not suitable during pregnancy. Herbal medicines accepted widely due to side effects and low cost. Objective: The aim of present study was to evaluate the activity of Withania coagulans extract using In-vitro and In-vivo model. Methods: Different three types of Withania coagulans extract were prepared using aqueous (W1), Alcohol (W2) and hydro-alcoholic (50:50) mixture (W3). In-vitro Anti-diabetic activity of the all three extracts evaluated using RINm5F Pancreatic beta cells.Further, n-vivo anti-diabetic evaluation performed by administering 50 mg/kg (p.o) aqueous extract for 7 days in Streptozotocin (STZ)-induced mice. Body weight of the animals was also determined to perform acute toxicity study. Results: The results of in –vitro cell based study indicated that among all three extract, aqueous extract (W1) of Withania coagulans showed potential increase in inulin release. The EC50 of the W1 (249.6 µg/L) which is compared with standard (Glibenclamide) EC50. From the results of In-vitro study, W1 subjected for acute toxicity study and the acute toxicity study results indicated LD50 of 50mg/kg. Diabetic rats treated with W1 extract at oral dose of 50 mg/kg for 7 days showed 34.17% reduction in blood glucose in comparison to untreated diabetic (STZ-induced) rats. Blood glucose levels of Standard treated (Glibenclamide) and control untreated. Conclusion: In conclusion, results of pancreatic beta cell based study showed increase in insulin release by administration of extract. Further aqueous extract (W1) was potentially reduced blood glucose level in STZ induced diabetic mice.

scholarly journals Improved in vivo PET imaging of the adenosine A2A receptor in the brain using [18F]FLUDA, a deuterated radiotracer with high metabolic stability

2021 ◽  
Author(s):  
Thu Hang Lai ◽  
Magali Toussaint ◽  
Rodrigo Teodoro ◽  
Sladjana Dukić-Stefanović ◽  
Daniel Gündel ◽  
...  
Keyword(s):  
Specific Binding ◽  
Radiochemical Yield ◽  
Toxicity Study ◽  
In Vivo Evaluation ◽  
One Pot ◽  
Specific Binding Ratio ◽  
Mri Studies ◽  
The Brain

Abstract Purpose The adenosine A2A receptor has emerged as a therapeutic target for multiple diseases, and thus the non-invasive imaging of the expression or occupancy of the A2A receptor has potential to contribute to diagnosis and drug development. We aimed at the development of a metabolically stable A2A receptor radiotracer and report herein the preclinical evaluation of [18F]FLUDA, a deuterated isotopologue of [18F]FESCH. Methods [18F]FLUDA was synthesized by a two-step one-pot approach and evaluated in vitro by autoradiographic studies as well as in vivo by metabolism and dynamic PET/MRI studies in mice and piglets under baseline and blocking conditions. A single-dose toxicity study was performed in rats. Results [18F]FLUDA was obtained with a radiochemical yield of 19% and molar activities of 72–180 GBq/μmol. Autoradiography proved A2A receptor–specific accumulation of [18F]FLUDA in the striatum of a mouse and pig brain. In vivo evaluation in mice revealed improved stability of [18F]FLUDA compared to that of [18F]FESCH, resulting in the absence of brain-penetrant radiometabolites. Furthermore, the radiometabolites detected in piglets are expected to have a low tendency for brain penetration. PET/MRI studies confirmed high specific binding of [18F]FLUDA towards striatal A2A receptor with a maximum specific-to-non-specific binding ratio in mice of 8.3. The toxicity study revealed no adverse effects of FLUDA up to 30 μg/kg, ~ 4000-fold the dose applied in human PET studies using [18F]FLUDA. Conclusions The new radiotracer [18F]FLUDA is suitable to detect the availability of the A2A receptor in the brain with high target specificity. It is regarded ready for human application.

scholarly journals Synthesis, characterization, and pharmacological evaluation of thiourea derivatives

2020 ◽  
Vol 18 (1) ◽  
pp. 764-777
Author(s):  
Sumaira Naz ◽  
Muhammad Zahoor ◽  
Muhammad Naveed Umar ◽  
Saad Alghamdi ◽  
Muhammad Umar Khayam Sahibzada ◽  
...  
Keyword(s):  
Spectroscopic Techniques ◽  
Organosulfur Compounds ◽  
Bacterial Strains ◽  
Thiourea Derivatives ◽  
Toxicological Effects ◽  
Pharmaceutical Industries ◽  
Uv Visible ◽  
Hematological And Biochemical Parameters

AbstractThioureas and their derivatives are organosulfur compounds having applications in numerous fields such as organic synthesis and pharmaceutical industries. Symmetric thiourea derivatives were synthesized by the reaction of various anilines with CS2. The synthesized compounds were characterized using the UV-visible and nuclear magnetic resonance (NMR) spectroscopic techniques. The compounds were screened for in vitro inhibition of α-amylase, α-glucosidase, acetylcholinesterase (AChE), and butyrylcholinesterase (BuChE) enzymes and for their antibacterial and antioxidant potentials. These compounds were fed to Swiss male albino mice to evaluate their toxicological effects and potential to inhibit glucose-6-phosphatase (G6Pase) inhibition. The antibacterial studies revealed that compound 4 was more active against the selected bacterial strains. Compound 1 was more active against 2,2-diphenyl-1-picrylhydrazyl and 2,2’-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radicals, AChE, BuChE, and α-glucosidase. Compound 2 was more potent against α-amylase and G6Pase. Toxicity studies showed that compound 4 is safe as it exerted no toxic effect on any of the hematological and biochemical parameters or on liver histology of the experimental animals at any studied dose rate. The synthesized compounds showed promising antibacterial and antioxidant potential and were very active (both in vitro and in vivo) against G6Pase and moderately active against the other selected enzymes used in this study.

Case study in 21 st century ecotoxicology: using in vitro aromatase inhibition data to predict short term in vivo responses in adult female fish

2020 ◽  
Author(s):  
Daniel L. Villeneuve ◽  
Brett R. Blackwell ◽  
Jenna E. Cavallin ◽  
Wan‐Yun Cheng ◽  
David J. Feifarek ◽  
...  
Keyword(s):  
Adult Female ◽  
Female Fish ◽  
Aromatase Inhibition ◽  
Short Term ◽  
Inhibition Data

Safety Assessment of a Hydroethanolic Extract of Caralluma fimbriata

2013 ◽  
Vol 32 (5) ◽  
pp. 385-394 ◽  
Author(s):  
Antoinette Y. Odendaal ◽  
Narendra S. Deshmukh ◽  
Tennille K. Marx ◽  
Alexander G. Schauss ◽  
John R. Endres ◽  
...  
Keyword(s):  
Developmental Toxicity ◽  
Toxicity Study ◽  
Developmental Study ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Toxicological Assessment ◽  
Sprague Dawley Rats ◽  
Chromosomal Aberration Test ◽  
Hydroethanolic Extract

This toxicological assessment evaluated the safety of a hydroethanolic extract prepared from Caralluma fimbriata (CFE), a dietary supplement marketed worldwide as an appetite suppressant. Studies included 2 in vitro genotoxicity assays, a repeated dose oral toxicity study, and a developmental study in rats. No evidence of in vitro mutagenicity or clastogenicity surfaced in the in vitro studies at concentrations up to 5000 μg of extract/plate (Ames test) or 5000 μg of extract/mL (chromosomal aberration test). No deaths or treatment-related toxicity were seen in the 6-month chronic oral toxicity study in Sprague-Dawley rats conducted at 3 doses (100, 300, and 1000 mg/kg body weight (bw)/d). The no observed effect level for CFE in this study was considered to be 1000 mg/kg bw/d. A prenatal developmental toxicity study conducted at 3 doses (250, 500, and 1000 mg/kg bw/d) in female Sprague-Dawley rats resulted in no treatment-related external, visceral, or skeletal fetal abnormalities, and no treatment-related maternal or pregnancy alterations were seen at and up to the maximum dose tested. CFE was not associated with any toxicity or adverse events.

scholarly journals Mutagenicity evaluation of Anastatica hierochuntica L. aqueous extract in vitro and in vivo

2017 ◽  
Vol 243 (4) ◽  
pp. 375-385 ◽  
Author(s):  
Siti Rosmani Md Zin ◽  
Zahurin Mohamed ◽  
Mohammed A Alshawsh ◽  
Won F Wong ◽  
Normadiah M Kassim
Keyword(s):  
Aqueous Extract ◽  
Positive Control ◽  
In Vitro Assay ◽  
In Vivo Study ◽  
Sufficient Evidence ◽  
Aqueous Extracts ◽  
Mutagenic Potential ◽  
Vitro Assay

Anastatica hierochuntica L. ( A. hierochuntica), a folk medicinal plant, was evaluated for mutagenic potential via in vitro and in vivo assays. The in vitro assay was conducted according to modified Ames test, while the in vivo study was performed according to Organisation for Economic Co-operation and Development guideline for mammalian erythrocyte micronucleus assay. Four groups ( n= 5 males and 5 females per group) Sprague Dawley rats were randomly chosen as the negative control, positive control (received a single intramuscular injection of cyclophosphamide 50 mg/kg), 1000 and, 2000 mg/kg A. hierochuntica aqueous extracts. All groups except the positive control were treated orally for three days. Findings of the in vitro assay showed mutagenic potential of AHAE at 0.04 and 0.2 mg/ml. However, no mutagenic effect was demonstrated in the in vivo study up to 2000 mg/kg. No significant reduction in the polychromatic and normochromatic erythrocytes ratio was noted in any of the groups. Meanwhile, high micronucleated polychromatic erythrocytes frequency was seen in cyclophosphamide-treated group only. These findings could perhaps be due to insufficient dosage of A. hierochuntica aqueous extracts to cause genetic damage on the bone marrow target cells. Further acute and chronic in vivo toxicity studies may be required to draw pertinent conclusion on the safety aspect of A. hierochuntica aqueous extracts consumption. Impact statement In this paper, we report on the mutagenicity evaluation of Anastatica hierochuntica aqueous extract. This is a significant research in view of the popularity of this herb consumption by the people across the globe despite of limited scientific evidence on its toxicity potential. This study is intended to encourage more extensive related research in order to provide sufficient evidence and guidance for determining its safe dosage.

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