IN VITRO AND IN VIVO TOXICITY EVALUATION OF TRAPA BISPINOSA ROXB. STARCH

2021 ◽  
pp. 58-62
Author(s):  
SURADWADEE THUNGMUNGMEE ◽  
NAKUNTWALAI WISIDSRI
Keyword(s):  
Lethal Dose ◽  
Clinical Signs ◽  
Fibroblast Cell ◽  
In Vivo Studies ◽  
Oral Toxicity ◽  
Cosmetic Ingredients ◽  
Nih 3T3 ◽  
Fibroblast Cell Lines

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.

Ultradeformable vesicles: concepts and applications relating to the delivery of skin cosmetics

2021 ◽  
Author(s):  
Andang Miatmoko ◽  
Qurrota Ayunin ◽  
Widji Soeratri
Keyword(s):  
Skin Aging ◽  
Water Soluble ◽  
In Vivo Studies ◽  
Active Ingredients ◽  
Self Confidence ◽  
Skin Delivery ◽  
Cosmetic Ingredients ◽  
Insight Into

Skin aging is a phenomenon resulting in reduced self-confidence, thus becoming a major factor in social determinants of health. The use of active cosmetic ingredients can help prevent skin aging. Transfersomes are well known to be capable of deeply penetrating the dermis. This scoping review provides an insight into transfersomes and their prospective use in anti-aging cosmetics. Numerous reports exist highlighting the successful skin delivery of therapeutic agents such as high-molecular-weight, poorly water soluble and poorly permeable active ingredients by means of transfersomes. Moreover, in vitro and in vivo studies have indicated that transfersomes increase the deposition, penetration and efficacy of active ingredients. However, the use of transfersomes in the delivery of active cosmetic ingredients is limited. Considering their similar physicochemical properties, transfersomes should possess considerable potential as a delivery system for anti-aging cosmetics.

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.

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 Establishment and characterization of equine fibroblast cell lines transformed in vivo and in vitro by BPV-1: Model systems for equine sarcoids

Virology ◽  
2008 ◽  
Vol 373 (2) ◽  
pp. 352-361 ◽  
Author(s):  
Z.Q. Yuan ◽  
E.A. Gault ◽  
P. Gobeil ◽  
C. Nixon ◽  
M.S. Campo ◽  
...  
Keyword(s):  
Cell Lines ◽  
Fibroblast Cell ◽  
Model Systems ◽  
Fibroblast Cell Lines

New Benzodioxole-based Pyrazoline Derivatives: Synthesis and Anticandidal, In silico ADME, Molecular Docking Studies

2018 ◽  
Vol 16 (1) ◽  
pp. 82-92 ◽  
Author(s):  
Ahmet Özdemir ◽  
Belgin Sever ◽  
Mehlika Dilek Altıntop
Keyword(s):  
In Silico ◽  
Fungal Infections ◽  
Computational Study ◽  
Docking Studies ◽  
In Vivo Studies ◽  
Heme Group ◽  
In Silico Studies ◽  
Nih 3T3

Background: Azoles are commonly used in the treatment and prevention of fungal infections. They suppress fungal growth by acting on the heme group of lanosterol 14α-demethylase enzyme (CYP51), thus blocking the biosynthesis of ergosterol. </P><P> Objectives: Due to the importance of pyrazolines in the field of antifungal drug design, we aimed to design and synthesize new pyrazoline-based anticandidal agents. Methods: New pyrazoline derivatives were synthesized via the reaction of 1-(chloroacetyl)-3-(2- thienyl)-5-(1,3-benzodioxol-5-yl)-2-pyrazoline with aryl thiols. These compounds were evaluated for their in vitro antifungal effects on Candida species. Docking studies were performed to predict the affinity of the most effective anticandidal agents to substrate binding site of CYP51. Furthermore, MTT assay was performed to determine the cytotoxic effects of the compounds on NIH/3T3 mouse embryonic fibroblast cell line. A computational study for the prediction of ADME properties of all compounds was also carried out. Results: Compounds 5, 8, 10 and 12 were found as the most potent anticandidal agents against Candida albicans and Candida glabrata in this series with the same MIC values of ketoconazole and they also exhibited low toxicity against NIH/3T3 cells. Docking results indicated that all these compounds showed good binding affinity into the active site of CYP51. In particular, chloro substituted compounds 8 and 12 bind to CYP51 through direct coordination with the heme group. According to in silico studies, compound 8 only violated one parameter of Lipinski’s rule of five, making it a potential orally bioavailable agent. Conclusion: Compound 8 was defined as a promising candidate for further in vitro and in vivo studies.

Species differences in the reactivation of organophosphate-inhibited plasma esterases by diacetymonoxime

1976 ◽  
Vol 54 (2) ◽  
pp. 86-92 ◽  
Author(s):  
D. J. Ecobichon
Keyword(s):  
Guinea Pig ◽  
Species Differences ◽  
Marked Effect ◽  
Lethal Dose ◽  
Rat Plasma ◽  
In Vivo Studies ◽  
Rapid Rate ◽  
Plasma Enzymes

A study was conducted to assess whether the protection afforded to organophosphate-poisoned animals by diacetylmonoxime (DAM) was correlated with the reactivation of non-essential aliesterases (AliE). In vitro, the DAM-catalyzed reactivation of plasma AliE and cholinesterases (ΨChE) of rat, rabbit and guinea pig inhibited by 10−5 M diisopropylphosphorofluoridate (DFP) and O,O-dimethyl-2,2-dichlorovinyl phosphate (DDVP) was investigated. Marked reactivation of the rat plasma enzymes was achieved with 10 mM DAM. Higher concentrations (30 mM) were necessary for the slow reactivation of rabbit and guinea pig plasma AliE. Reactivation of the ΨChE of these species was comparatively slow. Reactivation of DDVP-inhibited esterases proceeded in all species at a more rapid rate than those inhibited by DFP. The dependence of ΨChE reactivation upon concomitant more rapid reactivation of AliE by DAM was demonstrated using Sephadex fractionated AliE and ΨChE but only a marked effect was observed with the rat, suggesting that the plasma AliE of this species is functionally different.The in vitro observations were confirmed by in vivo studies in rats and rabbits. DAM (50 or 150 mg/kg), administered to atropinized rats 15 min before a lethal dose of DFP, protected the animals. Few severe toxic signs were observed and reactivation of both plasma AliE and ΨChE occurred. In contrast, DAM protected the rabbit against a lethal dose of DFP but only reactivation of the erythrocyte acetylcholinesterase was observed.

scholarly journals Micropatterned Fibrous Scaffold Produced by Using Template-Assisted Electrospinning Technique for Wound Healing Application

Polymers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 2821
Author(s):  
Norul Ashikin Norzain ◽  
Zhi-Wei Yu ◽  
Wei-Chih Lin ◽  
Hsing-Hao Su
Keyword(s):  
Wound Healing ◽  
Fibroblast Cell ◽  
In Vivo Studies ◽  
Triangular Prism ◽  
Cell Orientation ◽  
Electrospinning Technique ◽  
Fibrous Scaffold ◽  
Combination Technique

This paper describes the fabrication of a structural scaffold consisting of both randomly oriented nanofibers and triangular prism patterns on the scaffold surface using a combination technique of electrospinning and collector templates. The polycaprolactone (PCL) nanofibers were electrospun over a triangular prism pattern mold, which acted as a template. The deposited scaffold was removed from the template to produce a standalone structural scaffold of three-dimensional micropatterned nanofibers. The fabricated structural scaffold was compared with flat randomly oriented nanofibers based on in vitro and in vivo studies. The in vitro study indicated that the structural scaffold demonstrated higher fibroblast cell proliferation, cell elongation with a 13.48 ± 2.73 aspect ratio and 70% fibroblast cell orientation compared with flat random nanofibers. Among the treatment groups, the structural scaffold escalated the wound closure to 92.17% on day 14. Histological staining of the healed wound area demonstrated that the structural scaffold exhibited advanced epithelization of the epidermal layer accompanied by mild inflammation. The proliferated fibroblast cells and collagen fibers in the structural scaffold appeared denser and arranged more horizontally. These results determined the potential of micropatterned scaffolds for stimulating cell behavior and their application for wound healing.

scholarly journals Safety Assessment of Acer tegmentosum Maxim. Water Extract: General Toxicity Studies in Sprague–Dawley Rats and Beagle Dogs With Re-evaluation of Genotoxic Potentials

2021 ◽  
Vol 12 ◽  
Author(s):  
Jin-Sung Park ◽  
Euna Kwon ◽  
Yun-Soon Kim ◽  
Sang-Moo Kim ◽  
Dae-Sun Kim ◽  
...  
Keyword(s):  
Acute Toxicity ◽  
Clinical Signs ◽  
Water Extract ◽  
Deciduous Tree ◽  
Human Consumption ◽  
Beagle Dogs ◽  
Sprague Dawley ◽  
Oral Toxicity

Acer tegmentosum Maxim., commonly known as Manchurian stripe maple, is a deciduous tree belonging to the family of Aceraceae and has been traditionally used in folk medicine for its remedial effects in liver diseases and traumatic bleedings. With a growing body of experimental evidence for its pharmacological efficacies, such as neuroprotective, hepatoprotective, antioxidant, and anti-inflammatory activities, A. tegmentosum has gradually gained popularity as a health supplement and functional food. However, the large part of essential toxicity information still remained lacking despite the possibility of mutagenic potentials as previously suggested, posing safety concerns for human consumption. In this study, we evaluated 90-day repeated oral toxicity of A. tegmentosum Maxim. water extract (ATWE) in SD rats with acute toxicity assessment in beagle dogs, and reevaluated genotoxicity using a combination of in vitro and in vivo assays. During the oral study period, ATWE did not cause toxicity-related clinical signs and mortality in rodents without adverse effects observed in the analysis of hematology, serum biochemistry, and histopathology, establishing &gt;5,000 mg/kg BW as the NOAEL. In addition, doses up to 5,000 mg/kg BW did not cause acute toxicity in beagle dogs. When assessed for genotoxicity using bacterial reverse mutation, chromosome aberration, and micronucleus formation, ATWE showed lack of mutagenicity and clastogenicity. These results demonstrated that AWTE was safe in the present preclinical study for systemic toxicity and genotoxicity at the tested doses, providing a guideline for safe use in humans.

scholarly journals Antibacterial Activity and Pharmacokinetic Profile of a Promising Antibacterial Agent: 22-(2-Amino-phenylsulfanyl)-22-Deoxypleuromutilin

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 878 ◽  
Author(s):  
Xiangyi Zuo ◽  
Xi Fang ◽  
Zhaosheng Zhang ◽  
Zhen Jin ◽  
Gaolei Xi ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Antibacterial Agent ◽  
Lethal Dose ◽  
Intraperitoneal Administration ◽  
Serum Levels ◽  
Pharmacokinetic Profile ◽  
Oral Route ◽  
Oral Toxicity

A new pleuromutilin derivative, 22-(2-amino-phenylsulfanyl)-22-deoxypleuromutilin (amphenmulin), has been synthesized and proved excellent in vitro and in vivo efficacy than that of tiamulin against methicillin-resistant Staphylococcus aureus (MRSA), suggesting this compound may lead to a promising antibacterial agent to treat MRSA infections. In this study, the effectiveness and safety of amphenmulin were further investigated. Amphenmulin showed excellent antibacterial activity against MRSA (minimal inhibitory concentration = 0.0156~8 µg/mL) and performed time-dependent growth inhibition and a concentration-dependent postantibiotic effect (PAE). Acute oral toxicity test in mice showed that amphenmulin was a practical non-toxic drug and possessed high security as a new drug with the 50% lethal dose (LD50) above 5000 mg/kg. The pharmacokinetic properties of amphenmulin were then measured. After intravenous administration, the elimination half-life (T1/2), total body clearance (Clβ), and area under curve to infinite time (AUC0→∞) were 1.92 ± 0.28 h, 0.82 ± 0.09 L/h/kg, and 12.23 ± 1.35 μg·h/mL, respectively. After intraperitoneal administration, the T1/2, Clβ/F and AUC0→∞ were 2.64 ± 0.72 h, 4.08 ± 1.14 L/h/kg, and 2.52 ± 0.81 μg·h/mL, respectively, while for the oral route were 2.91 ± 0.81 h, 6.31 ± 2.26 L/h/kg, 1.67 ± 0.66 μg·h/mL, respectively. Furthermore, we evaluated the antimicrobial activity of amphenmulin in an experimental model of MRSA wound infection. Amphenmulin enhanced wound closure and promoted the healing of wound, which inhibited MRSA bacterial counts in the wound and decreased serum levels of the pro-inflammatory cytokines TNF-α, IL-6, and MCP-1.

Murine monoclonal antibodies against murine uPA receptor produced in gene-deficient mice: Inhibitory effects on receptormediated uPA activity in vitro and in vivo

2007 ◽  
Vol 97 (06) ◽  
pp. 1013-1022 ◽  
Author(s):  
Jesper Pass ◽  
Annika Jögi ◽  
Ida Lund ◽  
Birgitte Rønø ◽  
Morten Rasch ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Lethal Dose ◽  
In Vivo Studies ◽  
Plasminogen Activation ◽  
Amino Terminal ◽  
Anthrax Toxins ◽  
Murine Monoclonal Antibodies ◽  
Deficient Mice

SummaryBinding of urokinase plasminogen activator (uPA) to its cellular receptor, uPAR, potentiates plasminogen activation and localizes it to the cell surface. Focal plasminogen activation is involved in both normal and pathological tissue remodeling processes including cancer invasion. The interaction between uPA and uPAR therefore represents a potential target for anti-invasive cancer therapy. Inhibitors of the human uPA-uPAR interaction have no effect in the murine system. To enable in-vivo studies in murine cancer models we have now generated murine monoclonal antibodies (mAbs) against murine uPAR (muPAR) by immunizing uPAR-deficient mice with recombinant muPAR and screened for antibodies, which inhibit the muPA-muPAR interaction. Two of the twelve mAbs obtained, mR1 and mR2, interfered with the interaction between muPAR and the amino-terminal fragment of muPA (mATF) when analyzed by surface plasmon resonance. The epitope for mR1 is located on domain I of muPAR, while that of mR2 is on domains (II-III). In cell binding experiments using radiolabelled mATF, the maximal inhibition obtained with mR1 was 85% while that obtained with mR2 was 50%. The IC50 value for mR1 was 0.67 nM compared to 0.14 nM for mATF. In an assay based on modified anthrax toxins, requiring cell-bound muPA activity for its cytotoxity, a ~50% rescue of the cells could be obtained by addition of mR1. Importantly, in-vivo efficacy of mR1 was demonstrated by the ability of mR1 to rescue mice treated with a lethal dose of uPA-activatable anthrax toxins.

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