scholarly journals Azelaic Acid Esters as Pluripotent Immunomodulatory Molecules: Nutritional Supplements or Drugs

2021 ◽  
Vol 1 (1) ◽  
pp. 42-53
Author(s):  
Elzbieta Izbicka ◽  
Robert T. Streeper
Keyword(s):  
Azelaic Acid ◽  
Metabolic Activation ◽  
Hepatic Metabolism ◽  
Nutritional Supplement ◽  
Human Saliva ◽  
Bacterial Strains ◽  
Human Primary Hepatocytes ◽  
Acid Esters

Azelaic acid and its esters, the azelates, occur naturally in organisms ranging from plants to humans. We have shown that diethyl azelate (DEA) exhibits a broad range of immunomodulatory activities in vitro and in vivo, and mitigates insulin resistance. To further investigate the therapeutic utility of DEA, we evaluated its mutagenicity in Salmonella typhimurium strains, examined metabolism of DEA in rat, dog, monkey and human primary hepatocytes and in human saliva, determined pharmacokinetics of DEA after an oral dose in rats, and queried its physicochemical properties for drug-like characteristics. DEA was not mutagenic in bacterial strains ± rat liver metabolic activation system S-9. It was chemically unstable in hepatocyte culture medium with a half-life of <1 h and was depleted by the hepatocytes in <5 min, suggesting rapid hepatic metabolism. DEA was also quickly degraded by human saliva in vitro. After an oral administration of DEA to rats, the di- and monoester were undetectable in plasma while the levels of azelaic acid increased over time, reached maximum at <2 h, and declined rapidly thereafter. The observed pharmacological properties of DEA suggest that it has value both as a drug or a nutritional supplement.

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.

scholarly journals Human Saliva-Mediated Hydrolysis of Eugenyl-β-D-Glucoside and Fluorescein-di-β-D-Glucoside in In Vivo and In Vitro Models

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 172
Author(s):  
Mariusz Dziadas ◽  
Adam Junka ◽  
Henryk Jeleń
Keyword(s):  
Oral Cavity ◽  
Control Sample ◽  
Rapid Test ◽  
Human Saliva ◽  
In Vitro Models ◽  
Microbial Hydrolysis ◽  
Amoxicillin Trihydrate ◽  
Potassium Clavulanate

Eugenyl-β-D-glucopyranoside, also referred to as Citrusin C, is a natural glucoside found among others in cloves, basil and cinnamon plants. Eugenol in a form of free aglycone is used in perfumeries, flavourings, essential oils and in medicinal products. Synthetic Citrusin C was incubated with human saliva in several in vitro models together with substrate-specific enzyme and antibiotics (clindamycin, ciprofloxacin, amoxicillin trihydrate and potassium clavulanate). Citrusin C was detected using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Citrusin C was completely degraded only when incubated with substrate-specific A. niger glucosidase E.C 3.2.1.21 (control sample) and when incubated with human saliva (tested sample). The addition of antibiotics to the above-described experimental setting, stopped Citrusin C degradation, indicating microbiologic origin of hydrolysis observed. Our results demonstrate that Citrusin C is subjected to complete degradation by salivary/oral cavity microorganisms. Extrapolation of our results allows to state that in the human oral cavity, virtually all β-D-glucosides would follow this type of hydrolysis. Additionally, a new method was developed for an in vivo rapid test of glucosidase activity in the human mouth on the tongue using fluorescein-di-β-D-glucoside as substrate. The results presented in this study serve as a proof of concept for the hypothesis that microbial hydrolysis path of β-D-glucosides begins immediately in the human mouth and releases the aglycone directly into the gastrointestinal tract.

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.

In vitro and in vivo screening of antagonistic bacterial strains from vineyards to controlBotrytis cinereain grapevine tissues

2016 ◽  
pp. 85-92 ◽  
Author(s):  
R. Haidar ◽  
C. Calvo-Garrido ◽  
J. Roudet ◽  
T. Gautier ◽  
A. Deschamps ◽  
...  
Keyword(s):  
Bacterial Strains ◽  
In Vivo Screening

High Content Analysis of an In Vitro Model for Metabolic Toxicity

2014 ◽  
Vol 19 (10) ◽  
pp. 1402-1408 ◽  
Author(s):  
Stephanie D. Cole ◽  
Janna S. Madren-Whalley ◽  
Albert P. Li ◽  
Russell Dorsey ◽  
Harry Salem
Keyword(s):  
Content Analysis ◽  
High Throughput ◽  
Metabolic Activation ◽  
Hepatic Metabolism ◽  
Cell Types ◽  
Multiple Organ ◽  
Compound Libraries ◽  
High Content Analysis ◽  
Calcein Am

In vitro models that accurately and rapidly assess hepatotoxicity and the effects of hepatic metabolism on nonliver cell types are needed by the U.S. Department of Defense and the pharmaceutical industry to screen compound libraries. Here, we report the first use of high content analysis on the Integrated Discrete Multiple Organ Co-Culture (IdMOC) system, a high-throughput method for such studies. We cultured 3T3-L1 cells in the presence and absence of primary human hepatocytes, and exposed the cultures to 4-aminophenol and cyclophosphamide, model toxicants that are respectively detoxified and activated by the liver. Following staining with calcein-AM, ethidium homodimer-1, and Hoechst 33342, high content analysis of the cultures revealed four cytotoxic endpoints: fluorescence intensities of calcein-AM and ethidium homodimer-1, nuclear area, and cell density. Using these endpoints, we observed that the cytotoxicity of 4-aminophenol in 3T3-L1 cells in co-culture was less than that observed for 3T3-L1 monocultures, consistent with the known detoxification of 4-aminophenol by hepatocytes. Conversely, cyclophosphamide cytotoxicity for 3T3-L1 cells was enhanced by co-culturing with hepatocytes, consistent with the known metabolic activation of this toxicant. The use of IdMOC plates combined with high content analysis is therefore a multi-endpoint, high-throughput capability for measuring the effects of metabolism on toxicity.

scholarly journals In vitro versus in vivo metabolic activation of mutagens.

1973 ◽  
Vol 6 ◽  
pp. 71-82 ◽  
Author(s):  
H V Malling ◽  
C N Frantz
Keyword(s):  
Metabolic Activation

scholarly journals Novel scaffold based graphene oxide doped electrospun iota carrageenan/polyvinyl alcohol for wound healing and pathogen reduction: in-vitro and in-vivo study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Marwa H. Gouda ◽  
Safaa M. Ali ◽  
Sarah Samir Othman ◽  
Samia A. Abd Al-Aziz ◽  
Marwa M. Abu-Serie ◽  
...  
Keyword(s):  
Wound Healing ◽  
Graphene Oxide ◽  
Polyvinyl Alcohol ◽  
Hematological Parameters ◽  
Nutritional Supplement ◽  
Hair Follicles ◽  
Nanofiber Scaffold ◽  
Novel Scaffold

AbstractWound healing is a complicated multicellular process that involves several kinds of cells including macrophages, fibroblasts, endothelial cells, keratinocytes and platelets that are leading to their differentiation towards an anti-inflammatory response for producing several chemokines, cytokine and growth factors. In this study, electrospun nanofiber scaffold named (MNS) is composed of polyvinyl alcohol (PVA)/iota carrageenan (IC) and doped with partially reduced graphene oxide (prGO) that is successfully synthesized for wound healing and skin repair. The fabricated MNS was tested in case of infection and un-infection with E. coli and Staphylococcus and in both of the presence and in the absence of yeast as a natural nutritional supplement. Numerous biochemical parameters including total protein, albumin, urea and LDH, and hematological parameters were evaluated. Results revealed that the MNS was proved to be effective on most of the measured parameters and had exhibited efficient antibacterial inhibition activity. Whereas it can be used as an effective antimicrobial agent in wound healing, however, histopathological findings confirmed that the MNS caused re-epithelialization and the presence of yeast induced hair follicles growth and subsequently it may be used to hide formed head wound scar.

scholarly journals In vitro and in vivo antimicrobial activity of Ulva lactuca Linn. (Green algae) associated endophytic bacterial Strains

2016 ◽  
pp. 138-146 ◽  
Author(s):  
Prasanna Habbu ◽  
Vijayanand Warad ◽  
Rajesh Shastri ◽  
Chetan Savant ◽  
Smita Madagundi ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Green Algae ◽  
Ulva Lactuca ◽  
Bacterial Strains

scholarly journals Dietary Supplement Enriched in Antioxidants and Omega-3 Promotes Glutamine Synthesis in Müller Cells: A Key Process against Oxidative Stress in Retina

Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 3216
Author(s):  
Maryvonne Ardourel ◽  
Chloé Felgerolle ◽  
Arnaud Pâris ◽  
Niyazi Acar ◽  
Khaoula Ramchani Ben Othman ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Müller Cells ◽  
Nutritional Supplement ◽  
Glutamine Metabolism ◽  
Muller Cells ◽  
Omega 3 ◽  
Glutamine Synthesis ◽  
The Impact

To prevent ocular pathologies, new generation of dietary supplements have been commercially available. They consist of nutritional supplement mixing components known to provide antioxidative properties, such as unsaturated fatty acid, resveratrol or flavonoids. However, to date, only one preclinical study has evaluated the impact of a mixture mainly composed of those components (Nutrof Total®) on the retina and demonstrated that in vivo supplementation prevents the retina from structural and functional injuries induced by light. Considering the crucial role played by the glial Müller cells in the retina, particularly to regulate the glutamate cycle to prevent damage in oxidative stress conditions, we questioned the impact of this ocular supplement on the glutamate metabolic cycle. To this end, various molecular aspects associated with the glutamate/glutamine metabolism cycle in Müller cells were investigated on primary Müller cells cultures incubated, or not, with the commercially mix supplement before being subjected, or not, to oxidative conditions. Our results demonstrated that in vitro supplementation provides guidance of the glutamate/glutamine cycle in favor of glutamine synthesis. These results suggest that glutamine synthesis is a crucial cellular process of retinal protection against oxidative damages and could be a key step in the previous in vivo beneficial results provided by the dietary supplementation.

scholarly journals Microbial enzymes induce colitis by reactivating triclosan in the mouse gastrointestinal tract

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Jianan Zhang ◽  
Morgan E. Walker ◽  
Katherine Z. Sanidad ◽  
Hongna Zhang ◽  
Yanshan Liang ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Molecular Mechanisms ◽  
Ex Vivo ◽  
Metabolic Activation ◽  
Consumer Products ◽  
Environmental Chemicals ◽  
Intestinal Microbes ◽  
Targeted Inhibition

AbstractEmerging research supports that triclosan (TCS), an antimicrobial agent found in thousands of consumer products, exacerbates colitis and colitis-associated colorectal tumorigenesis in animal models. While the intestinal toxicities of TCS require the presence of gut microbiota, the molecular mechanisms involved have not been defined. Here we show that intestinal commensal microbes mediate metabolic activation of TCS in the colon and drive its gut toxicology. Using a range of in vitro, ex vivo, and in vivo approaches, we identify specific microbial β-glucuronidase (GUS) enzymes involved and pinpoint molecular motifs required to metabolically activate TCS in the gut. Finally, we show that targeted inhibition of bacterial GUS enzymes abolishes the colitis-promoting effects of TCS, supporting an essential role of specific microbial proteins in TCS toxicity. Together, our results define a mechanism by which intestinal microbes contribute to the metabolic activation and gut toxicity of TCS, and highlight the importance of considering the contributions of the gut microbiota in evaluating the toxic potential of environmental chemicals.

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