Evaluation of the Skin-Sensitizing Potential of Brazilian Green Propolis

Propolis is a resinous mixture produced by bees from their secretions and plant material, so its composition varies depending on its botanical origin. Propolis has several beneficial bioactivities, but its skin sensitization properties have long been suspected. Nevertheless, the skin sensitization potency of Brazilian green propolis (BGP) has not been scientifically evaluated. Here, we used scientifically reliable tests to evaluate it. In vitro antigenicity test based on the human cell line activation test (OECD TG 442E) was performed by measuring the expression of CD54 and CD86, which are indicators of the antigenicity of test substances, on THP-1 and DC2.4 cells. BGP did not affect the expression of either marker on THP-1 cells, but upregulated the expression of CD86 on DC2.4 cells, suggesting that BGP may be a skin sensitizer. Then, we performed local lymph node assay (LLNA, OECD TG 429) as a definitive in vivo test. LLNA showed that 1.70% BGP primed skin sensitization and is a “moderate sensitizer”. Our results indicate scientific proof of the validity of arbitrary concentrations (1–2%), which have been used empirically, and provide the first scientific information on the safe use of BGP.

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Skin sensitization

Human & Experimental Toxicology ◽

10.1177/0960327115601760 ◽

2015 ◽

Vol 34 (12) ◽

pp. 1222-1230 ◽

Cited By ~ 19

Author(s):

DA Basketter ◽

IR White ◽

JP McFadden ◽

I Kimber

Keyword(s):

Safety Evaluation ◽

In Vitro Assays ◽

Skin Sensitization ◽

Human Data ◽

Allergic Skin ◽

Local Lymph Node ◽

Allergic Contact ◽

Risk Managers

Skin sensitization associated with allergic contact dermatitis is a common health problem and is an important consideration for toxicologists in safety assessment. Historically, in vivo predictive tests have been used with good success to identify substances that have the potential to induce skin sensitization, and these tests formed the basis of safety evaluation. These original tests are now being replaced gradually either by in vitro assays or by further refinements of in vivo methods such as the local lymph node assay. Human data have also been available to inform classification decisions for some substances and have been used by risk managers to introduce measures for exposure reduction. However, humans encounter hazards in the context of exposure rather than in the form of intrinsic hazards per se, and so in this article, we have examined critically the extent to which human data have been used to refine classification decisions and safety evaluations. We have also evaluated information on the burden of human allergic skin disease and used this to address the question of whether, and to what extent, the identification and evaluation of skin sensitization hazards has led to an improvement of public and/or occupational health.

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Anti-inflammatory potential of african leaf water extract

Journal of Agriculture and Applied Biology ◽

10.11594/jaab.01.02.02 ◽

2020 ◽

Vol 1 (2) ◽

pp. 46-53

Author(s):

Lusi Agus Setiani ◽

Zaldi Rusli

Keyword(s):

Leaf Extract ◽

Protein Denaturation ◽

Scientific Information ◽

Water Extract ◽

Inflammatory Activity ◽

In Vivo Test ◽

Flavonoid Compounds ◽

Anti Inflammatory

Inflammation is the immune system's main response to infection and irritation. African leaf (Gymnanthemum amygdalinum) is one of the medicinal plants that can be used as anti-inflammatory because of the presence of flavonoid compounds. Flavonoid compounds have an anti-inflammatory effect that can regulate arachidonic acid metabo-lism by inhibiting cyclooxygenase (COX) and lipooksigenase activi-ties. This study aims to obtain scientific information and the potential of African leaf extract as an anti-inflammatory in vitro and in vivo test. In this study, in vitro and in vivo anti-inflammatory activity tests were carried out. The in vitro anti-inflammatory activity was evaluated by the ability of African leaf extracts to prevent protein denaturation and in vivo anti-inflammatory activity by observing the reduction of edema in the soles of rats induced by carrageenan by giving three lev-els of doses of African leaf extract. The results showed that the African leaf extract at a concentration of 8273.91 mg L-1 was able to inhibit 50% denatured protein (IC50), while in the in vivo test African leaf had the potential as an anti-inflammatory with the most effective percent-age of inhibition at a dose of 200 mg kg-1 which is 85.20%. African leaf have the potential of approximately 2 times greater than the positive control of diclofenac sodium which is 45.70%.

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Evaluation of Phototoxic and Skin Sensitization Potentials of PLA2-Free Bee Venom

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2015/157367 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Yunwi Heo ◽

Min-Jung Pyo ◽

Seong Kyeong Bae ◽

Hyunkyoung Lee ◽

Young Chul Kwon ◽

...

Keyword(s):

Neutral Red ◽

Positive Control ◽

Bee Venom ◽

Test Substance ◽

Skin Sensitization ◽

Photo Effect ◽

Major Player ◽

Local Lymph Node

Bee venom (BV) from honey bee (Apis mellifera L.) has been used in oriental medicine and cosmetic ingredients because of its diverse pharmacological activities. In many studies, among BV components, phospholipase A2(PLA2) is known as a major player in BV-induced allergic reaction. Therefore, we removed PLA2from BV using ultrafiltration and then investigatedin vitrophototoxicity andin vivoskin sensitization of PLA2-free BV (PBV) in comparison with regular BV. The 3T3 neutral red uptake phototoxicity assay can be appropriated to identify the phototoxic effect of a test substance upon the exposure of ultraviolet A. Chlorpromazine, a positive control, showed high levels of photoirritation factor and mean photo effect values, while BV and PBV had less of these values. Local lymph node assay is an alternative method to evaluate skin sensitization potential of chemicals. BALB/c mice were treated withp-phenylenediamine (PPD, positive control), BV, or PBV. In all of PPD concentrations, stimulation indexes (SI) as sensitizing potential of chemicals were ≥1.6, determined to be sensitizer, while SI levels of BV and PBV were below 1.6. Thus, based on these findings, we propose that both BV and PBV are nonphototoxic compounds and nonsensitizers.

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The Research of Toxicity and Sensitization Potential of PEGylated Silver and Gold Nanomaterials

Toxics ◽

10.3390/toxics9120355 ◽

2021 ◽

Vol 9 (12) ◽

pp. 355

Author(s):

Dong-Han Lee ◽

Seo-Yoon Choi ◽

Ki-Kyung Jung ◽

Jun-Young Yang ◽

Ja-young Jeong ◽

...

Keyword(s):

Immune Response ◽

The Body ◽

Test Method ◽

In Vitro Test ◽

Skin Sensitization ◽

In Vivo Test ◽

Gold Silver ◽

Original Group

Polyethylene glycol (PEG) is a polymer used for surface modification of important substances in the modern pharmaceutical industry and biopharmaceutical fields. Despite the many benefits of PEGylation, there is also the possibility that the application and exposure of the substance may cause adverse effects in the body, such as an immune response. Therefore, we aimed to evaluate the sensitization responses that could be induced through the intercomparison of nanomaterials of the PEG-coated group with the original group. We selected gold/silver nanomaterials (NMs) for original group and PEGylated silver/gold NMs in this study. First, we measured the physicochemical properties of the four NMs, such as size and zeta potential under various conditions. Additionally, we performed the test of the NM’s sensitization potential using the KeratinoSens™ assay for in vitro test method and the LLNA: 5-bromo-2-deoxyuridine (BrdU)-FCM for in vivo test method. The results showed that PEGylated-NMs did not lead to skin sensitization according to OECD TG 442 (alternative test for skin sensitization). In addition, gold nanomaterial showed that cytotoxicity of PEGylated-AuNMs was lower than AuNMs. These results suggest the possibility that PEG coating does not induce an immune response in the skin tissue and can lower the cytotoxicity of nanomaterials.

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Defibrotide Inhibits Platelet Activation by Cathepsin G Released From Stimulated Polymorphonuclear Leukocytes

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648519 ◽

1992 ◽

Vol 67 (06) ◽

pp. 660-664 ◽

Cited By ~ 17

Author(s):

Virgilio Evangelista ◽

Paola Piccardoni ◽

Giovanni de Gaetano ◽

Chiara Cerletti

Keyword(s):

Platelet Activation ◽

Polymorphonuclear Leukocytes ◽

Direct Interaction ◽

Cathepsin G ◽

In Vivo Test ◽

Cell Functions ◽

Test Models ◽

Antithrombotic Effects

SummaryDefibrotide is a polydeoxyribonucleotide with antithrombotic effects in experimental animal models. Most of the actions of this drug have been observed in in vivo test models but no effects have been reported in in vitro systems. In this paper we demonstrate that defibrotide interferes with polymorphonuclear leukocyte-induced human platelet activation in vitro. This effect was not related to any direct interaction with polymorphonuclear leukocytes or platelets, but was due to the inhibition of cathepsin G, the main biochemical mediator of this cell-cell cooperation. Since cathepsin G not only induces platelet activation but also affects some endothelial cell functions, the anticathepsin G activity of defibrotide could help to explain the antithrombotic effect of this drug.

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Adenosine A2A receptor signaling promotes FoxO associated autophagy in chondrocytes

Scientific Reports ◽

10.1038/s41598-020-80244-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Benjamin Friedman ◽

Carmen Corciulo ◽

Cristina M. Castro ◽

Bruce N. Cronstein

Keyword(s):

Cell Line ◽

Metabolic Stress ◽

Human Cell Line ◽

Adenosine A2a Receptor ◽

Autophagic Flux ◽

A2a Receptor ◽

Adenosine A2a ◽

A2ar Agonist

AbstractAutophagy, a homeostatic pathway upregulated during cellular stress, is decreased in osteoarthritic chondrocytes and this reduction in autophagy is thought to contribute to the development and progression of osteoarthritis (OA). The adenosine A2A receptor (A2AR) is a potent anti-inflammatory receptor and deficiency of this receptor leads to the development of OA in mice. Moreover, treatment using liposomally conjugated adenosine or a specific A2AR agonist improved joint scores significantly in both rats with post-traumatic OA (PTOA) and mice subjected to a high fat diet obesity induced OA. Importantly, A2AR ligation is beneficial for mitochondrial health and metabolism in vitro in primary and the TC28a2 human cell line. An additional set of metabolic, stress-responsive, and homeostatic mediators include the Forkhead box O transcription factors (FoxOs). Data has shown that mouse FoxO knockouts develop early OA with reduced cartilage autophagy, indicating that FoxO-induced homeostasis is important for articular cartilage. Given the apparent similarities between A2AR and FoxO signaling, we tested the hypothesis that A2AR stimulation improves cartilage function through activation of the FoxO proteins leading to increased autophagy in chondrocytes. We analyzed the signaling pathway in the human TC28a2 cell line and corroborated these findings in vivo in a metabolically relevant obesity-induced OA mouse model. We found that A2AR stimulation increases activation and nuclear localization of FoxO1 and FoxO3, promotes an increase in autophagic flux, improves metabolic function in chondrocytes, and reduces markers of apoptosis in vitro and reduced apoptosis by TUNEL assay in vivo. A2AR ligation additionally enhances in vivo activation of FoxO1 and FoxO3 with evidence of enhanced autophagic flux upon injection of the liposome-associated A2AR agonist in a mouse obesity-induced OA model. These findings offer further evidence that A2AR may be an excellent target for promoting chondrocyte and cartilage homeostasis.

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In Vitro and In Vivo Biosafety Analysis of Resorbable Polyglycolic Acid-Polylactic Acid Block Copolymer Composites for Spinal Fixation

Polymers ◽

10.3390/polym13010029 ◽

2020 ◽

Vol 13 (1) ◽

pp. 29

Author(s):

Seung Kyun Yoon ◽

Jin Ho Yang ◽

Hyun Tae Lim ◽

Young-Wook Chang ◽

Muhammad Ayyoob ◽

...

Keyword(s):

Lactic Acid ◽

Animal Experiments ◽

Polymeric Materials ◽

Polyglycolic Acid ◽

Poly Lactic Acid ◽

Skin Sensitization ◽

Spinal Fixation ◽

In Vivo Degradation

Herein, spinal fixation implants were constructed using degradable polymeric materials such as PGA–PLA block copolymers (poly(glycolic acid-b-lactic acid)). These materials were reinforced by blending with HA-g-PLA (hydroxyapatite-graft-poly lactic acid) and PGA fiber before being tested to confirm its biocompatibility via in vitro (MTT assay) and in vivo animal experiments (i.e., skin sensitization, intradermal intracutaneous reaction, and in vivo degradation tests). Every specimen exhibited suitable biocompatibility and biodegradability for use as resorbable spinal fixation materials.

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Comparative Evaluation of In Vitro and In Vivo Assays for the Detection of Avian Infectious Bronchitis Virus as a Contaminant of Live Poultry Vaccines

Alternatives to Laboratory Animals ◽

10.1177/026119299802600508 ◽

1998 ◽

Vol 26 (5) ◽

pp. 629-634

Author(s):

Emiliana Falcone ◽

Edoardo Vignolo ◽

Livia Di Trani ◽

Simona Puzelli ◽

Maria Tollis

Keyword(s):

Infectious Bronchitis Virus ◽

Serological Response ◽

Avian Infectious Bronchitis Virus ◽

Animal Testing ◽

Rt Pcr ◽

Pcr Assay ◽

In Vivo Test ◽

Infectious Bronchitis

A reverse transcriptase polymerase chain reaction (RT-PCR) assay specific for identifying avian infectious bronchitis virus (IBV) in poultry vaccines, and the serological response to IBV induced by the inoculation of chicks with a Newcastle disease vaccine spiked with the Massachusetts strain of IBV, were compared for their ability to detect IBV as a contaminant of avian vaccines. The sensitivity of the IBV-RT-PCR assay provided results which were at least equivalent to the biological effect produced by the inoculation of chicks, allowing this assay to be considered a valid alternative to animal testing in the quality control of avian immunologicals. This procedure can easily be adapted to detect a number of contaminants for which the in vivo test still represents the only available method of detection.

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Experimental Evidence for Therapeutic Potentials of Propolis

Nutrients ◽

10.3390/nu13082528 ◽

2021 ◽

Vol 13 (8) ◽

pp. 2528

Author(s):

Priyanshu Bhargava ◽

Debajit Mahanta ◽

Ashish Kaul ◽

Yoshiyuki Ishida ◽

Keiji Terao ◽

...

Keyword(s):

New Zealand ◽

Experimental Evidence ◽

Antioxidant Properties ◽

Geographic Location ◽

Caffeic Acid Phenethyl Ester ◽

Candidate Drug ◽

Brazilian Propolis ◽

Brazilian Green Propolis

Propolis is produced by honeybees from materials collected from plants they visit. It is a resinous material having mixtures of wax and bee enzymes. Propolis is also known as bee glue and used by bees as a building material in their hives, for blocking holes and cracks, repairing the combs and strengthening their thin borders. It has been extensively used since ancient times for different purposes in traditional human healthcare practices. The quality and composition of propolis depend on its geographic location, climatic zone and local flora. The New Zealand and Brazilian green propolis are the two main kinds that have been extensively studied in recent years. Their bioactive components have been found to possess a variety of therapeutic potentials. It was found that Brazilian green propolis improves the cognitive functions of mild cognitive impairments in patients living at high altitude and protects them from neurodegenerative damage through its antioxidant properties. It possesses artepillin C (ARC) as the key component, also known to possess anticancer potential. The New Zealand propolis contains caffeic acid phenethyl ester (CAPE) as the main bioactive with multiple therapeutic potentials. Our lab performed in vitro and in vivo assays on the extracts prepared from New Zealand and Brazilian propolis and their active ingredients. We provided experimental evidence that these extracts possess anticancer, antistress and hypoxia-modulating activities. Furthermore, their conjugation with γCD proved to be more effective. In the present review, we portray the experimental evidence showing that propolis has the potential to be a candidate drug for different ailments and improve the quality of life.

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