Melanogenic Inhibition and Toxicity Assessment of Flavokawain A and B on B16/F10 Melanoma Cells and Zebrafish (Danio rerio)

Excessive production of melanin implicates hyperpigmentation disorders. Flavokawain A (FLA) and flavokawain B (FLB) have been reported with anti-melanogenic activity, but their melanogenic inhibition and toxicity effects on the vertebrate model of zebrafish are still unknown. In the present study, cytotoxic as well as melanogenic effects of FLA and FLB on cellular melanin content and tyrosinase activity were evaluated in α-MSH-induced B16/F10 cells. Master regulator of microphthalmia-associated transcription factor (Mitf) and the other downstream melanogenic-related genes were verified via quantitative real time PCR (qPCR). Toxicity assessment and melanogenesis inhibition on zebrafish model was further observed. FLA and FLB significantly reduced the specific cellular melanin content by 4.3-fold and 9.6-fold decrement, respectively in α-MSH-induced B16/F10 cells. Concomitantly, FLA significantly reduced the specific cellular tyrosinase activity by 7-fold whilst FLB by 9-fold. The decrement of melanin production and tyrosinase activity were correlated with the mRNA suppression of Mitf which in turn down-regulate Tyr, Trp-1 and Trp-2. FLA and FLB exhibited non-toxic effects on the zebrafish model at 25 and 6.25 µM, respectively. Further experiments on the zebrafish model demonstrated successful phenotype-based depigmenting activity of FLA and FLB under induced melanogenesis. To sum up, our findings provide an important first key step for both of the chalcone derivatives to be further studied and developed as potent depigmenting agents.

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Toxicity Assessment of 7 Anticancer Compounds in Zebrafish

International Journal of Toxicology ◽

10.1177/1091581814523142 ◽

2014 ◽

Vol 33 (2) ◽

pp. 98-105 ◽

Cited By ~ 15

Author(s):

Xiao-Ping Gao ◽

Feng Feng ◽

Xiao-Qi Zhang ◽

Xiao-Xin Liu ◽

Yu-Bin Wang ◽

...

Keyword(s):

Drug Development ◽

Mycophenolic Acid ◽

Drug Toxicity ◽

Toxicity Assessment ◽

Gambogic Acid ◽

Zebrafish Model ◽

Anticancer Compounds ◽

Pectoral Fins ◽

Pericardial Edema ◽

Vertebrate Model

Toxicity is one of the major reasons for failure in drug development. Zebrafish, as an ideal vertebrate model, could also be used to evaluate drug toxicity. In this study, we aimed to show the predictability and highlight novel findings of toxicity in zebrafish model. Seven anticancer compounds, including triptolide (TP), gambogic acid (GA), mycophenolic acid (MPA), curcumin, auranofin, thalidomide, and taxol, were assessed in zebrafish for their toxicity. Three compounds (GA, TP, and taxol) showed highest acute lethality, with 50% lethal concentration ≈ 1 μmol/L. Missing tails, severe pericardial edema, and enlarged yolk sacs were observed in MPA-treated embryos. The development of pectoral fins was severely disturbed in thalidomide-, GA-, and TP-treated embryos. Bradycardia was observed in MPA- and thalidomide-treated groups. Our findings suggested that the zebrafish are a good model for toxicity assessment of anticancer compounds.

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Zebrafish (Danio rerio) as a Vertebrate Model Host To Study Colonization, Pathogenesis, and Transmission of FoodborneEscherichia coliO157

mSphere ◽

10.1128/mspheredirect.00365-17 ◽

2017 ◽

Vol 2 (5) ◽

Cited By ~ 15

Author(s):

Daniel H. Stones ◽

Alexander G. J. Fehr ◽

Laurel Thompson ◽

Jacqueline Rocha ◽

Nicolas Perez-Soto ◽

...

Keyword(s):

Escherichia Coli ◽

Danio Rerio ◽

Food Chain ◽

Vertebrate Host ◽

Zebrafish Model ◽

Content Type ◽

Vertebrate Model ◽

Waterborne Infection ◽

Enterocyte Effacement ◽

Foodborne Infection

ABSTRACTFoodborne infections with enterohemorrhagicEscherichia coli(EHEC) are a major cause of diarrheal illness in humans and can lead to severe complications such as hemolytic uremic syndrome. Cattle and other ruminants are the main reservoir of EHEC, which enters the food chain through contaminated meat, dairy, or vegetables. Here, we describe the establishment of a vertebrate model for foodborne EHEC infection, using larval zebrafish (Danio rerio) as a host and the protozoan preyParamecium caudatumas a vehicle. We follow pathogen release from the vehicle, intestinal colonization, microbe-host interactions, and microbial gene induction within a live vertebrate host, in real time, throughout the course of infection. We demonstrate that foodborne EHEC colonizes the gastrointestinal tract faster and establishes a higher burden than waterborne infection. Expression of the locus of enterocyte effacement (LEE), a key EHEC virulence factor, was observed early during infection, mainly at sites that experience fluid shear, and required tight control to enable successful host colonization. EHEC infection led to strain- and LEE-dependent mortality in the zebrafish host. Despite the presence of the endogenous microbiota limiting EHEC colonization levels, EHEC colonization and virulence can be studied either under gnotobiotic conditions or against the backdrop of an endogenous (and variable) host microbiota. Finally, we show that the model can be used for investigation of factors affecting shedding and transmission of bacteria to naive hosts. Overall, this constitutes a useful model, which ideally complements the strengths of existing EHEC vertebrate models.IMPORTANCEEnterohemorrhagicEscherichia coli(EHEC) is a foodborne pathogen which can cause diarrhea, vomiting, and, in some cases, severe complications such as kidney failure in humans. Up to 30% of cattle are colonized with EHEC, which can enter the food chain through contaminated meat, dairy, and vegetables. In order to control infections and stop transmission, it is important to understand what factors allow EHEC to colonize its hosts, cause virulence, and aid transmission. Since this cannot be systematically studied in humans, it is important to develop animal models of infection and transmission. We developed a model which allows us to study foodborne infection in zebrafish, a vertebrate host that is transparent and genetically tractable. Our results show that foodborne infection is more efficient than waterborne infection and that the locus of enterocyte effacement is a key virulence determinant in the zebrafish model. It is induced early during infection, and loss of tight LEE regulation leads to a decreased bacterial burden and decreased host mortality. Overall, the zebrafish model allows us to study foodborne infection, including pathogen release from the food vehicle and gene regulation and its context of host-microbe interactions, as well as environmental shedding and transmission to naive hosts.

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Graphene-Like Layers from Carbon Black: In Vivo Toxicity Assessment

Nanomaterials ◽

10.3390/nano10081472 ◽

2020 ◽

Vol 10 (8) ◽

pp. 1472

Author(s):

Marta d’Amora ◽

Michela Alfe ◽

Valentina Gargiulo ◽

Silvia Giordani

Keyword(s):

Danio Rerio ◽

Toxicity Assessment ◽

Biological Parameters ◽

In Vivo Toxicity ◽

Toxicological Profile ◽

Vertebrate Model ◽

Promising Application ◽

Good Biocompatibility ◽

Insight Into

Graphene-like (GL) layers, a new graphene-related material (GRM), possess peculiar chemical, colloidal, optical and transport properties. Considering the very recent promising application of GL layers in biomedical and bioelectronic fields, it is of utmost importance to investigate the toxicological profile of these nanomaterials. This study represents an important first report of a complete in vivo toxicity assessment of GL layers on embryonic zebrafish (Danio rerio). Our results show that GL layers do not lead to any perturbations in the different biological parameters evaluated, indicating their good biocompatibility on a vertebrate model. The new insight into the biosafety of GL layers will expand their applications in nanomedicine.

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Urea-Extracted Sericin is Potentially Better Than Kojic Acid in the Inhibition of Melanogenesis Through Increased ROS Generation

10.21203/rs.3.rs-95384/v1 ◽

2020 ◽

Author(s):

Sarocha Cherdchom ◽

Amornpun Sereemasoun ◽

Pornanong Aramwit

Keyword(s):

Kojic Acid ◽

Therapeutic Potential ◽

Chemical Properties ◽

Extraction Methods ◽

Inhibitory Effect ◽

Biological Properties ◽

Tyrosinase Activity ◽

The Other ◽

Ros Generation ◽

Melanin Content

Abstract Background: Hyperpigmentation is a skin disorder, which is caused by an excess production of melanin. The reduction in melanin content without causing undesirable effects is required for the treatment of hyperpigmentation. Sericin is increasingly used as a hyperpigmentation treatment because of its antityrosinase activity. However, the various methods of sericin extraction have an effect on the composition and biological properties. The purpose of this study was to investigate the antioxidant and anti-melanogenic properties of sericin using different extraction methods including acid, base, heat, and urea extraction. Methods: The chemical properties of extracted sericin were assessed in terms of amino acid components, thermal behavior, and UV-vis absorption. The inhibitory effects of sericin on melanogenesis were explored by determining the melanin content and cellular tyrosinase activity in B16F10 cells.Results: Sericin from urea extraction provided different properties when compared with the other extraction methods. Our results indicate that urea-extracted sericin reduced the melanin content and cellular tyrosinase activity more effectively than the other extraction methods. Interestingly, the potential anti-melanogenic activity was more effective than kojic acid, a depigmenting agent used to treat hyperpigmentation.Conclusions: Our results present the potential inhibitory effect of urea-extracted sericin on melanogenesis. Our results support the therapeutic potential of urea-extracted sericin in the treatment of hyperpigmentation and its complications.

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Toxicity assessment of pyriproxyfen in vertebrate model zebrafish embryos ( Danio rerio ): A multi biomarker study

Aquatic Toxicology ◽

10.1016/j.aquatox.2018.01.010 ◽

2018 ◽

Vol 196 ◽

pp. 132-145 ◽

Cited By ~ 48

Author(s):

Kannan Maharajan ◽

Sellamani Muthulakshmi ◽

Bojan Nataraj ◽

Mathan Ramesh ◽

Krishna Kadirvelu

Keyword(s):

Danio Rerio ◽

Toxicity Assessment ◽

Zebrafish Embryos ◽

Vertebrate Model

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Inhibitory Effects of Cycloheterophyllin on Melanin Synthesis

Molecules ◽

10.3390/molecules26092526 ◽

2021 ◽

Vol 26 (9) ◽

pp. 2526

Author(s):

Joong-Hyun Shim

Keyword(s):

Functional Materials ◽

Tyrosinase Activity ◽

Melanin Synthesis ◽

Activity Assay ◽

Inhibitory Effects ◽

Melanin Production ◽

Messenger Ribonucleic Acid ◽

B16f10 Cells ◽

Cell Line Cell ◽

Tyrosinase Related Protein

This study was performed to clarify the inhibitory effects of cycloheterophyllin on melanin synthesis. In order to elucidate the inhibitory effects of cycloheterophyllin on the B16F10 cell line, cell viability, messenger ribonucleic acid (mRNA) expressions, tyrosinase activity assay, and melanin production assay were measured. The effects of cycloheterophyllin on tyrosinase-related protein 1 (TYRP1)/TYRP2/tyrosinase (TYR)/microphthalmia-associated transcription factor (MITF) mRNA expressions and melanin content were determined. Quantitative real-time RT-PCR showed that cycloheterophyllin decreased the mRNA expression level of TYRP1/TYRP2/TYR/MITF genes and melanin production contents than α-MSH-treated B16F10 cells. The tyrosinase activity assay revealed that cycloheterophyllin decreased the melanin production in the B16F10 cells. These data show that cycloheterophyllin increases the whitening effects in the B16F10 cells; thus, cycloheterophyllin is a potent ingredient for skin whitening. Thus, further research on the mechanism of action of cycloheterophyllin for the development of functional materials should be investigated.

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Toxicological Profile of Plasmonic Nanoparticles in Zebrafish Model

International Journal of Molecular Sciences ◽

10.3390/ijms22126372 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6372

Author(s):

Marta d’Amora ◽

Vittoria Raffa ◽

Francesco De Angelis ◽

Francesco Tantussi

Keyword(s):

Surface Plasmon Resonance ◽

Adverse Effects ◽

Physicochemical Properties ◽

Surface Plasmon ◽

Danio Rerio ◽

Plasmonic Nanoparticles ◽

Comprehensive Understanding ◽

Zebrafish Model ◽

Toxicological Profile ◽

Materials Used

Plasmonic nanoparticles are increasingly employed in several fields, thanks to their unique, promising properties. In particular, these particles exhibit a surface plasmon resonance combined with outstanding absorption and scattering properties. They are also easy to synthesize and functionalize, making them ideal for nanotechnology applications. However, the physicochemical properties of these nanoparticles can make them potentially toxic, even if their bulk metallic forms are almost inert. In this review, we aim to provide a more comprehensive understanding of the potential adverse effects of plasmonic nanoparticles in zebrafish (Danio rerio) during both development and adulthood, focusing our attention on the most common materials used, i.e., gold and silver.

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Biocompatibility and radioprotection by newly characterized melanin pigment and its production from Dietzia schimae NM3 in optimized whey medium by response surface methodology

Annals of Microbiology ◽

10.1186/s13213-021-01628-6 ◽

2021 ◽

Vol 71 (1) ◽

Author(s):

Sahar Eskandari ◽

Zahra Etemadifar

Keyword(s):

Response Surface Methodology ◽

Response Surface ◽

Radical Scavenging Activity ◽

Radical Scavenging ◽

Nutrient Broth ◽

Tyrosinase Activity ◽

Brown Pigment ◽

Scavenging Activity ◽

Protection Factor ◽

Melanin Production

Abstract Purpose To characterize and optimize the productivity of melanin using an extremotolerant actinobacterium, Dietzia schimae NM3, for the first time. Methods An extracellular brown pigment produced by D. schimae NM3 in the nutrient broth and cheese whey medium by adding L-tyrosine. The extracted melanin was analyzed by UV-visible, HPLC, and FTIR assays. The radical scavenging activity (by DPPH) and sun protection factor (SPF) of the extracted melanin were measured. The melanin cytotoxicity was assayed by MTT and chromate biosorption was measured by atomic absorption spectroscopy. Finally, melanin production by D. schimae NM3 was optimized by response surface methodology (RSM) using Box-Behnken design in the whey medium. Result The purified melanin showed similar peak to the standard melanin (SIGMA) at 3.5 min in HPLC, and C=O bands, NH2, CH, C-N, and aromatic groups by FTIR. The radical scavenging activity (by DPPH) and SPF of the extracted melanin were obtained 188.9% and 20.22, respectively. Using MTT assay, the melanin revealed non-toxic effect on the normal human fibroblast (HFB) cell culture. The melanin yield 790 mg l−1, and tyrosinase activity 3400 U ml−1 were obtained in the medium contained whey powder [5% (w v−1)], L-tyrosine 2.5 g l−1, CuSO4 0.013 g l−1, and pH 10.5, incubated at 32 °C for 3 days. The ANOVA results indicated significant P-value, model F-value, and probability, with insignificant lack of fit. After optimization with mono-factors, the nutrient broth came up with melanin yield as 1.2 g l−1 and tyrosinase activity as 4040 U ml−1. Conclusion This is the first report of melanin production by D. schimae NM3 and this natural melanin showed valuable biological properties such as high antioxidant activity and radioprotection (SPF) and the biocompatibility to human cell line.

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