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Efficacy and mechanism of action of ...

Hamed, Saja H.

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Efficacy and mechanism of action of a new tyrosinase inhibitory agent.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Efficacy and mechanism of action of a new tyrosinase inhibitory agent./
Author:	Hamed, Saja H.
Description:	147 p.
Notes:	Source: Dissertation Abstracts International, Volume: 65-08, Section: B, page: 3968.
Contained By:	Dissertation Abstracts International65-08B.
Subject:	Health Sciences, Pharmacy. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3146503
ISBN:	0496043137

Efficacy and mechanism of action of a new tyrosinase inhibitory agent.
Hamed, Saja H.

Efficacy and mechanism of action of a new tyrosinase inhibitory agent. - 147 p.

Source: Dissertation Abstracts International, Volume: 65-08, Section: B, page: 3968.

Thesis (Ph.D.)--University of Cincinnati, 2004.

Acquired hyperpigmentation diseases are common skin diseases. An example is melasma that is permanent in middle-aged women. Hyperpigmentation diseases have psychosocial and cosmetic importance since they are common on sun-exposed areas of the face and the neck. Various treatments are available in the market, but none are completely satisfactory. Most popular skin depigmenting products use a tyrosinase inhibitor as the active ingredient as a result of the key role played by tyrosinase in melanin biosynthesis. The success of these products is limited for two basic reasons: safety or overall effectiveness. Because of the need to provide a skin depigmenting agent that is more efficacious, more stable and less cytotoxic we have analyzed a novel compound, deoxyarbutin (DA). DA was synthesized based on key structure/function relationships of tyrosinase inhibitors, for its tyrosinase inhibition and depigmenting efficacy. DA demonstrated less cytotoxicity, compared to hydroquinone (HQ), in the three normal human skin cell types (i.e., melanocytes, keratinocytes and fibroblasts). This cytotoxicity was not associated with dramatic changes on the morphology of the keratinocytes as in HQ. The lower cytotoxicity of DA as compared to HQ lends support to the stability of DA, lack of auto-oxidation, and the less harmful by-products generated from its metabolism by tyrosinase and/or other metabolic routes. DA was shown in our cell based assay to effectively inhibit tyrosinase activity and melanin synthesis. DA inhibition was reversible whereas HQ showed less or no reversibility. Further, DA reversed skin hyperpigmentation of human skin grafted onto immunocompromised mice with no irritation or negative effect on the graft histology. This lightening effect didn't reach statistical significance and the sample size is small (n = 3). In addition, evidence is provided for the need to standardize the methods used to screen for new tyrosinase inhibitory agents and that MTT assay is not the viability assay of choice when assessing the effect of DA and HQ on cell viability.

ISBN: 0496043137Subjects--Topical Terms:

1017737
Health Sciences, Pharmacy.

Efficacy and mechanism of action of a new tyrosinase inhibitory agent.
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245 1 0 $a Efficacy and mechanism of action of a new tyrosinase inhibitory agent.
300 $a 147 p.
500 $a Source: Dissertation Abstracts International, Volume: 65-08, Section: B, page: 3968.
500 $a Chairman: R. Randall Wickett.
502 $a Thesis (Ph.D.)--University of Cincinnati, 2004.
520 $a Acquired hyperpigmentation diseases are common skin diseases. An example is melasma that is permanent in middle-aged women. Hyperpigmentation diseases have psychosocial and cosmetic importance since they are common on sun-exposed areas of the face and the neck. Various treatments are available in the market, but none are completely satisfactory. Most popular skin depigmenting products use a tyrosinase inhibitor as the active ingredient as a result of the key role played by tyrosinase in melanin biosynthesis. The success of these products is limited for two basic reasons: safety or overall effectiveness. Because of the need to provide a skin depigmenting agent that is more efficacious, more stable and less cytotoxic we have analyzed a novel compound, deoxyarbutin (DA). DA was synthesized based on key structure/function relationships of tyrosinase inhibitors, for its tyrosinase inhibition and depigmenting efficacy. DA demonstrated less cytotoxicity, compared to hydroquinone (HQ), in the three normal human skin cell types (i.e., melanocytes, keratinocytes and fibroblasts). This cytotoxicity was not associated with dramatic changes on the morphology of the keratinocytes as in HQ. The lower cytotoxicity of DA as compared to HQ lends support to the stability of DA, lack of auto-oxidation, and the less harmful by-products generated from its metabolism by tyrosinase and/or other metabolic routes. DA was shown in our cell based assay to effectively inhibit tyrosinase activity and melanin synthesis. DA inhibition was reversible whereas HQ showed less or no reversibility. Further, DA reversed skin hyperpigmentation of human skin grafted onto immunocompromised mice with no irritation or negative effect on the graft histology. This lightening effect didn't reach statistical significance and the sample size is small (n = 3). In addition, evidence is provided for the need to standardize the methods used to screen for new tyrosinase inhibitory agents and that MTT assay is not the viability assay of choice when assessing the effect of DA and HQ on cell viability.
520 $a Based on our viability and in vivo studies, deoxyarbutin has the potential to be a safe and effective depigmenting agent and to be an effective alternative to hydroquinone, the skin depigmenting standard with known safety drawbacks.
590 $a School code: 0045.
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650 4 $a Health Sciences, Pharmacology. $3 1017717
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790 1 0 $a Wickett, R. Randall, $e advisor
790 $a 0045
791 $a Ph.D.
792 $a 2004
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