| id |
ndltd-OhioLink-oai-etd.ohiolink.edu-ucin1158576749
|
| record_format |
oai_dc
|
| spelling |
ndltd-OhioLink-oai-etd.ohiolink.edu-ucin11585767492021-08-03T06:11:26Z EFFECT OF DEOXYARBUTIN AND ITS SECOND-GENERATION DERIVATIVES ON MELANOCYTE VIABILITY AND FUNCTION CHAWLA, SMITA Therapeutic treatment of skin pigmentary disorders such as melasma, solar lentigines, and post inflammatory hyperpigmentation has been challenging and seldom completely successful. The majority of these therapies target tyrosinase, a key enzyme required for pigment synthesis. The lack of success is due to the less than desired efficacy and safety of tyrosinase inhibitors marketed as skin lightening agents (i.e. hydroquinone, kojic acid and arbutin). We propose that the tyrosinase inhibitor deoxyArbutin (dA) and second-generation derivatives of dA, deoxyFuran, thio-dA, and fluoro-dA, have the potential to be effective inhibitors of skin melanization. In this study, we have analyzed the modulating effects of dA and its derivatives on melanocyte function and viability. At safe concentrations, these compounds reversibly down-regulated melanogenesis by competitively inhibiting the key enzyme, tyrosinase. Lineweaver-Burk plot analysis revealed that these compounds had higher competitive inhibitor potencies against tyrosinase as compared to hydroquinone (HQ). Concentrations of these compounds that did compromise viability of melanocytes resulted in an inhibition of cell proliferation (i.e., cytostatic) as opposed to the induction of apoptosis (i.e., cytotoxic) that was induced by HQ. Melanogenic enzymes; tyrosinase and TRP-1 mediated this cytostatic effect of dA and its derivatives. A comparative evaluation of oxidative stress demonstrated that a minimal amount of Reactive Oxygen Species (ROS) was generated upon treatment with dA and derivatives, in contrast to the dramatic amount induced by HQ. This increase in ROS triggered an increase in activity of the endogenous antioxidant catalase in treated melanocytes. Endogenous catalase was sufficient to protect cells against ROS generated by dA and its derivatives, but not HQ, since treatment with exogenous antioxidants conferred protection against HQ, but not dA and derivatives. Thus, dA and second-generation derivatives demonstrate great potential for therapeutic use in hyperpigmentation because they are effective tyrosinase inhibitors and less toxic relative to the current gold standard, HQ. 2006 English text University of Cincinnati / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=ucin1158576749 http://rave.ohiolink.edu/etdc/view?acc_num=ucin1158576749 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
|
| collection |
NDLTD
|
| language |
English
|
| sources |
NDLTD
|
| author |
CHAWLA, SMITA
|
| spellingShingle |
CHAWLA, SMITA
EFFECT OF DEOXYARBUTIN AND ITS SECOND-GENERATION DERIVATIVES ON MELANOCYTE VIABILITY AND FUNCTION
|
| author_facet |
CHAWLA, SMITA
|
| author_sort |
CHAWLA, SMITA
|
| title |
EFFECT OF DEOXYARBUTIN AND ITS SECOND-GENERATION DERIVATIVES ON MELANOCYTE VIABILITY AND FUNCTION
|
| title_short |
EFFECT OF DEOXYARBUTIN AND ITS SECOND-GENERATION DERIVATIVES ON MELANOCYTE VIABILITY AND FUNCTION
|
| title_full |
EFFECT OF DEOXYARBUTIN AND ITS SECOND-GENERATION DERIVATIVES ON MELANOCYTE VIABILITY AND FUNCTION
|
| title_fullStr |
EFFECT OF DEOXYARBUTIN AND ITS SECOND-GENERATION DERIVATIVES ON MELANOCYTE VIABILITY AND FUNCTION
|
| title_full_unstemmed |
EFFECT OF DEOXYARBUTIN AND ITS SECOND-GENERATION DERIVATIVES ON MELANOCYTE VIABILITY AND FUNCTION
|
| title_sort |
effect of deoxyarbutin and its second-generation derivatives on melanocyte viability and function
|
| publisher |
University of Cincinnati / OhioLINK
|
| publishDate |
2006
|
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1158576749
|
| work_keys_str_mv |
AT chawlasmita effectofdeoxyarbutinanditssecondgenerationderivativesonmelanocyteviabilityandfunction
|
| _version_ |
1719432458053615616
|
