Document Detail


Evaluation of skin sensitization potential of melatonin and nimesulide by murine local lymph node assay.
MedLine Citation:
PMID:  11576826     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Melatonin is a good candidate for transdermal delivery considering its short plasma half life, low molecular weight and a favorable octanol:water partition coefficient. Nimesulide is a nonsteroidal anti-inflammatory agent used orally and rectally for inflammatory disorders. The objective of this study was to investigate the skin sensitization potential of melatonin and nimesulide using the standard murine local lymph node assay (LLNA). Melatonin (0.5, 2.5, 5.0 and 10.0%, w/v) and nimesulide (0.5, 2.5, 5.0 and 10.0%, w/v) dissolved in acetone:olive oil (4:1, AOO) was applied (25 microl) on the dorsal surface of each ear of female CBA/Ca mice for three consecutive days. On the sixth day, [3H]methyl thymidine was administered intravenously and the uptake of [3H]methyl thymidine (dpm) by the draining lymph nodes was determined by established methods. Dinitrochlorobenzene (DNCB, 0.25%, w/v) and para-aminobenzoic acid (PABA, 2.5%, w/v) were used as positive and negative control, respectively. The mean dpm obtained with melatonin and nimesulide treatment at all concentrations were not significantly different (P>0.05) from that of AOO. The stimulation index (SI) values of melatonin and nimesulide at different concentrations were close to 1. The results of the present study using the standard LLNA approved by US Interagency Coordinating Committee in the Validation of Alternative Methods (ICCVAM) indicate that melatonin and nimesulide are not skin sensitizers. However, since LLNA has shown false negatives with many drugs, clinical trials are certainly needed to exclude the possibility of a weak or delayed type skin sensitization reaction. Further studies using modified LLNA procedures (extended exposure, alternative vehicle systems, pre-abrasion, etc.) may be useful in identifying the weak or delayed type skin sensitization reactions.
Authors:
N Kanikkannan; T Jackson; M S Shaik; M Singh
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences     Volume:  14     ISSN:  0928-0987     ISO Abbreviation:  Eur J Pharm Sci     Publication Date:  2001 Oct 
Date Detail:
Created Date:  2001-09-28     Completed Date:  2001-12-11     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9317982     Medline TA:  Eur J Pharm Sci     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  217-20     Citation Subset:  IM    
Affiliation:
Division of Pharmaceutics, College of Pharmacy, Florida A & M University, Tallahassee, FL 32307, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
Cyclooxygenase Inhibitors / pharmacology
Dinitrochlorobenzene / diagnostic use
Dose-Response Relationship, Drug
Lymph Nodes / drug effects
Melatonin / pharmacology*
Mice
Skin / drug effects*,  immunology
Sulfonamides / pharmacology*
Grant Support
ID/Acronym/Agency:
RR 3020/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 0/Cyclooxygenase Inhibitors; 0/Sulfonamides; 51803-78-2/nimesulide; 73-31-4/Melatonin; 97-00-7/Dinitrochlorobenzene

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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