PMID- 11576826
OWN - NLM
STAT- MEDLINE
DCOM- 20011211
LR  - 20201208
IS  - 0928-0987 (Print)
IS  - 0928-0987 (Linking)
VI  - 14
IP  - 3
DP  - 2001 Oct
TI  - Evaluation of skin sensitization potential of melatonin and nimesulide by murine 
      local lymph node assay.
PG  - 217-20
AB  - 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.
FAU - Kanikkannan, N
AU  - Kanikkannan N
AD  - Division of Pharmaceutics, College of Pharmacy, Florida A & M University, 
      Tallahassee, FL 32307, USA.
FAU - Jackson, T
AU  - Jackson T
FAU - Shaik, M S
AU  - Shaik MS
FAU - Singh, M
AU  - Singh M
LA  - eng
GR  - RR 3020/RR/NCRR NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Eur J Pharm Sci
JT  - European journal of pharmaceutical sciences : official journal of the European 
      Federation for Pharmaceutical Sciences
JID - 9317982
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Cyclooxygenase Inhibitors)
RN  - 0 (Dinitrochlorobenzene)
RN  - 0 (Sulfonamides)
RN  - JL5DK93RCL (Melatonin)
RN  - V4TKW1454M (nimesulide)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents, Non-Steroidal/*pharmacology
MH  - Cyclooxygenase Inhibitors/pharmacology
MH  - Dinitrochlorobenzene
MH  - Dose-Response Relationship, Drug
MH  - Lymph Nodes/drug effects
MH  - Melatonin/*pharmacology
MH  - Mice
MH  - Skin/*drug effects/immunology
MH  - Sulfonamides/*pharmacology
EDAT- 2001/09/29 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/09/29 10:00
PHST- 2001/09/29 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/09/29 10:00 [entrez]
AID - S0928098701001762 [pii]
AID - 10.1016/s0928-0987(01)00176-2 [doi]
PST - ppublish
SO  - Eur J Pharm Sci. 2001 Oct;14(3):217-20. doi: 10.1016/s0928-0987(01)00176-2.