Abstract:
Rheumatoid arthritis (RA) is a form of chronic inflammation, a systemic
autoimmune disorder that destroys synovial joints. The cause of RA is still
unknown, and at present and there is no cure. RA is one of the most common types
of chronic inflammatory polyarthritis. It represents a significant health burden with
an approximately 1% prevalence worldwide. It mainly affects women, two times
more than men. Copper complexes were used in the 1940's to 1970's for the
treatment of the inflammation associated with RA. The ligands chosen were
sarcosyl-L-histidyl-L-lysine (Sar-His-Lys), sarcosyl-L-lysyl-L-histidine (Sar-Lys His), sarcosyl-L-histidyl-L-histidine (Sar-His-His), sarcosyl-L-lysyl-L-lysine (Sar Lys-Lys), sarcosyl-L-glycyl-L-histidine (Sar-Gly-His) and sarcosyl-L-leucyl phenylalanine (Sar-Leu-Phe). Our previous studies have shown equilibrium
constants of H+
, Cu(II), Ni(II) and Zn(II) with these tripeptides and the structures of
the complex species were investigated using UV-Vis, ESR and 1H NMR
spectroscopy. An objective of the study was to increase the available pool of copper
in vivo. This was evaluated using a computer model of blood plasma, which
considers competition with endogenous metal ions and ligands. It is particularly
important that the ligands were evaluated using the Evaluation of Constituent
Concentrations in Large Equilibrium (ECCLE) system, an in vivo speciation model
of blood plasma. Dermal absorption is the preferred method of administration, and
so this study used partition coefficients and tissue permeability studies to assess the
bioavailability of the different complexes. Based on the results of this study, Sar Lys-His and Sar-Gly-His have a higher mobilising capacity than all the other
tripeptides.
