In vivo stimulation of connective tissue accumulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ in rat experimental wounds

Maquart FX, Bellon G, Chaqour B, et al. · The Journal of Clinical Investigation

At day 29 the 2 mg chambers held 344% of control collagen hydroxyproline, 230% of the total protein, 223% of the dry weight and 208% of the glycosaminoglycan (all P<0.01); DNA content was not significantly altered in that experiment, and the results present no DNA data for the dose series although the abstract lists DNA among the dose-dependent increases. Collagen rose about twice as much as other proteins and the increase held per mg of DNA; the effect was significant from 0.5 mg per injection; dermatan sulfate rose from 53% to 70% of the glycosaminoglycans; type I and III procollagen mRNAs rose from day 3 to 14 with no rise in TGF-β1 mRNA; the type III fraction of collagen was unchanged. GHK without copper and copper chloride alone had no effect, and the control tripeptide EHP raised collagen less (14.62 against 20.27 µmol hydroxyproline per chamber).

Population

Rats with implanted wound chambers

Intervention

GHK-Cu 2 mg in 0.2 ml injected into the chamber every 3 days for two to three weeks; a dose series of 0.2 to 4.0 mg per injection; GHK without copper and copper chloride at equimolar amounts as controls

Comparator

Saline-injected chambers (in the first experiment the other chamber on the same rat; afterwards separate control rats)

Limitations

Dermal wound-chamber model in rats, no joint tissue; small groups of four to ten chambers. Funded by CNRS, the Université de Reims and Procyte Corporation, which supplied the GHK-Cu and employed two of the authors.