Introduction
While laser therapy is extensively used in wound healing and tissue repair, and promotes the production of various healing growth factors (e.g., vascular endothelial growth factor) [1], it also impairs specific parts of the healing process [2], [3], [4], to which there is as yet no satisfactory solution. Recent evidence [5], [6], [7], [8] suggests that a stable gastric pentadecapeptide BPC 157 (PL-10, PLD-116, PL-14736; Pliva, Croatia), which shows promise and an absence of toxicity in clinical trials for the treatment of inflammatory bowel disease [9], and in the promotion of healing in ulcers and wounds (e.g., [5], [6], [7], [8], [10], [11], [12], [13], [14], [15]), might also be useful in healing laser lesions. In particular, having remarkable stability [16], pentadecapeptide BPC 157, unlike other growth-factor peptides [17], [18], consistently improved burn healing in mice (both microscopically and as measured by tensiometry), when given systemically or locally, and when applied alone, without carrier, counteracted the impairment of burn healing induced by systemic corticosteroids [5], [6]. It also had other effects on corticosteroid-challenged animals. In post-burn stress gastric lesions, BPC 157 had an anti-ulcer effect of its own in non-corticosteroid treated mice and potentiated the anti-ulcer effect observed in mice treated with 6α-methylprednisolone. Pentadecapeptide BPC 157 also inhibited corticosteroid immunosuppression in vitro: splenic cells from burned animals treated with 6α-methylprednisolone had lower reactivity to mitogen than those of control, healthy animals, but the use of BPC 157 (1 μg/g cream) returned this reactivity to control values [5]. These findings led us to study the effect of topical applications of pentadecapeptide BPC 157 on CO2 laser injuries in mice.
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Section snippets
Drugs
Pentadecapeptide BPC157 (GEPPPGKPADDAGLV; mol. wt. 1419) (manufactured by Diagen, d.o.o., Ljubljana, Slovenia) is a partial sequence of the human gastric juice protein BPC. It is freely soluble in water at pH 7.0 and in saline. It was prepared as described before [5], [6], [7], [8], [10], [11], [12], [13], [14], [15]. Peptide with 99% purity (1-des-Gly peptide as impurity) (as measured by high-performance liquid chromatography) dissolved in saline [5], [6], [7], [8], [9], [10], [11], [12], [13]
Results
A consistent injury was induced in all mice subjected to laser, but this was modified dose-dependently if they had been treated with pentadecapeptide BPC 157 cream (Table 1, Table 2, Table 3). Mice injured and then either untreated or treated with vehicle only showed no difference in any respect (i.e., the same poor re-epithelisation ratio was found in both groups). The macroscopic finding in controls of a deep wound crater, with a large area both of necrosis and wound, correlated with the
Discussion
The apparently beneficial effects of pentadecapeptide BPC 157 on the healing of various injuries [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], including deep burns and impairment by systemic corticosteroids in burned animals [5], [6], might be specifically related to impaired healing conditions. Full-thickness burn injury results in a continuous deterioration of blood flow due to vascular sludging, thrombosis formation and oedema, which in turn lead to irreversible ischaemia and
Conclusion
In extending previous studies on burned mice [5], [6], we found that the gastric pentadecapeptide BPC 157 is a safe agent, and that, similar to its reversal of the deleterious effects of corticosteroids on healing, it improves the healing of a CO2 laser injury. This effect is achieved with a simple method of application, and with the peptide stability and efficacy previously indicated (cream containing 1 μg (dissolved in saline)/g neutral cream), with no carrier or protease inhibitor. Obviously,
Acknowledgement
This study was sponsored by Ministry of Science, Republic of Croatia.
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