Page 7 - Gastric pentadecapeptide BPC 157

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982 M. Sturesinic c't rrl. I Journul of' Orthopedic Re.~mrc~h (20031 976-983
5500 1 cells responded by sevenfold increase of the 3H-thymi-
* dine incorporation. The effect of HNE is potentiated.
4500 . I Otherwise, in cells not stimulated with TGF-0, HNE
reduced their growth only 10%~. Accordingly, BPC 157
might act, unlike TGF-P (or bFGF, many fold increased
e 3500 . -, - ;I; factor
proliferative response) [3], as a particular growth
2500
interfering with the growth modifying activities of HNE,
I
otherwise known to be dependent of the activity of
1500 -
growth factors [9,22.29,30].
BPC 157 could be efficient also in vivo as a growth-
regulating factor and may alleviate all sequence of the
mentioned events since these processes improved over
--""
COrmOl BPC 157 2 ugh1 TGF beta 10 numl control and/or standard agents values had already been
shown in pentadecapeptide BPC 157 studies [8,12,16,
Fig. 6. Effect of BPC I57 (as 2 pglml final concentration) or TGF-B (at
10 ng/ml final concentration) on the growth of cultured tendocytes in 17,19-21,3 11. Specifically, besides angiogenesis in Sza-
vitro according to the 'H-thymidine incorporation in the presence of bo's angiogenesis model (i.e., synthetic sponge implan-
only 0.1% FCS (median. minimum, maximum (Med/Min/Max) of tation [21]), evidenced are advanced collagen, reticulin
CPMIwell for quadruplicates of samples). Mann-Whitney test and blood vessels formation, increased tensile breaking
('p < 0.01 vs. control or BPC 157).
force (skin incision wounds [ 171, deep partial thickness
skin burns [ 12]), raised bursting pressure (colon-colon
functional, biomechanical, microscopical and clinical anastomoses [3 11). Healing of segmental osteoperiosteal
recovery in rats, peptide stability, presented with gastric bone defect that otherwise does not heal [ 161 is relevant
pentadecapeptide BPC 157 intraperitoneal applications, for an advanced healing in special and complex condi-
ascertaining suitable delivery, favor routine application tions, and possibly, for tendon healing to bone, as the
in future Achilles tendon therapy. initial healing process was similar to fracture healing
Indicatively, pentadecapeptide BPC 157 has an an- [ 1 11. Therefore, the prominent improvement of other-
giogenic effect and modulates NO-synthesis [ 19,2 I], wise failed healing of transected Achilles tendon (i.e.,
while an alike direct evidence is still lacking for other biomechanically and functionally the healthy values
growth factors [19]. Considering essential role of NO in reached) is within the framework of its healing effect.
healing (see i.e., [6]), these may directly affect, rather This may be from an early positive effect identified at a
than normal circumstances, the repair of connective critical one day period, improved by an application 30
tissues (see i.e., [6]), as an ordered multistage process, min after injury, and/or, gradual increase of the ongoing
occurring proliferation and migration of many cell healing process(es) afforded by each of the subsequent
types, collagen synthesis, angiogenesis, production of daily administrations. Note, in rabbit-pseudoarthrosis
granulation tissue. The end result may be subsequent model, the therapy (i.m.) was started not before seven
tendon cells and collagen fibers high organization in an post-injury-day [ 161. Thus, most likely, presenting the
attempt to restore as closely as possible the original activity throughout the healing process, gastric penta-
structure and function of the damaged tendon. This il- decapeptide BPC 157 reaches the treatment aim, to
lustrated in vitro studies. No effect on the growth of induce and then maintain the healing.
cultured cell of its own presents with capability to react Finally, gastric pentadecapeptide BPC 157 efficacy
with mediators of oxidative stress such as NO [19], or seems to be not hampered by conditions presenting in
HNE [9,22,29,30], here, a negative modulator of the tendons such as Achilles. Otherwise, hypocellular, hyp-
growth. As an end product of lipid peroxidation [9,22, ovascular, hyponeural characteristics generally impair
29,301, HNE-effect is consistently opposed in both medication accessibility, and therapeutic efficacy [ 13,181.
combinations: BPC 157 + HNE (HNE growth inhibiting As mentioned, pentadecapeptide BPC 157 given sys-
effect reversed into growth stimulation of cultured temically (i.p. or i.m.) [12,16] had been already shown to
tendocytes) and HNE + BPC 157 (abolished inhibiting aid healing process in alike complex structures. Deep
activity of the aldehyde), both in the presence of serum partial thickness skin burn [12] and non-union model
and serum deprived conditions. Otherwise, we should [ 161 share at least some of tendon characteristics, espe-
assume that HNE is also present in various tissues under cially due to vascular occlusion at the site directly de-
physiological conditions and produced constantly dur- stroyed by the thermal energy [27] or essentially poor
ing the inflammation and healing. Thus, adding BPC vascularization [ 181. Finally, like in deep partial thick-
157 in vitro alone, or with respect to HNE, even before ness skin burns [12], the potential upregulation of the
(BPC 157 + HNE), as well as later (HNE + BPC 157), growth factors, as well as other local factors, acting to
might reflect its positive effect in vivo healing, too, mediate the growth and repair of the tendon may be
an effect different from that of TGF-P. Serum deprived suggested.