Esophagocutaneous
fistulas are a failure of the NO-system, due to
NO-synthase blockage by the NOS-blocker
L-NAME consequently counteracted by
l-arginine and gastric pentadecapeptide
BPC 157 (
l-arginine <
BPC 157), precipitating a therapeutic benefit. Previously, there was an established BPC 157-NO-system interaction.
BPC 157 GEPPPGKPADDAGLV, MW 1419 (LD1 not achieved), is a safe and stable anti-
ulcer peptide, successful in
inflammatory bowel disease trials, counteracting
esophagitis, sphincter failure, gastrointestinal and
skin ulcers, gastrocutaneous or colocutaneous
fistulas. We treated rats with established cervical esophagocutaneous
fistulas throughout four days (both open skin and esophageal defects, with significant leakage) with
BPC 157 (parenterally and perorally) and
L-NAME (blocking NO genesis) and
l-arginine (NO-substrate) alone or in combination. RT-PCR investigated eNOS, iNOS, COX-2
mRNA levels in the
fistulas. We evidenced a closely inter-related process of unhealed skin, esophageal defects, unhealed
fistulas (up regulated eNOS, iNOS and COX2
mRNA levels), usually lethal, particularly NO-system related and
therapy dependent. Generally, the course of
fistula healing was accelerated either to a greater extent (with
BPC 157 (in particular, less eNOS gene expression) completely counteracting
L-NAME effects, in L-NAME+BPC 157 and L-NAME+l-arginine+BPC 157 groups), or to a lesser extent (with
l-arginine). Conversely, the process was aggravated, rapidly and prominently (with
L-NAME). In particular,
BPC 157 was effective either given per-orally/intraperitoneally, in μg- and ng-regimens. Shortly, defects started to heal, with less
fistula leakage and no mortality at day 4. Failure of pyloric and lower esophageal sphincter pressure was restored, with practically no
esophagitis.