Gastric pentadecapeptide BPC 157 accelerates healing of transected rat Achilles tendon and in vitro stimulates tendocytes growth.
In studies intended to improve healing of transected Achilles tendon, effective was a stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, M.W. 1419). Currently in clinical trials for inflammatory bowel disease (PLD-116, PL 14736, Pliva), it ameliorates internal and external wound healing. In rats, the right Achilles tendon transected (5 mm proximal to its calcaneal insertion) presents with a large tendon defect between cut ends. Agents (/kg b.w., i.p., once time daily) (BPC 157 (dissolved in saline, with no carrier addition) (10 microg, 10 ng or 10 pg) or saline (5.0 ml)), were firstly applied at 30 min after surgery, the last application at 24 h before autopsy. Achilles functional index (AFI) was assessed once time daily. Biomechanical, microscopical and macroscopical assessment was on day 1, 4, 7, 10 and 14. Controls generally have severely compromised healing. In comparison, pentadecapeptide BPC 157 fully improves recovery: (i) biomechanically, increased load of failure, load of failure per area and Young's modulus of elasticity; (ii) functionally, significantly higher AFI-values; (iii) microscopically, more mononuclears and less granulocytes, superior formation of fibroblasts, reticulin and collagen; (iv) macroscopically, smaller size and depth of tendon defect, and subsequently the reestablishment of full tendon integrity. Likewise, unlike TGF-beta, pentadecapeptide BPC 157, presenting with no effect on the growth of cultured cell of its own, consistently opposed 4-hydroxynonenal (HNE), a negative modulator of the growth. HNE-effect is opposed in both combinations: BPC 157+HNE (HNE growth inhibiting effect reversed into growth stimulation of cultured tendocytes) and HNE+BPC 157(abolished inhibiting activity of the aldehyde), both in the presence of serum and serum deprived conditions. In conclusion, these findings, particularly, Achilles tendon transection fully recovered in rats, peptide stability suitable delivery, usefully favor gastric pentadecapeptide BPC 157 in future Achilles tendon therapy.
Staresinic
M
M
Department of Pharmacology, Medical Faculty, University of Zagreb, Salata 11, Post Box 916, 10000 Zagreb, Croatia.
Sebecic
B
B
Patrlj
L
L
Jadrijevic
S
S
Suknaic
S
S
Perovic
D
D
Aralica
G
G
Zarkovic
N
N
Borovic
S
S
Srdjak
M
M
Hajdarevic
K
K
Kopljar
M
M
Batelja
L
L
Boban-Blagaic
A
A
Turcic
I
I
Anic
T
T
Seiwerth
S
S
Sikiric
P
P
D000125:Achilles Tendon / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D000447:Aldehydes / Q000494:pharmacology; D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004548:Elasticity / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D011506:Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013314:Stress, Mechanical; D013708:Tendon Injuries / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D013718:Tensile Strength / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053773:Transforming Growth Factor beta1; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
D000447:Aldehydes; D000897:Anti-Ulcer Agents; D004338:Drug Combinations; D010446:Peptide Fragments; D011506:Proteins; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C083833:BPC 157; C027576:4-hydroxy-2-nonenal