Pentadecapeptide BPC 157 cream improves burn-wound healing and attenuates burn-gastric lesions in mice.
The effects of the gastric pentadecapeptide BPC 157 were investigated when administered topically or systemically in burned mice. This agent is known to have a beneficial effect in a variety of models of gastrointestinal lesions, as well as on wound or fracture healing. Deep partial skin thickness burns (1.5x1.5 cm) covering 20% of total body area, were induced under anesthesia on the back of mice by controlled burning and gastric lesions were assessed 1, 2, 3, 7, 14 and 21 days following injury. The first application of BPC 157 was immediately following burning, and thereafter, once daily, until 24 h before sacrifice. In the initial experiments, exposure to direct flame for 5 s, the BPC 157 was applied at 10 microg or 10 ng/kg b.w. intraperitoneally (i.p.) by injection or alternatively, topically, at the burn, as a thin layer of cream (50 microg of BPC 157 dissolved in 2 ml of distilled water was mixed with 50 g of commercial neutral cream (also used as local vehicle-control)), while silver sulfadiazine 1% cream was a standard agent acting locally. Others received no local medication: they were treated i.p. by injection of distilled water (distilled water-control) or left without any medication (control). In subsequent experiments involving deeper burns (direct flame for 7 s), BPC 157 creams (50 microg, 5 microg, 500 ng, 50 ng or 5 ng of BPC 157 dissolved in 2 ml of distilled water was mixed with 50 g of commercial neutral cream), or vehicle as a thin layer of cream, were applied topically, at the burn. Compared with untreated controls, in both experiments, in the BPC 157 cream-treated mice all parameters of burn healing were improved throughout the experiment: less edema was observed and inflammatory cell numbers decreased. Less necrosis was seen with an increased number of capillaries along with an advanced formation of dermal reticulin and collagen fibers. An increased number of preserved follicles were observed. Two weeks after injury, BPC 157 cream-treated mice completely reversed the otherwise poor re-epithelization ratio noted in the untreated control or mice treated with vehicle only. Tensiometry investigation showed an increased breaking strength and relative elongation of burned skin, while water content in burned skin decreased. This was, however, not the case with the vehicle or silver sulfadiazine. Relative to the control values, in silver sulfadiazine cream-treated mice, only collagen fiber formation was increased, in addition to a decreased inflammatory cell number. Relative to control values, BPC 157 given i.p. decreased the number of inflammatory cells, lowered water content in burned skin, and raised breaking strength and relative elongation of burned skin during tensiometry. Through the experimental period, gastric lesions were continuously noted in all thermally injured mice left without local medication and they were consistently attenuated only by BPC 157 treatments: either given i.p. (at either dose), or given locally (at either concentration). Other treatments (i.e. local treatment with silver sulfadiazine cream or neutral cream in mice subjected for 5 s to direct flame), led to only poor, if any attenuation. This stable gastric pentadecapeptide appears to be active and gives a stimulation to burn healing at the defect site. The agent may act by causing an upregulation of the growth factors, as well as influencing other local factors.
Mikus
D
D
Department of Pharmacology, Medical Faculty, University of Zagreb, Salata 11, P.O. Box 916, 10000, Zagreb, Croatia.
Sikiric
P
P
Seiwerth
S
S
Petricevic
A
A
Aralica
G
G
Druzijancic
N
N
Rucman
R
R
Petek
M
M
Pigac
B
B
Perovic
D
D
Kolombo
M
M
Kokic
N
N
Mikus
S
S
Duplancic
B
B
Fattorini
I
I
Turkovic
B
B
Rotkvic
I
I
Mise
S
S
Prkacin
I
I
Konjevoda
P
P
Stambuk
N
N
Anic
T
T
D000287:Administration, Topical; D000704:Analysis of Variance; D000818:Animals; D002056:Burns / Q000188:drug therapy*; D004195:Disease Models, Animal; D005753:Gastric Mucosa / Q000187:drug effects*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009824:Ointments; D010446:Peptide Fragments / Q000494:pharmacology*; D011336:Probability; D011506:Proteins / Q000494:pharmacology*; D011897:Random Allocation; D012720:Severity of Illness Index; D013272:Stomach Diseases / Q000209:etiology* / Q000473:pathology*; D016896:Treatment Outcome; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology
D009824:Ointments; D010446:Peptide Fragments; D011506:Proteins; C083833:BPC 157