A behavioural study of the effect of pentadecapeptide BPC 157 in Parkinson's disease models in mice and gastric lesions induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydrophyridine.
The effect of a stomach pentadecapeptide, BPC 157, on Parkinson's disease in mice was investigated, along with its salutary activity on stomach lesions induced by parkinsongenic agents. Parkinsongenic agents, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (30.0 mg x kg(-1)b.w. i.p. once daily for 6d, and after 4d once 50.0 mg x kg(-1)b.w. i.p.) or reserpine (5.0 mg x kg(-1)b.w. i.p.) were applied i.p. BPC 157 (1.50 microg or 15.0 ng x kg(-1)b.w. i.p.) was applied 15 min before or alternatively 15 min after each MPTP administration. In reserpine studies, BPC 157 (10.0 microg or 10.0 ng x kg(-1)b.w. i.p.) was given either 15 min before reserpine or in the already established complete catalepsy 24 h thereafter. BPC 157 strongly improved the MPTP-impaired somatosensory orientation and reduced the MPTP-induced hyperactivity, and most importantly, MPTP-motor abnormalities (tremor, akinesia, catalepsy -otherwise very prominent in saline control), leading to almost complete abolition of otherwise regularly lethal course of MPTP treatment in controls. Likewise, in reserpine experiments, BPC 157 strongly prevented the development of otherwise very prominent catalepsy and when applied 24 h thereafter reversed the established catalepsy. In addition, a reduction of reserpine-hypothermy (BPC 157 pre-treatment) and reversal of further prominent temperature fall (BPC 157 post-treatment) have been consistently observed. Taking together these data, as the two most suitable animal models were consistently used and since the high effectiveness was demonstrated in pre- and post-treatment, microg and ng regimens, BPC 157 as an organoprotector should be further therapeutically investigated. Additionally, given in either regimen, pentadecapeptide BPC 157 strongly attenuated the stomach lesions in mice that otherwise consistently appeared in mice treated with the parkinsogenic neurotoxin MPTP.
Sikiric
P
P
Department of Pharmacology, Medical Faculty University of Zagreb, Croatia.
Marovic
A
A
Matoz
W
W
Anic
T
T
Buljat
G
G
Mikus
D
D
Stancic-Rokotov
D
D
Separovic
J
J
Seiwerth
S
S
Grabarevic
Z
Z
Rucman
R
R
Petek
M
M
Ziger
T
T
Sebecic
B
B
Zoricic
I
I
Turkovic
B
B
Aralica
G
G
Perovic
D
D
Duplancic
B
B
Lovric-Bencic
M
M
Rotkvic
I
I
Mise
S
S
Jagic
V
V
Hahn
V
V
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001831:Body Temperature / Q000187:drug effects; D002375:Catalepsy / Q000139:chemically induced / Q000517:prevention & control; D007035:Hypothermia / Q000139:chemically induced / Q000503:physiopathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects; D010300:Parkinson Disease / Q000401:mortality / Q000473:pathology* / Q000503:physiopathology; D010446:Peptide Fragments / Q000494:pharmacology*; D011506:Proteins / Q000494:pharmacology*; D012110:Reserpine / Q000494:pharmacology; D013272:Stomach Diseases / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*
D000897:Anti-Ulcer Agents; D010446:Peptide Fragments; D011506:Proteins; D012110:Reserpine; C083833:BPC 157