RESUMEN
AIM: To study anxiolytic effect of a gastric pentadecapeptide, BPC-157. METHODS: In shock probe/burying test, pentadecapeptide BPC-157 (10 microg/kg, 10 ng/kg, ip), diazepam (0.075, 0.0375 mg/kg, ip), and an equivolume of saline (5 mL/kg, ip) were given at 30 min prior test. In light/dark test, the same dosage of diazepam, BPC-157, and saline were given at 45 min prior procedure. RESULTS: Shock probe/burying test: rats treated with either diazepam or pentadecapeptide BPC-157 were much less afraid after the shock: almost not burying and the total time spent in burying was clearly less than in controls. However, while in the diazepam treated rats the number of shocks received increased over control values, in pentadecapeptide BPC-157 treated groups the number of shocks remained not modified compared with the control values. Light/dark test: after exposure to the intense light, diazepam treated mice had longer latencies of crossing to the dark compartment, a greater number of crossing and a greater number of exploratory rearing, and spent longer time in the light compartment, as compared to the control mice, while BPC-157 mice had a similar behavior to that of the control mice. In contrast with the effect in light area, in dark zone diazepam produced no change with respect to controls, while BPC-157 (10 microg/kg) mice had a greater number of crossing and a greater number of exploratory rearing. CONCLUSION: Both diazepam and BPC-157 displayed a bidirectional effect, but the activity of pentadecapeptide BPC-157 was particular, and different from diazepam.
Asunto(s)
Ansiolíticos/farmacología , Ansiedad , Conducta Animal/efectos de los fármacos , Fragmentos de Péptidos/farmacología , Proteínas/farmacología , Animales , Oscuridad , Diazepam/farmacología , Luz , Masculino , Ratones , Distribución Aleatoria , Ratas , Ratas WistarRESUMEN
Hemorrhagic mucosal lesions in the stomach in the rat induced by an intragastrical application of 1 ml of 50 or 75% ethanol were aggravated by preceding lung damage provoked by an intratracheal instillation of pyrogen-free saline or HCl (pH 1.75) or 50-h exposure to 100% oxygen. Due to the particular preceding aggravating circumstances, these lesions were taken to be of a special kind, rather than ordinary. So far, it is not known whether and how antiulcer agents may influence these lesions. Rats received an intratracheal (i.t.) HCl instillation [1.5 ml/kg HCl (pH 1.75)] (lung-lesion), and an intragastric instillation of 96% ethanol (gastric lesion; 1 ml/rat, 24 h after i.t. HCl instillation), and were sacrificed 1 h after ethanol. Basically, in lung injured rats, the subsequent ethanol-gastric lesion was markedly aggravated. This aggravation, however, in turn, did not affect the severity of the lung lesions in the further period, at least for a 1-h observation. Taking intratracheal HCl-instillation as time 0, a gastric pentadecapeptide, GEPPPGKPADDAGLV, M.W.1419, coded BPC 157 (PL-10, PLD-116; 10 microg, 10 ng, 10 pg), ranitidine (10 mg), atropine (10 mg), omeprazole (10 mg), were given [/kg, intraperitoneally (i.p.)] (1) once, only prophylactically [as a pre-treatment (at -1 h), or as a co-treatment (at 0)], or only therapeutically (at +18 h or +24 h); (2) repeatedly, combining prophylactic/therapeutic regimens [(-1 h)+(+24 h) or (0)+(+24 h)], or therapeutic/therapeutic regimens [(+18 h)+(+24 h)]. In general, the antiulcer agents did protect against ethanol gastric lesions regardless of the presence of the severe lung injury, in all of the used regimens. Of note, combining their prophylactic and salutary regimens (at -1 h/+24 h, or at 0/+24 h) may increase the antiulcer potential, and the effect that had been not seen already with single application, became prominent after repeated treatment.
Asunto(s)
Antiulcerosos/uso terapéutico , Etanol , Hemorragia Gastrointestinal/inducido químicamente , Hemorragia Gastrointestinal/complicaciones , Enfermedades Pulmonares/complicaciones , Animales , Hemorragia Gastrointestinal/tratamiento farmacológico , Hemorragia Gastrointestinal/prevención & control , Ácido Clorhídrico , Enfermedades Pulmonares/inducido químicamente , Masculino , Ratas , Ratas WistarRESUMEN
Anti-ulcer agents may likely attenuate lesions outside the gastrointestinal tract, since they had protected gastrectomized rats (a "direct cytoprotective effect"). Therefore, their therapeutic potential in lung/stomach lesions were shown. Rats received an intratracheal (i.t.) HCl instillation [1.5 ml/kg HCl (pH 1.75)] (lung lesion), and an intragastric (i.g.) instillation of 96% ethanol (gastric lesion; 1 ml/rat, 24 h after i.t. HCl instillation), then sacrificed 1 h after ethanol. Basically, in lung-injured rats, the subsequent ethanol-gastric lesion was markedly aggravated. This aggravation, however, in turn, did not affect the severity of the lung lesions in the further period, at least for 1 h of observation. Taking intratracheal HCl-instillation as time 0, a gastric pentadecapeptide, GEPPPGKPADDAGLV, M.W.1419, coded BPC 157 (10 microg, 10 ng, 10 pg), ranitidine (10 mg), atropine (10 mg), omeprazole (10 mg), were given [/kg, intraperitoneally (i.p.)] (i) once, only prophylactically [as a pre-treatment (at -1h)], or as a co-treatment [at 0)], or only therapeutically (at +18h or +24 h); (ii) repeatedly, combining prophylactic/therapeutic regimens [(-1 h)+(+24 h)] or [(0)+(+24 h)], or therapeutic/therapeutic regimens [(+18 h)+(+24 h)]. For all agents, combining their prophylactic and salutary regimens (at -1 h/+24 h, or at 0/+24 h) attenuated lung lesions; even if effect had been not seen already with a single application, it became prominent after repeated treatment. In single application studies, relative to controls, a co-treatment (except to omeprazole), a pre-treatment (at -1 h) (pentadecapeptide BPC 157 and atropine, but not ranitidine and omeprazole) regularly attenuated, while therapeutically, atropine (at +18 h), pentadecapeptide BPC 157 highest dose and omeprazole (at +24 h), reversed the otherwise more severe lung lesions.
Asunto(s)
Antiulcerosos/uso terapéutico , Atropina/uso terapéutico , Enfermedades Pulmonares/tratamiento farmacológico , Enfermedades Pulmonares/prevención & control , Omeprazol/uso terapéutico , Fragmentos de Péptidos/uso terapéutico , Proteínas/uso terapéutico , Ranitidina/uso terapéutico , Animales , Ácido Clorhídrico , Enfermedades Pulmonares/inducido químicamente , Masculino , Ratas , Ratas WistarRESUMEN
The focus was on haloperidol (central dopamine antagonist)-stomach lesion, a longly described suitable counterpart of dopamine blocker cysteamine-duodenal lesion. In this, the contribution of blockade of central/peripheral dopamine receptors and prostaglandins synthesis, along with influence of antiulcer agents was evaluated in mice. Male NMRI Hannnover mice were sacrificed 24 h after haloperidol (25 mg/kg b.w. i.p., given alone or with saline (haloperidol+saline) (i) or in combination (ii,iii)). Supporting central dopamine predominance for haloperidol stomach lesion induction, co-administration of peripheral dopamine receptor antagonist domperidone (5 mg/kg i.p.) (haloperidol+ domperidone) (ii), or prostaglandin synthesis inhibitor indomethacin (10 mg/kg s.c.) (haloperidol+ indomethacin) (iii) did not aggravate this lesion. (i) In haloperidol+saline challenged mice the lesions were inhibited by co-administration (/kg i.p.) of a gastric pentadecapeptide BPC 157, GlyGluProProProGlyLysProAlaAspAspAlaGlyLeuVal, M.W. 1419 (10 microg, 10 ng, 10 pg, but not 1 pg, 100 fg, 10 fg), bromocriptine (10 mg), omeprazole (10 mg, 100 mg, but not 1 mg). Atropine (10, 100, 200 mg), pirenzepine (10, 100, 200 mg), misoprostol (10, 100, 200 microg), pantoprazole (1, 10, 100 mg), lansoprazole (0.1, 1, 10 mg), cimetidine (10, 100, 200 mg) and ranitidine (10, 100, 200 mg) were not effective. (ii) Dopamine peripheral blockade influence: in haloperidol+domperidone mice, previously effective bromocriptine, pentadecapeptide BPC 157 (10 microg) or omeprazole (10 mg) did not attenuate stomach lesions. (iii) Prostaglandins synthesis blockade effect: in haloperidol+indomethacin mice, previously effective agents, bromocriptine or omeprazole were not active, while BPC 157 effect was only lessened.
Asunto(s)
Antiulcerosos/uso terapéutico , Antagonistas de Dopamina/toxicidad , Haloperidol/toxicidad , Omeprazol/análogos & derivados , Gastropatías/prevención & control , 2-Piridinilmetilsulfinilbencimidazoles , Animales , Atropina/uso terapéutico , Bencimidazoles/uso terapéutico , Bromocriptina/uso terapéutico , Cimetidina/uso terapéutico , Modelos Animales de Enfermedad , Domperidona/administración & dosificación , Antagonistas de Dopamina/administración & dosificación , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Haloperidol/administración & dosificación , Indometacina/administración & dosificación , Lansoprazol , Masculino , Ratones , Ratones Endogámicos , Misoprostol/uso terapéutico , Omeprazol/uso terapéutico , Pantoprazol , Fragmentos de Péptidos/uso terapéutico , Proteínas/uso terapéutico , Ranitidina/uso terapéutico , Gastropatías/inducido químicamente , Gastropatías/patología , Sulfóxidos/uso terapéuticoRESUMEN
Various antidepressants have antiulcer activity. Likewise, the models currently used in ulcers and depression disorders research have a considerable degree of similarity. Therefore, the possibility that depression disorders could be effectively influenced by a primary antiulcer agent with a cyto/organoprotective activity, such as the novel stomach pentadecapeptide BPC 157, was investigated in two rat depression assays. First, a forced swimming test (a Porsolt's procedure) was used. As a more severe procedure, chronic unpredictable stress (after 5 d of unpredictable stress protocol, once daily drug application during stress procedure, open field-immobility test assessment at fourth or sixth day of medication) was used. In a forced swimming test, a reduction of the immobility time in BPC 157 (10 microg, 10 ng x kg(-1) i.p.) treated rats corresponds to the activity of the 15 mg or 40 mg (i.p.) of conventional antidepressants, imipramine or nialamide, respectively, given according to the original Porsolt's protocol. In chronic unpredictable stress procedure, particular aggravation of experimental conditions markedly affected the conventional antidepressant activity, whereas BPC 157 effectiveness was continuously present. The effect of daily imipramine (30 mg) medication could be seen only after a more prolonged period, but not after a shorter period (i.e., 4-d protocol). In these conditions, no delay in the effectiveness was noted in BPC 157 medication and a reduction of the immobility of chronically stressed rats was noted after both 4 and 6 d of BPC 157 (10 microg, 10 ng) medication.
Asunto(s)
Antiulcerosos/farmacología , Antidepresivos/farmacología , Fragmentos de Péptidos/farmacología , Proteínas/farmacología , Estrés Psicológico/tratamiento farmacológico , Secuencia de Aminoácidos , Animales , Enfermedad Crónica , Evaluación Preclínica de Medicamentos , Femenino , Inmovilización , Datos de Secuencia Molecular , Ratas , Ratas Endogámicas F344 , Estrés Psicológico/psicologíaRESUMEN
Up to now, for gastric lesions potentiation or induction, as well as determination of endogenous dopamine significance, dopamine antagonist or dopamine vesicle depletor were given separately. Therefore, without combination studies, the evidence for dopamine significance remains split on either blockade of dopamine post-synaptic receptor or inhibition of dopamine storage, essentially contrasting with endogenous circumstances, where both functions could be simultaneously disturbed. For this purpose, a co-administration of reserpine and haloperidol, a dopamine granule depletor combined with a dopamine antagonist with pronounced ulcerogenic effect, was tested, and the rats were sacrificed 24 h after injurious agent(s) administration. Haloperidol (5 mg x kg(-1) b.w. i.p.), given alone, produced the lesions in all rats. Reserpine (5 mg x kg(-1) b.w. i.p.), given separately, also produced lesions. When these agents were given together, the lesions were apparently larger than in the groups injured with separate administration of either haloperidol or reserpine alone. Along with our previous results, when beneficial agents were co-administered, all dopaminomimetics (bromocriptine 10 mg, apomophine 1 mg, amphetamine 20 mg x kg(-1) i.p.) apparently attenuated the otherwise consistent haloperidol-gastric lesions. Likewise, an apparent inhibition of the reserpine-lesions was noted as well. However, if they were given in rats injured with combination of haloperidol and reserpine, their otherwise prominent beneficial effects were absent. Ranitidine (10 mg), omeprazole (10 mg), atropine (10 mg), pentadecapeptide BPC 157 (Gly-Glu-Pro-Pro-Pro-Gly-Lys-Pro-Ala-Asp-Asp-Ala-Gly-Leu-Val) (10 microg or 10 ng x kg(-1) i.p.) evidently prevented both haloperidol-gastric lesions and reserpine-gastric lesions. Confronted with potentiated lesions following a combination of haloperidol and reserpine, these agents maintained their beneficial effects, noted in the rats treated with either haloperidol or reserpine alone. The failure of dopaminomimetics could be most likely due to more extensive inhibition of endogenous dopamine system activity, and need for remained endogenous dopamine for their salutary effect, whereas the beneficial activities of ranitidine, omeprazole, atropine, pentadecapeptide BPC 157 following dopamine system inhibition by haloperidol+reserpine suggest their corresponding systems parallel those of dopamine system, and they may function despite extensive inhibition of endogenous dopamine system activity.
Asunto(s)
Antiulcerosos/uso terapéutico , Atropina/uso terapéutico , Dopamina/fisiología , Mucosa Gástrica/patología , Omeprazol/uso terapéutico , Fragmentos de Péptidos/uso terapéutico , Proteínas/uso terapéutico , Ranitidina/uso terapéutico , Úlcera Gástrica/tratamiento farmacológico , Animales , Dopaminérgicos/farmacología , Antagonistas de Dopamina , Haloperidol , Masculino , Ratas , Ratas Wistar , Reserpina , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/patologíaRESUMEN
A gastric pentadecapeptide, BPC 157, with the amino acid sequence, Gly-Glu-Pro-Pro-Pro-Gly-Lys-Pro-Ala-Asp-Asp-Ala-Gly-Leu-Val, MW 1419, known to have a variety of protective effects in gastrointestinal tract and other organs, was recently shown to particularly affect dopamine systems. For instance, it blocks the stereotypy produced acutely by amphetamine in rats, and the development of haloperidol-induced supersensitivity to amphetamine in mice. Consequently, whether pentadecapeptide BPC 157, that by itself has no cataleptogenic effect in normal animals, may attenuate the immediate effects of neuroleptics application, particularly catalepsy, was the focus of the present report. Prominent catalepsy, otherwise consistently seen in the mice treated with haloperidol (0.625, 1.25, 2.5, 5.0 and 10.0 mg/kg b.w., i.p.) and fluphenazine (0.3125, 0.625, 1.25, 2.5 and 5.0 mg/kg b.w., i.p.) after 1.5, 3, 4.5, 6 and 7.5 h following administration, was markedly attenuated when pentadecapeptide BPC 157 (10 microg or 10 ng/kg b.w., i.p.) was coadministered with the neuroleptic. The number of cataleptic mice was markedly lower throughout most of the experimental period. Moreover, on challenge with lower doses of neuroleptics, catalepsy appearance was postponed and the mice, otherwise cataleptic since the earliest period, became cataleptic later, not before 3 or 4.5 h after neuroleptic administration, especially if protected with higher pentadecapeptide dose. Besides catalepsy, coadministration of the pentadecapeptide BPC 157, given in the above mentioned doses, reduced not only catalepsy but somatosensory disorientation (for 7.5 h after administration of a neuroleptic, assessed at intervals of 1.5 h, by a simple scoring system [0-5]) in haloperidol- or fluphenazine-challenged mice as it did in mice treated with sulpiride (20, 40, 80 and 160 mg/kg b.w., i.p.) or with clozapine (25, 50 and 100 mg/kg b.w., i.p.), in which case catalepsy was absent. In other experiments, considering the gastric origin of this pentadecapeptide, the focus was shifted to the evidence that a dose of haloperidol, cataleptogenic due to dopamine receptors blockade, induces gastric ulcers in rats. Coadministration of pentadecapeptide BPC 157 (10 microg, 10 ng, 1.0 ng, 100 pg/kg b.w., i.p.) to rats completely inhibited the lesions otherwise regularly evident 24 h after haloperidol (5.0 mg/kg b.w., i.p.) in control rats (18 of 20 rats had gastric lesions). This activity accompanied the antagonism of the haloperidol catalepsy in rats (assessed at 60-min intervals from I to 5 h after haloperidol), when 10-microg- or 10-ng regimens were given (lower doses could not influence catalepsy). Together, these findings indicate that pentadecapeptide BPC 157 fully interacts with the dopamine system, both centrally and peripherally, or at least, that BPC 157 interferes with some steps involved in catalepsy and/or ulcer formation.
Asunto(s)
Catalepsia/prevención & control , Flufenazina/toxicidad , Haloperidol/toxicidad , Úlcera Péptica/prevención & control , Fragmentos de Péptidos/farmacología , Proteínas/farmacología , Animales , Antiulcerosos/síntesis química , Antiulcerosos/farmacología , Antipsicóticos/farmacología , Catalepsia/inducido químicamente , Clozapina/farmacología , Antagonistas de Dopamina/toxicidad , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Masculino , Ratones , Orientación/efectos de los fármacos , Úlcera Péptica/inducido químicamente , Fragmentos de Péptidos/síntesis química , Proteínas/síntesis química , Ratas , Ratas Wistar , Sulpirida/farmacología , Factores de TiempoRESUMEN
A clear protection of the gastrointestinal tract and an evident anti-inflammatory effect were shown for a novel stomach pentadecapeptide BPC 157 (i.p./i.g.) in comparison with several reference standards in various ulcer models along with a protection of endothelium and particular interaction with the NO-system. Thus, we evaluated whether this pentadecapeptide along with other gastroprotective agents could affect angiogenesis and the healing process in vivo using a procedure initially described by Szabo and co-workers. In each rat, two sterile sponges (1 x 1 x 0.25 cm; V = 0.25 mL) with the same quantities of BPC 157 (10 ng x mL(-1), 10 microg x mL(-1), 50 microg x kg(-1)) or reference agents (cimetidine: 10, 100, 500 mg x mL(-1); ranitidine: 2.5, 25, 250 mg x mL(-1); famotidine: 10, 50, 100 mg x mL(-1); omeprazole: 10, 50, 100 mg x mL(-1); sucralfate: 1, 5, 10 mg x mL(-1) were implanted subcutaneously in the lumbar region. The sponges were removed after 3 or 7 d, fixed in formalin, and processed for histologic and histochemical evaluation and morphometry assessment. Compared with the control values, the number of newly formed endothelial spaces inside newly formed granulation tissue was markedly increased in all animals treated with BPC 157, cimetidine, ranitidine, famotidine, sucralfate and omeprazole, a consistent finding noted after either 3 or 7 d. Compared with control values, markedly more granulation tissue was noted in the rats in the groups of animals treated with BPC 157 (50 microg) and in the rats treated with sucralfate in all dosages used, euthanized after 3 d. In all groups treated with H2-blockers however, similar values to those of controls were noted. Thus, it could be concluded that an evident angiogenic property was consistently noted for the novel pentadecapeptide BPC 157, H2-blockers (cimetidine, famotidine and ranitidine) and omeprazole, besides the well known angiogenic effect of sucralfate. Furthermore, unlike H2-blockers and omeprazole, BPC 157 stimulates the formation of granulation tissue, suggesting a particular activity, similar to that previously noted for sucralfate.
Asunto(s)
Antiulcerosos/farmacología , Fármacos Gastrointestinales/farmacología , Tejido de Granulación/efectos de los fármacos , Antagonistas de los Receptores H2 de la Histamina/farmacología , Neovascularización Fisiológica/efectos de los fármacos , Omeprazol/farmacología , Fragmentos de Péptidos/farmacología , Proteínas/farmacología , Sucralfato/farmacología , Animales , Procedimientos Quirúrgicos Dermatologicos , Tejido de Granulación/patología , Masculino , Poríferos , Prótesis e Implantes , Ratas , Ratas WistarRESUMEN
A diabetogenic alloxan regimen produced lesions in all stomachs of treated animals, either rats (200 mg x kg(-1) s.c.) or mice (400 mg x kg(-1) i.p.). In control animals, the lesions, when developed (i.e. 24 h following application), appear to be quite sustained, and consistently present also after 1 or 2 weeks. The application of the pentadecapeptide BPC 157 (10 microg or 10 ng x kg(-1) i.p. coadministered together with alloxan) would significantly attenuate these lesions' appearance. This beneficial effect seems to be present in either rats or mice and in either of the tested intervals. Importantly, the beneficial effect seems to be shared by both microgram and nanogram regimens.
Asunto(s)
Aloxano , Antiulcerosos/farmacología , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/patología , Fragmentos de Péptidos/farmacología , Proteínas/farmacología , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/patología , Animales , Masculino , Ratones , Ratones Endogámicos , Ratas , Ratas WistarRESUMEN
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.
Asunto(s)
Antiulcerosos/farmacología , Conducta Animal/efectos de los fármacos , Enfermedad de Parkinson/patología , Fragmentos de Péptidos/farmacología , Proteínas/farmacología , Gastropatías/inducido químicamente , Gastropatías/prevención & control , Animales , Temperatura Corporal/efectos de los fármacos , Catalepsia/inducido químicamente , Catalepsia/prevención & control , Hipotermia/inducido químicamente , Hipotermia/fisiopatología , Masculino , Ratones , Ratones Endogámicos , Actividad Motora/efectos de los fármacos , Enfermedad de Parkinson/mortalidad , Enfermedad de Parkinson/fisiopatología , Reserpina/farmacología , Gastropatías/patologíaRESUMEN
A superior effectiveness in various lesion assays was noted for the novel pentadecapeptide BPC 157, originated from human gastric juice protein (BPC) and claimed to be a cytoprotective agent. From this viewpoint, as a previously untreated experimental improvement to create an acid-free environmental for cytoprotection studies, total gastrectomy was done 24 hr before the ulcerogenic procedure. In the absence of stomach and gastric acid, the damaging effects of cysteamine (400 mg/kg subcutaneously, death 24 hr thereafter), to date thought to be an acid-related duodenal ulcerogen, and the BPC 157 cytoprotective effect (10 microg or 10 ng/kg intraperitoneally) were further challenged. BPC 157 was compared with reference agents [cimetidine (50), ranitidine (10), omeprazole (10), bromocriptine (10) and atropine (10) (mg/kg intraperitoneally, 1 hr before cysteamine] known to be also cytoprotective. In naive rats, with intact stomach, all of them showed a strong beneficial effect. Interestingly, in gastrectomized animals, the application of BPC 157 or the reference agents before cysteamine significantly prevented the otherwise severe duodenal lesion development noted in the control gastrectomized cysteamine rats. In groups without cysteamine, no lesions were noted (laparotomy, gastrectomy only, 24 or 48 hr postsurgical period), nor was lesion potentiation seen in cysteamine-treated laparotomized animals. In summary, these findings--equal damaging effect of cysteamine and equal protection of pentadecapeptide BPC 157 and reference agents in gastrectomized and rats with intact stomach--seem to be particularly relevant for a cytoprotective viewpoint. Without a stomach, the cysteamine damaging effect was convincingly defined as an essential gastric acid-independent injury (analogous to ethanol gastric lesions). Likewise, a high "cytoprotective capacity," apparently acid independent, common for all tested agents (novel pentadecapeptide BPC 157, cimetidine, ranitidine, omeprazole and atropine) could be clearly stressed.
Asunto(s)
Antiulcerosos/farmacología , Cisteamina/toxicidad , Úlcera Duodenal/prevención & control , Gastrectomía , Fragmentos de Péptidos/farmacología , Proteínas/farmacología , Animales , Atropina/farmacología , Bromocriptina/farmacología , Cimetidina/farmacología , Úlcera Duodenal/inducido químicamente , Femenino , Omeprazol/farmacología , Ranitidina/farmacología , Ratas , Ratas WistarRESUMEN
Besides a superior protection of the pentadecapeptide BPC 157 (an essential fragment of an organoprotective gastric juice peptide BPC) against different gastrointestinal and liver lesions, an acute anti-inflammatory and analgetic activity was also noted. Consequently, its effect on chronic inflammation lesions, such as adjuvant arthritis, and non-steroidal anti-inflammatory agents (NSAIAs)-induced gastrointestinal lesions was simultaneously studied in rats. In gastrointestinal lesions (indomethacin (30 mg/kg s.c.), aspirin (400 mg/kg i.g.) and diclofenac (125 mg/kg i.p.) studies, BPC 157 (10 micrograms or 10 ng/kg i.p.) was regularly given simultaneously and/or 1 h prior to drug application (indomethacin). In the adjuvant arthritis (tail-application of 0.2 mL of Freund's adjuvant) studies (14 days, 30 days, 1 year) BPC 157 (10 micrograms or 10 ng/kg i.p.), it was given as a single application (at 1 h either before or following the application of Freund's adjuvant) or in a once daily regimen (0-14th day, 14-30th day, 14th day-1 year). Given with the investigated NSAIAs, BPC 157 consistently reduced the otherwise prominent lesions in the stomach of the control rats, as well as the lesions in the small intestine in the indomethacin groups. In the adjuvant arthritis studies, the lesion's development seems to be considerably reduced after single pentadecapeptide medication, and even more attenuated in rats daily treated with BPC 157. As a therapy of already established adjuvant arthritis, its salutary effect consistently appeared already after 2 weeks of medication and it could be clearly seen also after 1 year of application. Taking together all these results, the data likely point to a special anti-inflammatory and mucosal integrity protective effect.
Asunto(s)
Antiinflamatorios no Esteroideos , Antiulcerosos/farmacología , Artritis Experimental/prevención & control , Fragmentos de Péptidos/farmacología , Proteínas/farmacología , Úlcera Gástrica/prevención & control , Animales , Artritis Experimental/inducido químicamente , Aspirina , Diclofenaco , Femenino , Mucosa Gástrica/patología , Indometacina , Masculino , Ratas , Ratas Wistar , Úlcera Gástrica/inducido químicamente , Factores de TiempoRESUMEN
Very recently, the integrity of capsaicin somatosensory neurons and their protection were suggested to be related to the activity in nociception of a newly discovered 15-amino acid peptide, BPC 157, shown to have strong beneficial effect on intestinal and liver lesions. Therefore, from this viewpoint, we have studied the gastroprotective effect of the pentadecapeptide BPC 157, on gastric lesions produced in rats by 96% ethanol, restraint stress, and indomethacin. The possible involvement of sensory neurons in the salutary actions of BPC 157 (10 micrograms/kg, 10 ng/kg intraperitoneally) was studied with capsaicin, which has differential effects on sensory neurons: a high dose in adult (125 mg/kg subcutaneously, 3 months old) or administration (50 mg/kg subcutaneously) to neonatal animals (age of the 7 days) destroys sensory fibers, whereas a low dose (500 micrograms/kg intraperitoneally) activates neurotransmitter release and protective effects on the mucosa. In the absence of capsaicin, BPC 157 protected gastric mucosa against ethanol, restraint, and indomethacin application. In the presence of neurotoxic doses of capsaicin, the negative influence of capsaicin on restraint, ethanol, or indomethacin lesions consistently affected salutary activity of BPC 157. However, BPC 157 protection was still evident in the capsaicin-treated rats (either treated as adults or as newborns) in all of these assays. Interestingly, after neonatal capsaicin treatment, a complete abolition of BPC gastroprotection was noted if BPC 157 was applied as a single nanogram-regimen, but the mucosal protection was fully reversed when the same dose was used daily. In line with the excitatory dose of capsaicin the beneficial effectiveness of BPC 157 appears to be increased as well. Taken together, these data provide evidence for complex synergistic interaction between the beneficial effectiveness of BPC 157 and peptidergic sensory afferent neuron activity.
Asunto(s)
Fragmentos de Péptidos/uso terapéutico , Proteínas/uso terapéutico , Úlcera Gástrica/patología , Factores de Edad , Animales , Animales Recién Nacidos , Capsaicina/toxicidad , Etanol/toxicidad , Mucosa Gástrica/patología , Indometacina/toxicidad , Masculino , Neuronas Aferentes/efectos de los fármacos , Neuronas Aferentes/fisiología , Ratas , Ratas Wistar , Restricción Física , Estómago/inervación , Úlcera Gástrica/etiología , Úlcera Gástrica/fisiopatología , Úlcera Gástrica/prevención & control , Estrés Fisiológico/complicacionesRESUMEN
The superior effectiveness of a new pentadecapeptide, BPC 157, on gastrointestinal and liver lesions, in conjunction with an antiinflammatory and analgetic activity was recently noted. In the present study, BPC 157 was tested as either a protective or healing agent in bile duct ligation-induced acute pancreatitis in rats. In addition, the positive influence of BPC 157 on concomitantly developed gastric and duodenal lesions was simultaneously investigated. BPC 157 (10 microg, 10 ng/kg body wt, intraperitoneally or intragastrically) was given prophylactically 1 hr before ligation, whereas the therapy was given once daily beginning with the 24 hr following ligation (last application 24 hr before killing). The effect was investigated at daily intervals until the end of the fifth day after ligation. In the pretreatment regimen, a strong pancreas protection was obtained. When applied in the condition of already established severe acute pancreatitis, an obvious salutory effect was consistently noted. Assessing the appearance of the necrosis, edema, neutrophils, and mononuclears, consistently less necrosis, edema, and neutrophils, but more mononuclears, were found in BPC-treated rats. Likewise, in studies of the serum amylase values, relative to control data, a markedly lower rise (BPC pretreatment regimen) as well as a worsening of the already raised values (BPC therapy regimen) was noted. Along with its beneficial effect on pancreatitis, a positive influence of BPC 157 on the gastric and duodenal lesion course in bile duct-ligated rats was noted in both the pre- and posttreatment regimen. Taken together, in further studies of acute pancreatitis therapy, BPC could be an interesting and useful agent with an additional positive impact on concomitant gastroduodenal pathology.
Asunto(s)
Pancreatitis/tratamiento farmacológico , Úlcera Péptica/tratamiento farmacológico , Fragmentos de Péptidos/uso terapéutico , Proteínas/uso terapéutico , Enfermedad Aguda , Amilasas/sangre , Animales , Edema/patología , Granulocitos/patología , Masculino , Necrosis , Páncreas/patología , Pancreatitis/complicaciones , Pancreatitis/metabolismo , Pancreatitis/patología , Úlcera Péptica/complicaciones , Úlcera Péptica/metabolismo , Úlcera Péptica/patología , Ratas , Ratas Endogámicas F344RESUMEN
Regeneration of both median nerves was studied in the rat in three different experimental models of centrocentral anastomosis through an interposed segment of pre-degenerated tibial nerve after denervation by spinal root transection. Different patterns of regeneration were observed in the anastomoses. These patterns suggest a bio-electrical polarity related to neuronal function. The present experimental model appears to offer a new opportunity to study neuronal regeneration under the influence of defined bioelectrical conditions.
Asunto(s)
Regeneración Nerviosa , Anastomosis Quirúrgica , Animales , Axones/fisiología , Electrofisiología , Nervio Mediano/citología , Nervio Mediano/fisiología , Nervio Mediano/ultraestructura , Microscopía Electrónica , Nervio Tibial/trasplanteRESUMEN
Both brachial plexuses of Wistar rats were deafferented or deefferented by disrupting their dorsal or ventral roots. At the same time, the ulnar nerves were transected and sutured. A sham group and another group in which the upper (C-5) and lower (T-1) spinal nerves were transected on both sides were included as control groups. Clear differences in the ulnar nerve regeneration rate were found between the deafferented and the deefferented animals. Ultrastructural studies disclosed signs of transient axonopathy in the nontransected fibers of the proximal segment of the ulnar nerve. The possible role of bioelectricity in the genesis of these changes is discussed.
Asunto(s)
Regeneración Nerviosa , Nervio Cubital/fisiología , Vías Aferentes/fisiología , Vías Aferentes/ultraestructura , Animales , Axones/ultraestructura , Desnervación , Vías Eferentes/fisiología , Vías Eferentes/ultraestructura , Técnicas Histológicas , Microscopía Electrónica , Factores de Tiempo , Nervio Cubital/ultraestructuraRESUMEN
The computer tomographic and angiographic features of spinal angiomas are described. The authors observed 21 cases and, on the basis of this material, they deal with the clinical features, radiological appearances, disease patterns, forms of treatment, and prognosis. CT and angiography produce a fairly uniform and typical appearance, permitting diagnosis before therapy. Problems in differential diagnosis and errors in interpretation are enumerated.