Selye's syndrome produced by diverse nocuous agents and "response to damage as such" means Selye's stress triad in stress coping response to reestablish homeostasis. Logically, from the gastrointestinal tract viewpoint, such organoprotective/healing response implies the angiogenic growth factors that commonly signify the healing. Thereby, the gastric pentadecapeptide BPC 157-organoprotection (huge range of beneficial effects) signifies the Selye's stress concept/stress coping response implemented in and from gastrointestinal tract, and BPC 157 as an integrative mediator that integrates the adaptive bodily response to stress. In clinical trials without side effects, LD1 not achieved, BPC 157 healing in gastrointestinal tract, and particularly the healing of the extragastrointestinal tissues (i.e., skin/tendon/ligament/muscle/bone; nerve; cornea/ brain) were referred throughout its integrative capabilities (i.e., ulcerative colitis/multiple sclerosis model equally counteracted), native in gastrointestinal tract, stability in human gastric juice (and thereby, strong efficacy and applicability), its relevance for dopamine-system function (and thereby, counteracting effects of dopamine-system dysfunction and overfunction, centrally and peripherally (mucosa maintenance); interaction with serotonin- and GABA-system)), afforded cytoprotection/adaptive cytoprotection/organoprotection (and thereby, beneficial effects on gastric and whole intestinal tract lesions and adaptation, wounds and fistulas healing, blood vessels, somatosensory neurons, NSAIDs-side effects (including also pancreas, liver, brain lesions, and blood disturbances, prolonged bleeding, thrombocytopenia, thrombosis)). Further, we combine such gut-brain axis and the NO-system where BPC 157 counteracts complications of either L-NAME application (i.e., various lesions aggravation, hypertension) or Larginine application (i.e., hypotension, prolonged bleeding, thrombocytopenia). Also, BPC 157 particularly affects genes functions (i.e., Fos, c-Jun, Egr-1), all together suggestive for an indicative generalization. Thus, we could suggest gastric pentadecapeptide BPC 157 and BPC 157 induced-organoprotection as integrative mediator that integrates the adaptive bodily response to stress, and thereby practically applied in further therapy and in effective realization of Selye's stress response.
The ulcerogenic potential of dopamine antagonists and L-NAME in rats provides unresolved issues of anti-emetic neuroleptic application in both patients and experimental studies. Therefore, in a 1-week study, we examined the pressures within the lower oesophageal and the pyloric sphincters in rats [assessed manometrically (cm HO)] after dopamine neuroleptics/prokinetics, L-NAME, L-arginine and stable gastric pentadecapeptide BPC 157 were administered alone and/or in combination. Medication (/kg) was given once daily intraperitoneally throughout the 7 days, with the last dose at 24 h before pressure assessment. Given as individual agents to healthy rats, all dopamine antagonists (central [haloperidol (6.25 mg, 16 mg, 25 mg), fluphenazine (5 mg), levomepromazine (50 mg), chlorpromazine (10 mg), quetiapine (10 mg), olanzapine (5 mg), clozapine (100 mg), sulpiride (160 mg), metoclopramide (25 mg)) and peripheral(domperidone (10 mg)], L-NAME (5 mg) and L-arginine (100 mg) decreased the pressure within both sphincters. As a common effect, this decreased pressure was rescued, dose-dependently, by BPC 157 (10 µg, 10 ng) (also note that L-arginine and L-NAME given together antagonized each other's responses). With haloperidol, L-NAME worsened both the lower oesophageal and the pyloric sphincter pressure, while L-arginine ameliorated lower oesophageal sphincter but not pyloric sphincter pressure, and antagonized L-NAME effect. With domperidone, L-arginine originally had no effect, while L-NAME worsened pyloric sphincter pressure. This effect was opposed by L-arginine. All these effects were further reversed towards a stronger beneficial effect, close to normal pressure values, by the addition of BPC 157. In addition, NO level was determined in plasma, sphincters and brain tissue. Thiobarbituric acid reactive substances (TBARS) were also assessed. Haloperidol increased NO levels (in both sphincters, the plasma and brain), consistently producing increased TBARS levels in the plasma, sphincters and brain tissues. These effects were all counteracted by BPC 157 administration. In conclusion, we revealed that BPC 157 counteracts the anti-emetic neuroleptic class side effect of decreased pressure in sphincters and the dopamine/NO-system/BPC 157 relationship.
AIMTo counteract/reveal celecoxib-induced toxicity and NO system involvement.METHODSCelecoxib (1 g/kg b.w. ip) was combined with therapy with stable gastric pentadecapeptide BPC 157 (known to inhibit these lesions, 10 μg/kg, 10 ng/kg, or 1 ng/kg ip) and L-arginine (100 mg/kg ip), as well as NOS blockade [N(G)-nitro-L-arginine methyl ester (L-NAME)] (5 mg/kg ip) given alone and/or combined immediately after celecoxib. Gastrointestinal, liver, and brain lesions and liver enzyme serum values in rats were assessed at 24 h and 48 h thereafter.RESULTSThis high-dose celecoxib administration, as a result of NO system dysfunction, led to gastric, liver, and brain lesions and increased liver enzyme serum values. The L-NAME-induced aggravation of the lesions was notable for gastric lesions, while in liver and brain lesions the beneficial effect of L-arginine was blunted. L-arginine counteracted gastric, liver and brain lesions. These findings support the NO system mechanism(s), both NO system agonization (L-arginine) and NO system antagonization (L-NAME), that on the whole are behind all of these COX phenomena. An even more complete antagonization was identified with BPC 157 (at both 24 h and 48 h). A beneficial effect was evident on all the increasingly negative effects of celecoxib and L-NAME application and in all the BPC 157 groups (L-arginine + BPC 157; L-NAME + BPC 157; L-NAME + L-arginine + BPC 157). Thus, these findings demonstrated that BPC 157 may equally counteract both COX-2 inhibition (counteracting the noxious effects of celecoxib on all lesions) and additional NOS blockade (equally counteracting the noxious effects of celecoxib + L-NAME).CONCLUSIONBPC 157 and L-arginine alleviate gastrointestinal, liver and brain lesions, redressing NSAIDs’ post-surgery application and NO system involvement.
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