Robert’s Intragastric Alcohol-Induced Gastric Lesion Model as an Escalated General Peripheral and Central Syndrome, Counteracted by the Stable Gastric Pentadecapeptide BPC 157

Abstract

We redefined Robert’s prototypical cytoprotection model, namely the intragastric administration of 96% alcohol in order to generate a general peripheral and central syndrome similar to that which occurs when major central or peripheral veins are occluded in animal models. With this redefinition, we used Robert’s model to examine the cytoprotective effects of the stable gastric pentadecapeptide BPC 157. The intragastric administration of alcohol induced gastric lesions, intracranial (superior sagittal sinus) hypertension, severe brain swelling and lesions, portal and vena caval hypertension, aortal hypotension, severe thrombosis, inferior vena cava and superior mesenteric vein congestion, azygos vein failure (as a failed collateral pathway), electrocardiogram disturbances, and heart, lung, liver and kidney lesions. The use of BPC 157 therapy (10 µg/kg or 10 ng/kg given intraperitoneally 1 min after alcohol) counteracted these deficits rapidly. Specifically, BPC 157 reversed brain swelling and superior mesenteric vein and inferior vena caval congestion, and helped the azygos vein to recover, which improved the collateral blood flow pathway. Microscopically, BPC 157 counteracted brain (i.e., intracerebral hemorrhage with degenerative changes of cerebral and cerebellar neurons), heart (acute subendocardial infarct), lung (parenchymal hemorrhage), liver (congestion), kidney (congestion) and gastrointestinal (epithelium loss, hemorrhagic gastritis) lesions. In addition, this may have taken place along with the activation of specific molecular pathways. In conclusion, these findings clarify and extend the theory of cytoprotection, offer an approach to its practical application, and establish BPC 157 as a prospective cytoprotective treatment.

Over-Dose Lithium Toxicity as an Occlusive-like Syndrome in Rats and Gastric Pentadecapeptide BPC 157

“…We hypothesized that the higher therapeutic and supratherapeutic lithium levels known to impair endothelium-dependent blood vessel relaxation, as an additional mechanism contributing to lithium toxicity (e.g., renal and neurological) [ 1 ], may be related to a worse syndrome of vascular impairment—an “occlusion-like” syndrome [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 ]—and thereby extensive lithium toxicity, peripherally and centrally.…”

“…These findings [ 15 ] were suggestive of additional brain, heart, lung, liver, kidney, and gastrointestinal tract lesions, which may, due to the lithium-induced vascular impairment [ 1 ], produce an additional high-dose lithium syndrome, i.e., an occlusion-like syndrome, with intracranial, portal and caval hypertension; aortal hypotension; and generalized peripheral and central thromboses. To date, the possibility that lithium toxicity consequently appears as an occlusion-like syndrome [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 ] has not been investigated or appropriately combined with lithium toxicity. The multi-organ dysfunction syndrome due to lithium-induced vascular impairment [ 1 ] may be akin to those syndromes induced in rats with occluded major vessels [ 2 , 3 , 4 , 5 , 6 , 7 , 8 ], peripherally [ 2 , 3 , 4 , 5 , 6 , 7 ] and centrally [ 8 ].…”

“…Because BPC 157 therapy consistently counteracted all of these occlusive syndromes [ 2 , 3 , 4 , 5 , 6 , 7 , 8 ], it may be effective in rats with high-dose lithium intoxication and may largely counteract the lithium syndrome. In support of this idea, a multi-organ dysfunction syndrome characterized by lithium-induced vascular impairment [ 1 ], alcohol-induced vascular impairment [ 9 ], and absolute alcohol instillation in the rat stomach, produced a similar occlusion-like syndrome of peripheral and central multi-organ dysfunction; intracranial, portal, and caval hypertension; aortal hypotension; and generalized peripheral and central thromboses. BPC 157 therapy fully counteracted these effects [ 9 ].…”

“…However, it is nonetheless intended that the therapy can be used to elucidate the activated rescuing bypassing collateral pathway as a key to the recovery of lithium toxicity as an occlusive-like syndrome. The activated rescuing bypassing collateral pathway (i.e., the azygos vein, and the inferior caval vein–azygos vein–superior caval vein pathway) was also involved in the recovery of the intragastric absolute alcohol-induced occlusion-like syndrome [ 9 ]. We hypothesized that, in accordance with its previous therapeutic effects in occlusive syndromes [ 2 , 3 , 4 , 5 , 6 , 7 , 8 ] and alcohol-induced occlusion-like syndrome [ 9 ], BPC 157 administration would counteract both peripheral (portal hypertension, caval hypertension, and aortal hypotension) and central disturbances (i.e., brain swelling/lesions and intracranial hypertension), in addition to organ lesions and oxidative stress, in rats treated with a high-dose lithium therapy.…”

Stable Gastric Pentadecapeptide BPC 157 as a Therapy for the Disable Myotendinous Junctions in Rats

“…Interestingly, in addition to the muscle and tendon healing [18][19][20][21][22], BPC 157 has a particularly beneficial effect against fibrosis also in rat bile duct ligation-induced liver cirrhosis [55]. Finally, the most recent therapy evidence as follow up of the above mentioned recovered endothelium function [47,56], consistently noted in major vessel occlusion studies [52][53][54][57][58][59][60]96], peripherally [52,54,[57][58][59][60] or centrally [53], and peripherally and centrally [96], shows that BPC 157 therapy may activate collateral vascular pathways, which are reliant to injury occlusion. Consequently, BPC 157 therapy ameliorated or even counteracted various severe vessel occlusive syndromes [52][53][54][57][58][59][60]96].…”