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

Abstract

Due to endothelial impairment, high-dose lithium may produce an occlusive-like syndrome, comparable to permanent occlusion of major vessel-induced syndromes in rats; intracranial, portal, and caval hypertension, and aortal hypotension; multi-organ dysfunction syndrome; brain, heart, lung, liver, kidney, and gastrointestinal lesions; arterial and venous thrombosis; and tissue oxidative stress. Stable gastric pentadecapeptide BPC 157 may be a means of therapy via activating loops (bypassing vessel occlusion) and counteracting major occlusion syndromes. Recently, BPC 157 counteracted the lithium sulfate regimen in rats (500 mg/kg/day, ip, for 3 days, with assessment at 210 min after each administration of lithium) and its severe syndrome (muscular weakness and prostration, reduced muscle fibers, myocardial infarction, and edema of various brain areas). Subsequently, BPC 157 also counteracted the lithium-induced occlusive-like syndrome; rapidly counteracted brain swelling and intracranial (superior sagittal sinus) hypertension, portal hypertension, and aortal hypotension, which otherwise would persist; counteracted vessel failure; abrogated congestion of the inferior caval and superior mesenteric veins; reversed azygos vein failure; and mitigated thrombosis (superior mesenteric vein and artery), congestion of the stomach, and major hemorrhagic lesions. Both regimens of BPC 157 administration also counteracted the previously described muscular weakness and prostration (as shown in microscopic and ECG recordings), myocardial congestion and infarction, in addition to edema and lesions in various brain areas; marked dilatation and central venous congestion in the liver; large areas of congestion and hemorrhage in the lung; and degeneration of proximal and distal tubules with cytoplasmic vacuolization in the kidney, attenuating oxidative stress. Thus, BPC 157 therapy overwhelmed high-dose lithium intoxication in rats.

Stable Gastric Pentadecapeptide BPC 157 Therapy for Primary Abdominal Compartment Syndrome in Rats

“…Thus, it may be that maintained increased intra-abdominal pressure causes widespread dysfunction, which would be similar to the severe syndromes observed in rats with the occlusion of peripheral vessels ( Vukojevic et al, 2018 ; Gojkovic et al, 2020 ; Kolovrat et al, 2020 ; Knezevic et al, 2021a ; Knezevic et al, 2021a ; Knezevic et al, 2021b ) and central vessels ( Gojkovic et al, 2021a ) or after the intragastric application of absolute alcohol ( Gojkovic et al, 2021b ) and intraperitoneal application of the lithium overdose ( Strbe et al, 2021 ). These peripheral and central deficits can include severe gastrointestinal lesions, intracranial (superior sagittal sinus) hypertension, brain swelling and lesions, portal and caval hypertension, aortic hypotension, peripheral and central thrombosis, inferior caval vein and superior mesenteric vein congestion, azygos vein failure, electrocardiogram (ECG) disturbances, and heart, lung, liver, and kidney lesions ( Vukojevic et al, 2018 ; Gojkovic et al, 2020 ; Kolovrat et al, 2020 ; Gojkovic et al, 2021a ; Knezevic et al, 2021a ; Knezevic et al, 2021a ; Gojkovic et al, 2021b ; Knezevic et al, 2021b ; Strbe et al, 2021 ). Syndrome development and treatment with BPC 157 have been demonstrated in a variety of procedures inducing vessel occlusion ( Vukojevic et al, 2018 ; Gojkovic et al, 2020 ; Kolovrat et al, 2020 ; Gojkovicc et al, 2021a ; Knezevic et al, 2021a ; Knezevic et al, 2021a ; Gojkovic et al, 2021b ; Knezevic et al, 2021b ; Strbe et al, 2021 ).…”

“…We suggest that abdominal compartment syndrome ( Depauw et al, 2019 ) is a multiple occlusion syndrome. Therefore, it is thought that by improving the function of the venous system with the stable gastric pentadecapeptide BPC 157 ( Vukojevic et al, 2018 ; Gojkovic et al, 2020 ; Kolovrat et al, 2020 ; Gojkovic et al, 2021a ; Knezevic et al, 2021a ; Knezevic et al, 2021a ; Gojkovic et al, 2021b ; Knezevic et al, 2021b ; Strbe et al, 2021 ), the chain of harmful events in abdominal compartment syndrome can be reversed.…”

“…The stable gastric pentadecapeptide BPC 157 was chosen and tested in this study due to its beneficial effects in major vessel occlusion syndromes ( Vukojevic et al, 2018 ; Gojkovic et al, 2020 ; Kolovrat et al, 2020 ; Gojkovic et al, 2021a ; Knezevic et al, 2021a ; Knezevic et al, 2021a ; Gojkovic et al, 2021b ; Knezevic et al, 2021b ; Strbe et al, 2021 ) and as a prototypic cytoprotective peptide (for review, see Sikiric et al, 1993a ; Sikiric et al, 2006 ; Sikiric et al, 2010 ; Sikiric et al, 2011 ; Sikiric et al, 2012 ; Sikiric et al, 2013 ; Sikiric et al, 2014 ; Sikiric et al, 2016 ; Sikiric et al, 2017 ; Sikiric et al, 2018 ; Sikiric et al, 2020a ; Sikiric et al, 2020b ; Seiwerth et al, 2014 ; Seiwerth et al, 2018 ; Seiwerth et al, 2021 ; Kang et al, 2018 ; Park et al, 2020 ; Gwyer et al, 2019 , Vukojevic et al, 2022 ).…”

“…To fully model intra-abdominal hypertension syndrome (continuous intraperitoneal insufflation of ordinary air), these occlusion syndromes have been induced peripherally ( Vukojevic et al, 2018 ; Gojkovic et al, 2020 ; Kolovrat et al, 2020 ; Knezevic et al, 2021a ; Knezevic et al, 2021a ; Knezevic et al, 2021b ) or centrally ( Gojkovic et al, 2021a ) and both peripherally and centrally ( Gojkovic et al, 2021b ; Strbe et al, 2021 ). Specific occlusion syndrome induction can be performed by the occlusion of a major vein ( Vukojevic et al, 2018 ; Gojkovic et al, 2020 ; Gojkovic et al, 2021a ; Knezevic et al, 2021b ) or an artery ( Knezevic et al, 2021a ), or with both artery and vein occlusion ( Kolovrat et al, 2020 ; Knezevic et al, 2021a ), or by intragastric application of absolute alcohol ( Gojkovic et al, 2021b ) and intraperitoneal application of lithium overdose ( Strbe et al, 2021 ).…”

“…Considering the effects of BPC 157 therapy peripherally and centrally ( Vukojevic et al, 2018 ; Gojkovic et al, 2020 ; Kolovrat et al, 2020 ; Gojkovic et al, 2021a ; Knezevic et al, 2021a ; Knezevic et al, 2021a ; Gojkovic et al, 2021b ; Knezevic et al, 2021b ; Strbe et al, 2021 ), in rats with severely increased intra-abdominal pressure, i.e., primary abdominal compartment syndrome, we attempted to introduce a therapy for compressed essential vessel tributaries, both arterial and venous (peripherally and centrally), due to occluded major veins and arteries, in order to prevent the consequent noxious syndrome, both peripherally and centrally. Otherwise, intra-abdominal hypertension adversely affects many organs, such as the brain, heart, lungs, kidneys, and gastrointestinal tract ( Cullen et al, 1989 ), progressing to lethal levels.…”