BPC 157 as a Therapy for Retinal Ischemia Induced by Retrobulbar Application of L-NAME in Rats

Abstract

Providing NO-system importance, we suggest that one single application of the NOS-blocker L-NAME may induce retinal ischemia in rats, and that the stable pentadecapeptide BPC 157 may be the therapy, since it may interact with the NO-system and may counteract various adverse effects of L-NAME application. A rat retinal ischemia study was conducted throughout 4 weeks, including fundoscopy, behavior presentation, tonometry, and histology assessment. Retrobulbar L-NAME application (5 mg/kg; 0.5 mg/0.1 ml saline/each eye) in rats immediately produced moderate generalized irregularity in the diameter of blood vessels with moderate atrophy of the optic disc and faint presentation of the choroidal blood vessels, and these lesions rapidly progressed to the severe stage. The specific L-NAME–induced vascular failure points to normal intraocular pressure (except to very transitory increase upon drug retrobulbar administration). When BPC 157 (10 μg; 10 ng/kg, as retrobulbar application, 1 μg; 1 ng/0.1 ml saline/each eye) is given at either 20 min after L-NAME or, lately, at 48 h after L-NAME, the regular retrobulbar L-NAME injection findings disappear. Instead, fundoscopy demonstrated only discrete generalized vessel caliber irregularity with mild atrophy of the optic disc, and then, quite rapidly, normal eye background and choroidal blood vessels, which remain in all of the subsequent periods. Also, histology assessment at 1, 2, and 4 weeks shows that BPC 157 counteracted the damaged inner plexiform layer and inner nuclear layer, and revealed normal retinal thickness. The poor behavioral presentation was also rescued. Thus, while further studies will be done, BPC 157 counteracted L-NAME–induced rat retinal ischemia.

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

“…An effect was also seen with parietal peritoneum removal (fewer adhesions) ( Cesar et al, 2020 ); in cecum perforation (after perforation ( Drmic et al, 2018 ), unlike empty vessels (not visible), blood vessels were filled with blood and were thereby clearly presented as blood vessels running toward the defect, with less bleeding and increased healing); in bile duct ligation-induced liver cirrhosis (prevention and reversal of portal hypertension) ( Sever et al, 2019 ). Likewise, given during reperfusion after clamping the common carotid arteries, BPC 157 reduced stroke (i.e., both early and delayed hippocampal neural damage, achieving full functional recovery in the Morris water maze test, inclined beam-walking test, and lateral push test) ( Vukojevic et al, 2020 ) or reduced L-NAME-induced retinal ischemia in rats ( Zlatar et al, 2021 ).…”

Complex Syndrome of the Complete Occlusion of the End of the Superior Mesenteric Vein, Opposed with the Stable Gastric Pentadecapeptide BPC 157 in Rats

“…In hippocampal tissues, mRNA expression studies at 1 and 24 h, and strongly elevated (Egr1, Akt1, Kras, Src, Foxo, Srf, Vegfr2, Nos3, Nos1) and decreased (Nos2, Nfkb) gene expression (Mapk1 not activated) may be a way how BPC 157 may act [20]. Counteraction of the retinal ischemia and severe damage induced by retrobulbar application of L-NAME may provide a possible important analogy [61].…”

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

“…The activation of the collateral loops occurred in a particular manner (i.e., left superior caval vein-azygos vein-inferior caval vein shunt (Budd–Chiari syndrome) [ 5 ] and recruited (para)sagittal venous collateral circulation (central venous occlusion)) [ 8 ]. Thus, BPC 157 activated a “bypassing key” (i.e., collateral pathways reliant on the injurious occlusion) [ 2 , 3 , 4 , 5 , 6 , 7 , 8 ], suggesting the beneficial effects commonly noted in other vascular injury studies [ 21 , 22 , 23 , 24 , 25 , 26 ], which was in essential competition with the commonly present Virchow’s triad (endothelium lesion, hypercoagulability, and stasis) and its resolution. In addition, BPC 157 interacts with several molecular pathways [ 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ].…”