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

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1547
Author(s):  
Mladen Japjec ◽  
Katarina Horvat Pavlov ◽  
Andreja Petrovic ◽  
Mario Staresinic ◽  
Bozidar Sebecic ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Quadriceps Tendon ◽  
Quadriceps Muscle ◽  
Myotendinous Junction ◽  
Mrna Levels ◽  
Bpc 157 ◽  
The Disabled ◽  
Pentadecapeptide Bpc 157 ◽  
Cox 2 ◽  
Myotendinous Junctions

(1) Aim: The stable gastric pentadecapeptide BPC 157 is known to heal transected muscle, tendon, and ligament. Thereby, in this study, we investigated the effect of BPC 157 on the dissection of the quadriceps tendon from the quadriceps muscle in rats. (2) Materials and Methods: Myotendinous junction defect, which cannot heal spontaneously in rats, as evidenced with consistent macro/microscopic, biomechanical, functional assessments, eNOS, and COX-2 mRNA levels and oxidative stress and NO-levels in the myotendinous junctions. BPC 157 (10 µg/kg, 10 ng/kg) regimen was given (i) intraperitoneally, first application immediately after surgery, last 24 h before sacrifice; (ii) per-orally, in drinking water (0.16 µg/mL, 0.16 ng/mL, 12 mL/rat/day), till the sacrifice at 7, 14, 28 and 42 postoperative days. (3) Results: These BPC 157 regimens document prominent therapy effects (macro/microscopic, biomechanical, functional much like eNOS and COX-2 mRNA levels and counteracted oxidative stress and NO-levels in the myotendinous junctions), while controls have a poor presentation. Especially, in rats with the disabled myotendinous junction, along with full functional recovery, BPC 157 counteracts muscle atrophy that is regularly progressive and brings muscle presentation close to normal. Accordingly, unlike the perilous course in controls, those rats, when receiving BPC 157 therapy, exhibit a smaller defect, and finally defects completely disappear. Microscopically, there are no more inflammatory infiltrate, well-oriented recovered tissue of musculotendon junction appears in BPC 157 treated rats at the 28 days and 42 days. (4) Conclusions: BPC 157 restores myotendinous junction in accordance with the healing of the transected muscle, tendon, and ligament.

Effective therapy of transected quadriceps muscle in rat: Gastric pentadecapeptide BPC 157

2006 ◽  
Vol 24 (5) ◽  
pp. 1109-1117 ◽  
Author(s):  
Mario Staresinic ◽  
Igor Petrovic ◽  
Tomislav Novinscak ◽  
Ivana Jukic ◽  
Damira Pevec ◽  
...  
Keyword(s):  
Quadriceps Muscle ◽  
Effective Therapy ◽  
Bpc 157 ◽  
Pentadecapeptide Bpc 157

Red wine extract protects against oxidative-stress-induced endothelial senescence

2012 ◽  
Vol 123 (8) ◽  
pp. 499-507 ◽  
Author(s):  
Ilse P. G. Botden ◽  
Hisko Oeseburg ◽  
Matej Durik ◽  
Frank P. J. Leijten ◽  
Leonie C. Van Vark-Van Der Zee ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Red Wine ◽  
Umbilical Vein ◽  
Critical Role ◽  
Sirtuin 1 ◽  
Mrna Levels ◽  
Nitric Oxide Synthase Inhibitor ◽  
Age Related ◽  
Cox 2

Red wine polyphenols may preserve endothelial function during aging. Endothelial cell senescence enhances age-related endothelial dysfunction. We investigated whether RWE (red wine extract) prevents oxidative-stress-induced senescence in HUVECs (human umbilical-vein endothelial cells). Senescence was induced by exposing HUVECs to tBHP (t-butylhydroperoxide), and quantified by senescence-associated β-galactosidase staining. RWE (0–50 μg/ml) concentration dependently decreased senescence by maximally 33±7.1%. RWE prevented the senescence-associated increase in p21 protein expression, inhibited tBHP-induced DNA damage of endothelial cells and induced relaxation of PCAs (porcine coronary arteries). Inhibition of SIRT1 (sirtuin 1) by sirtinol partially reversed the effect of RWE on tBHP-induced senescence, whereas both the NOS (nitric oxide synthase) inhibitor L-NMMA (NG-monomethyl-L-arginine) and the COX (cyclo-oxygenase) inhibitor indomethacin fully inhibited it. Furthermore, incubation of HUVECs with RWE increased eNOS (endothelial NOS) and COX-2 mRNA levels as well as phosphorylation of eNOS at Ser1177. RWE protects endothelial cells from tBHP-induced senescence. NO and COX-2, in addition to activation of SIRT1, play a critical role in the inhibition of senescence induction in human endothelial cells by RWE.

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

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 1029
Author(s):  
Mario Knezevic ◽  
Slaven Gojkovic ◽  
Ivan Krezic ◽  
Helena Zizek ◽  
Hrvoje Vranes ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Flow ◽  
Gastrointestinal Tract ◽  
Superior Mesenteric Vein ◽  
Superior Sagittal Sinus ◽  
Bpc 157 ◽  
Mesenteric Vein ◽  
Sagittal Sinus ◽  
Pentadecapeptide Bpc 157 ◽  
And Oxidative Stress

Background. Gastric pentadecapeptide BPC 157 therapy in rats compensated irremovable occlusion of various vessels and counteracted the consequent multiorgan dysfunction syndromes by activation of the corresponding collateral bypassing loops. Thus, we used BPC 157 therapy against the irremovable occlusion of the end of the superior mesenteric vein. Methods. Assessments, for 30 min (gross recording, venography, ECG, pressure, microscopy, biochemistry, and oxidative stress) include the portal and caval hypertension, aortal hypotension, and centrally, the superior sagittal sinus hypertension, systemic arterial and venous thrombosis, ECG disturbances, MDA-tissue increase, and heart, lung, liver, kidney and gastrointestinal tract, in particular, and brain (cortex (cerebral, cerebellar), hypothalamus/thalamus, hippocampus) lesions. Rats received BPC 157 medication (10 µg/kg, 10 ng/kg) intraperitoneally at 1 or 15 min ligation time. Results. BPC 157 rapidly activated the superior mesenteric vein–inferior anterior pancreati-coduodenal vein–superior anterior pancreaticoduodenal vein–pyloric vein–portal vein pathway, reestablished superior mesenteric vein and portal vein connection and reestablished blood flow. Simultaneously, toward inferior caval vein, an additional pathway appears via the inferior mesenteric vein united with the middle colic vein, throughout its left colic branch to ascertain alternative bypassing blood flow. Consequently, BPC 157 acts peripherally and centrally, and counteracted the intracranial (superior sagittal sinus), portal and caval hypertension, aortal hypotension, ECG disturbances attenuated, abolished progressing venous and arterial thrombosis. Additionally, BPC 157 counteracted multiorgan dysfunction syndrome, heart, lung, liver, kidney and gastrointestinal tract, and brain lesions, and oxidative stress in tissues. Conclusion. BPC 157 therapy may be specific management also for the superior mesenteric vein injuries.

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

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1506
Author(s):  
Sanja Strbe ◽  
Slaven Gojkovic ◽  
Ivan Krezic ◽  
Helena Zizek ◽  
Hrvoje Vranes ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Azygos Vein ◽  
High Dose ◽  
Muscular Weakness ◽  
Brain Areas ◽  
Vessel Occlusion ◽  
Bpc 157 ◽  
Gastrointestinal Lesions ◽  
Major Vessel ◽  
Pentadecapeptide Bpc 157

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.

Antitumor activity of zinc nanoparticles synthesized with berberine on human epithelial colorectal adenocarcinoma (Caco-2) cells through acting on Cox-2/NF-kB and p53 pathways

2021 ◽  
Vol 21 ◽  
Author(s):  
Mohamed S. Othman ◽  
Amal H. Al-Bagawi ◽  
Sofian T. Obeidat ◽  
Mohamed A. Fareid ◽  
Ola A. Habotta ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Tumor Cells ◽  
Mtt Assay ◽  
Caspase 3 ◽  
Therapeutic Potential ◽  
Vero Cells ◽  
Suppressor Gene ◽  
Mrna Levels ◽  
Zinc Nanoparticles ◽  
Cox 2

Background: Drawbacks and side effects of currently available therapies to colorectal cancer (CRC) devoted the researchers to search for new therapeutic strategies. Objective: This study was designed to investigate the effects of zinc nanoparticles biosynthesized with berberine (ZnNPs-BER) on Caco-2 cells compared to 5-Fluorouracil (5-FU) and explore the possible underlying pathways. Methods: Caco-2 and Vero cells were treated with 5-FU, BER, or ZnNPs-BER for 24 h. Cell viability was measured by MTT assay. Oxidative stress and apoptotic markers and cell cycle were determined. Additionally, Cox-2 and NF-kB levels were also measured. Results: The IC50 of 5-FU, BER, and ZnNPs-BER on Caco-2 cells were 34.65 µM, 19.86 µg/ml and 10.49 µg/ml, respectively by MTT assay. The IC50 value for 5-FU in Vero cells was 21.7 μg/ml, however, BER and BER-ZnNPs treatment showed non-toxic effects to the Vero cells. Further, ZnNPs-BER exerted significant induction of ROS besides exhaustion of the antioxidant capacity of tumor cells indicated by declined GSH and elevated NO and MDA contents. Marked increments in levels of Bax and caspase-3 were detected together with declines in Bcl-2 levels in Caco-2 cells submitted to BER-ZnNPs therapy. On the molecular basis, upregulation in mRNA levels of pro-apoptotic genes (Bax, caspase-3, and tumor suppressor gene p53) with downregulation in the antiapoptotic gene (Bcl-2) were observed in ZnNPs-BER treated Caco-2 cells. Furthermore, ZnNPs-BER showed more pronounced effects on apoptosis increased cell percentage in the S and subG1 phases. In addition, green synthesis of ZnNPs with BER showed notable induction of Cox2 and NF-kB in Caco-2 cells. Conclusion: Therefore, the antitumor potential of ZnNPs-BER in colon cancer cells may be endorsed for induction of oxidative stress, inflammation, and apoptotic changes in tumor cells. Our study documents the new therapeutic potential of Zn nanoparticles conjugated with BER, as a new option for combined chemotherapy.

scholarly journals Occluded Superior Mesenteric Artery and Vein. Therapy with the Stable Gastric Pentadecapeptide BPC 157

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 792
Author(s):  
Mario Knezevic ◽  
Slaven Gojkovic ◽  
Ivan Krezic ◽  
Helena Zizek ◽  
Dominik Malekinusic ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mesenteric Artery ◽  
Superior Mesenteric Vein ◽  
Superior Sagittal Sinus ◽  
Bpc 157 ◽  
Mesenteric Vein ◽  
Sagittal Sinus ◽  
Multiple Organs ◽  
Pentadecapeptide Bpc 157 ◽  
And Oxidative Stress

Background. We investigated the occluded essential vessel tributaries, both arterial and venous, occluded superior mesenteric vein and artery in rats, consequent noxious syndrome, peripherally and centrally. As therapy, we hypothesized the rapidly activated alternative bypassing pathways, arterial and venous, and the stable gastric pentadecapeptide BPC 157 since it rapidly alleviated venous occlusion syndromes. Methods. Assessments were performed for 30 min (gross recording, venography, ECG, pressure, microscopy, biochemistry, and oxidative stress), including portal hypertension, caval hypertension, aortal hypotension, and centrally, the superior sagittal sinus hypertension; systemic arterial and venous thrombosis, ECG disturbances, MDA-tissue increase, the multiple organs lesions, heart, lung, liver, kidney and gastrointestinal tract, including brain (swelling, and cortex (cerebral, cerebellar), hypothalamus/thalamus, hippocampus lesions). Rats received BPC 157 medication (10 µg/kg, 10 ng/kg) intraperitoneally at 1 min ligation-time. Results. BPC 157 rapidly activated collateral pathways. These collateral loops were the superior mesenteric vein-inferior anterior pancreaticoduodenal vein-superior anterior pancreaticoduodenal vein-pyloric vein-portal vein pathway, an alternative pathway toward inferior caval vein via the united middle colic vein and inferior mesenteric vein through the left colic vein, and the inferior anterior pancreaticoduodenal artery and inferior mesenteric artery. Consequently, BPC 157 counteracted the superior sagittal sinus, portal and caval hypertension, aortal hypotension, progressing venous and arterial thrombosis peripherally and centrally, ECG disturbances attenuated. Markedly, the multiple organs lesions, heart, lung, liver, kidney, and gastrointestinal tract, in particular, as well as brain lesions, and oxidative stress in tissues were attenuated. Conclusions. BPC 157 therapy rapidly recovered rats, which have complete occlusion of the superior mesenteric vein and artery.

Copper-dependent ATP7B up-regulation drives the resistance of TMEM16A-overexpressing head-and-neck cancer models to platinum toxicity

2019 ◽  
Vol 476 (24) ◽  
pp. 3705-3719 ◽  
Author(s):  
Avani Vyas ◽  
Umamaheswar Duvvuri ◽  
Kirill Kiselyov
Keyword(s):  
Oxidative Stress ◽  
Head And Neck ◽  
Transcriptional Activation ◽  
Platinum Resistance ◽  
Mrna Levels ◽  
Strong Positive Correlation ◽  
Platinum Compounds ◽  
Copper Chelation ◽  
Novel Approach ◽  
Cancer Models

Platinum-containing drugs such as cisplatin and carboplatin are routinely used for the treatment of many solid tumors including squamous cell carcinoma of the head and neck (SCCHN). However, SCCHN resistance to platinum compounds is well documented. The resistance to platinum has been linked to the activity of divalent transporter ATP7B, which pumps platinum from the cytoplasm into lysosomes, decreasing its concentration in the cytoplasm. Several cancer models show increased expression of ATP7B; however, the reason for such an increase is not known. Here we show a strong positive correlation between mRNA levels of TMEM16A and ATP7B in human SCCHN tumors. TMEM16A overexpression and depletion in SCCHN cell lines caused parallel changes in the ATP7B mRNA levels. The ATP7B increase in TMEM16A-overexpressing cells was reversed by suppression of NADPH oxidase 2 (NOX2), by the antioxidant N-Acetyl-Cysteine (NAC) and by copper chelation using cuprizone and bathocuproine sulphonate (BCS). Pretreatment with either chelator significantly increased cisplatin's sensitivity, particularly in the context of TMEM16A overexpression. We propose that increased oxidative stress in TMEM16A-overexpressing cells liberates the chelated copper in the cytoplasm, leading to the transcriptional activation of ATP7B expression. This, in turn, decreases the efficacy of platinum compounds by promoting their vesicular sequestration. We think that such a new explanation of the mechanism of SCCHN tumors’ platinum resistance identifies novel approach to treating these tumors.

scholarly journals Creatine Alleviates Doxorubicin-Induced Liver Damage by Inhibiting Liver Fibrosis, Inflammation, Oxidative Stress, and Cellular Senescence

Nutrients ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 41
Author(s):  
Nouf Aljobaily ◽  
Michael J. Viereckl ◽  
David S. Hydock ◽  
Hend Aljobaily ◽  
Tsung-Yen Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Methylation ◽  
Body Weight ◽  
Liver Fibrosis ◽  
Liver Damage ◽  
Cellular Senescence ◽  
Weight Ratio ◽  
Mrna Levels ◽  
Body Weight Ratio ◽  
Chromosomal Stability

Background: Treatment with the chemotherapy drug doxorubicin (DOX) may lead to toxicities that affect non-cancer cells including the liver. Supplementing the diet with creatine (Cr) has been suggested as a potential intervention to minimize DOX-induced side effects, but its effect in alleviating DOX-induced hepatoxicity is currently unknown. Therefore, we aimed to examine the effects of Cr supplementation on DOX-induced liver damage. Methods: Male Sprague-Dawley rats were fed a diet supplemented with 2% Cr for four weeks, 4% Cr for one week followed by 2% Cr for three more weeks, or control diet for four weeks. Animals then received either a bolus i.p. injection of DOX (15 mg/kg) or saline as a placebo. Animals were then sacrificed five days-post injection and markers of hepatoxicity were analyzed using the liver-to-body weight ratio, aspartate transaminase (AST)-to- alanine aminotransferase (ALT) ratio, alkaline phosphatase (ALP), lipemia, and T-Bilirubin. In addition, hematoxylin and eosin (H&E) staining, Picro-Sirius Red staining, and immunofluorescence staining for CD45, 8-OHdG, and β-galactosidase were performed to evaluate liver morphology, fibrosis, inflammation, oxidative stress, and cellular senescence, respectively. The mRNA levels for biomarkers of liver fibrosis, inflammation, oxidative stress, and senescence-related genes were measured in liver tissues. Chromosomal stability was evaluated using global DNA methylation ELISA. Results: The ALT/AST ratio and liver to body weight ratio tended to increase in the DOX group, and Cr supplementation tended to attenuate this increase. Furthermore, elevated levels of liver fibrosis, inflammation, oxidative stress, and senescence were observed with DOX treatment, and Cr supplementation prior to DOX treatment ameliorated this hepatoxicity. Moreover, DOX treatment resulted in chromosomal instability (i.e., altered DNA methylation profile), and Cr supplementation showed a tendency to restore chromosomal stability with DOX treatment. Conclusion: The data suggest that Cr protected against DOX-induced hepatotoxicity by attenuating fibrosis, inflammation, oxidative stress, and senescence.

scholarly journals Galangin Resolves Cardiometabolic Disorders through Modulation of AdipoR1, COX-2, and NF-κB Expression in Rats Fed a High-Fat Diet

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 769
Author(s):  
Patoomporn Prasatthong ◽  
Sariya Meephat ◽  
Siwayu Rattanakanokchai ◽  
Juthamas Khamseekaew ◽  
Sarawoot Bunbupha ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Tissue ◽  
Sprague Dawley ◽  
High Fat ◽  
Impaired Liver Function ◽  
Impaired Liver ◽  
Cardiometabolic Disorders ◽  
Cox 2 ◽  
Factor Α ◽  
And Oxidative Stress

Galangin is a natural flavonoid. In this study, we evaluated whether galangin could alleviate signs of metabolic syndrome (MS) and cardiac abnormalities in rats receiving a high-fat (HF) diet. Male Sprague–Dawley rats were given an HF diet plus 15% fructose for four months, and they were fed with galangin (25 or 50 mg/kg), metformin (100 mg/kg), or a vehicle for the last four weeks. The MS rats exhibited signs of MS, hypertrophy of adipocytes, impaired liver function, and cardiac dysfunction and remodeling. These abnormalities were alleviated by galangin (p < 0.05). Interleukin-6 and tumor necrosis factor-α concentrations and expression were high in the plasma and cardiac tissue in the MS rats, and these markers were suppressed by galangin (p < 0.05). These treatments also alleviated the low levels of adiponectin and oxidative stress induced by an HF diet in rats. The downregulation of adiponectin receptor 1 (AdipoR1) and cyclooxygenase-2 (COX-2) and the upregulation of nuclear factor kappa B (NF-κB) expression were recovered in the galangin-treated groups. Metformin produced similar effects to galangin. In conclusion, galangin reduced cardiometabolic disorders in MS rats. These effects might be linked to the suppression of inflammation and oxidative stress and the restoration of AdipoR1, COX-2, and NF-κB expression.

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