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Neural Regeneration Research Apr 2021Batroxobin is a thrombin-like serine protease from the venom of the Bothrops atrox and Bothrops moojeni snake species. Sirtuin 1 (Sirt1) has been shown to play an...
Batroxobin is a thrombin-like serine protease from the venom of the Bothrops atrox and Bothrops moojeni snake species. Sirtuin 1 (Sirt1) has been shown to play an important role in neuroprotection after traumatic brain injury. However, its underlying mechanism of action remains poorly understood. The purpose of this study was to investigate whether the mechanism by which batroxobin participates in the activation of astrocytes is associated with Sirt1. Mouse models of nigrostriatal pathway injury were established. Immediately after modeling, mice were intraperitoneally administered 39 U/kg batroxobin. Batroxobin significantly reduced the expression of cleaved caspase-3 in both the substantia nigra and striatum, inhibited neuronal apoptosis, and promoted the recovery of rat locomotor function. These changes coincided with a remarkable reduction in astrocyte activation. Batroxobin also reduced Sirt1 expression and extracellular signal-regulated kinase activation in brain tissue. Intraperitoneal administration of the Sirt1-specific inhibitor EX527 (5 mg/kg) 30 minutes prior to injury could inhibit the abovementioned effects. In mouse astrocyte cultures, 1 ng/mL batroxobin attenuated interleukin-1β-induced activation of astrocytes and extracellular signal-regulated kinase. EX527 could also inhibit the effects of batroxobin. These findings suggest that batroxobin inhibits astrocyte activation after nigrostriatal pathway injury through the Sirt1 pathway. This study was approved by the Animal Ethics Committee of China Medical University, China (approval No. CMU2020037) on July 19, 2015.
PubMed: 33063734
DOI: 10.4103/1673-5374.295343 -
Blood Coagulation & Fibrinolysis : An... Mar 2009The objective of the present study was to evaluate the effect of batroxobin agents on perioperative hemorrhage in thoracic surgery.We systematically searched Cochrane... (Meta-Analysis)
Meta-Analysis Review
The objective of the present study was to evaluate the effect of batroxobin agents on perioperative hemorrhage in thoracic surgery.We systematically searched Cochrane Library, Pubmed, EMBASE and the China Biological Medicine CD-ROM Databases up to August 2007. Reference lists of all included studies and of reviews related to the topic of the present systematic review were manually searched. Two reviewers independently identified the eligible studies, assessed their methodological quality and extracted data. Results of relevant outcomes were pooled together whenever possible, using RevMan software.Five randomized controlled trials involving 678 patients were included. Three trials were for pneumonectomy and two for cardiac surgery with cardiopulmonary bypass. The quality of the identified studies was generally poor. All the trials claimed randomized allocation, but allocation concealment was unclear. Blinding was not mentioned. Two trials found that batroxobin agents decreased intraoperative blood loss for pneumonectomy. Mean differences between the batroxobin agents group and the no-treatment group were -182.20 ml [95% confidence interval (CI), -207.48 to -156.92] and -131.32 ml (95% CI, -142.95 to -119.69), respectively, for these two trials. All included trials reported less drainage volume favoring the batroxobin agents group. Mean differences at different time points after operation ranged from -15 ml (95% CI, -31.77 to 1.77) to -150.60 ml (95% CI, -179.26 to -121.94). Although most of the differences between the batroxobin agents group and the no treatment group were statistically significant, clinical value was limited.There is not enough evidence supporting any benefit of batroxobin agents for hemorrhage during thoracic surgery.
Topics: Batroxobin; Blood Loss, Surgical; Fibrinolytic Agents; Humans; Randomized Controlled Trials as Topic; Thoracic Surgical Procedures
PubMed: 19786937
DOI: 10.1097/MBC.0b013e3283254532 -
Thrombosis Research Oct 1985The B. moojeni thrombic protease, batroxobin, was acylated by 4-amidinophenyl benzoate at the active site serine hydroxyl. From the enzymatically inactive...
The B. moojeni thrombic protease, batroxobin, was acylated by 4-amidinophenyl benzoate at the active site serine hydroxyl. From the enzymatically inactive benzoyl-batroxobin, batroxobin is generated with a half-life of deacylation of about one hour. The clotting activity of benzoyl-batroxobin in plasma is recovered with deacylation. The effects of batroxobin and benzoyl-batroxobin were studied following intravenous injection in rats. Compared to defibrinogenation with batroxobin, that obtained with benzoyl-batroxobin was much retarded. Batroxobin caused microthrombosis initially, which did not develop upon injection of benzoyl-batroxobin in equivalent doses.
Topics: Acylation; Batroxobin; Binding Sites; Blood Coagulation; Elapid Venoms; Fibrinogen; Half-Life; Humans; Kinetics; Peptide Hydrolases
PubMed: 3911486
DOI: 10.1016/0049-3848(85)90348-2 -
Current Medicinal Chemistry 2017Snakes are fascinating creatures and have been residents of this planet well before ancient humans dwelled the earth. Venomous snakes have been a figure of fear, and... (Review)
Review
Snakes are fascinating creatures and have been residents of this planet well before ancient humans dwelled the earth. Venomous snakes have been a figure of fear, and cause notable mortality throughout the world. The venom constitutes families of proteins and peptides with various isoforms that make it a cocktail of diverse molecules. These biomolecules are responsible for the disturbance in fundamental physiological systems of the envenomed victim, leading to morbidity which can lead to death if left untreated. Researchers have turned these life-threatening toxins into life-saving therapeutics via technological advancements. Since the development of captopril, the first drug that was derived from bradykininpotentiating peptide of Bothrops jararaca, to the disintegrins that have potent activity against certain types of cancers, snake venom components have shown great potential for the development of lead compounds for new drugs. There is a continuous development of new drugs from snake venom for coagulopathy and hemostasis to anti-cancer agents. In this review, we have focused on different snake venom proteins / peptides derived drugs that are in clinical use or in developmental stages till to date. Also, some commonly used snake venom derived diagnostic tools along with the recent updates in this exciting field are discussed.
Topics: Animals; Anticoagulants; Batroxobin; Blood Coagulation; Captopril; Peptides; Snake Venoms; Snakes; Thrombosis; Tirofiban; Toxins, Biological; Tyrosine
PubMed: 28578650
DOI: 10.2174/0929867324666170605091546 -
CNS Neuroscience & Therapeutics May 2019The objective of this study was to evaluate cerebral venous recanalization with magnetic resonance black-blood thrombus imaging (MRBTI) in patients with cerebral venous...
AIMS
The objective of this study was to evaluate cerebral venous recanalization with magnetic resonance black-blood thrombus imaging (MRBTI) in patients with cerebral venous thrombosis (CVT) who underwent batroxobin treatment in combination with anticoagulation.
METHODS
A total of 31 CVT patients were enrolled in this real-world registry study. The patients were divided into batroxobin (n = 21) and control groups (n = 10). In addition to the same standard anticoagulation as in the control group, patients in the batroxobin group underwent intravenous batroxobin for a total of three times.
RESULTS
In the batroxobin group compared with the control group, we found better odds of recanalization degree [adjusted OR (95%CI) of 8.10 (1.61-40.7)] and segment-stenosis attenuation [adjusted OR (95%CI) of 4.48 (1.69-11.9)] with batroxobin treatment. We further noted a higher ratio of patients with the attenuation of stenosis [adjusted OR (95%CI) of 26.4 (1.10-635)]; as well as a higher ratio of segments with stenosis reversion [adjusted OR (95%CI) of 4.52 (1.48-13.8)]. However, neurological deficits between the two groups showed no statistical difference at 90-day follow-up (P > 0.05).
CONCLUSIONS
Batroxobin may promote venous sinus recanalization and attenuate CVT-induced stenosis. Further randomized study of this promising drug may be warranted to better delineate the amount of benefit.
Topics: Adult; Anticoagulants; Batroxobin; Constriction, Pathologic; Drug Therapy, Combination; Female; Fibrinolytic Agents; Humans; Intracranial Thrombosis; Magnetic Resonance Imaging; Male; Registries; Treatment Outcome; Venous Thrombosis
PubMed: 30675757
DOI: 10.1111/cns.13093 -
PloS One 2019Batroxobin, isolated from Bothrops moojeni, is a defibrinogenating agent used as a thrombin-like serine protease against fibrinogen for improving microcirculation. Here,...
Batroxobin, isolated from Bothrops moojeni, is a defibrinogenating agent used as a thrombin-like serine protease against fibrinogen for improving microcirculation. Here, we investigated whether, and if so, how batroxobin restores ischemic tissue injury in terms of anti-inflammatory effects. In an in vitro flow cytometry assay for human neutrophil extracellular traps (NETs), batroxobin (DF-521; Defibrase) inhibited human NETs induced by tumor necrosis factor-α (TNF-α) in the presence of human fibrinogen. Next, the effect of batroxobin was investigated by immunohistochemistry of the anterior tibial muscle (ATM) in an ischemic hindlimb model using C57BL/6J mice intraperitoneally injected with DF-521 versus the saline control. NETs and fibrinogen deposition in the ischemic ATM decreased in DF-521-treated mice on day 2 after ischemia. Meanwhile, reverse transcription-quantitative PCR assay of the ischemic ATM unveiled continuous downregulation in the expression of the genes; Tnf-α and nitric oxide synthase2 (Nos2) with hypoxia-inducible factor-1α (Hif-1α) and vascular endothelial growth factor-a (Vegf-a) from day 3 to day 7, but the upregulation of arginase-1 (Arg-1) and placental growth factor (Plgf) with myogenin (Myog) on day 7. Daily intraperitoneal DF-521 injection for the initial 7 days into mice with ischemic hindlimbs promoted angiogenesis and arteriogenesis on day 14. Moreover, DF-521 injection accelerated myofiber maturation after day 14. Laser doppler imaging analysis revealed that blood perfusion in DF-521-injected mice significantly improved on day 14 versus the saline control. Thus, DF-521 improves microcirculation by protecting NETs with tissue defibrinogenation, thereby protecting against severe ischemic tissue injury and accelerating vascular and skeletal muscular regeneration. To our knowledge, batroxobin might be the first clinically applicable NET inhibitor against ischemic diseases.
Topics: Adult; Animals; Anti-Inflammatory Agents; Batroxobin; Cells, Cultured; Disease Models, Animal; Extracellular Traps; Fibrinolytic Agents; Hindlimb; Humans; Inflammation; Ischemia; Male; Mice, Inbred C57BL; Middle Aged; Wound Healing; Young Adult
PubMed: 31419236
DOI: 10.1371/journal.pone.0220898 -
The Journal of Laryngology and Otology Mar 2024To investigate the effects of combination therapy with and without batroxobin, and the frequency of batroxobin use on the prognosis of profound sudden sensorineural...
OBJECTIVE
To investigate the effects of combination therapy with and without batroxobin, and the frequency of batroxobin use on the prognosis of profound sudden sensorineural hearing loss.
METHODS
Hearing recovery in the batroxobin group (231 patients) and non-batroxobin group (56 patients) was compared. The correlation between the number of times batroxobin was used and hearing recovery was analysed.
RESULTS
The decrease in hearing threshold and overall improvement rate in the batroxobin group with hearing loss exceeding 100 dB HL was significantly higher than that in the non-batroxobin group. There was no linear correlation between the number of times batroxobin was used and the overall improvement rate. Using batroxobin two to three times achieved a therapeutic effectiveness plateau.
CONCLUSION
Batroxobin can improve the efficacy of combination therapy for profound sudden sensorineural hearing loss exceeding 100 dB HL, and using batroxobin two to three times yields the maximum overall improvement rate.
Topics: Humans; Batroxobin; Treatment Outcome; Hearing Loss, Sudden; Hearing Loss, Sensorineural; Hearing
PubMed: 37994420
DOI: 10.1017/S0022215123001512 -
International Immunopharmacology Jul 2019Batroxobin is a medicinal preparation extracted from the venom of the Fer-de-Lance snake, and is used to lower blood viscosity, promote blood fibrinogen decomposition,...
OBJECTIVE
Batroxobin is a medicinal preparation extracted from the venom of the Fer-de-Lance snake, and is used to lower blood viscosity, promote blood fibrinogen decomposition, and inhibit thrombosis. This research is to investigate whether batroxobin can improve the survival of random skin flaps in a rat model.
MATERIALS AND METHODS
Dorsal McFarlane flaps were harvested from 36 rats divided into two groups. Experimental group: Batroxobin was administered via the tail vein once daily.
CONTROL GROUP
The same amount of normal saline was injected instead. On day 2, superoxide dismutase (SOD) and malondialdehyde (MDA) levels were measured. On day 7, tissue slices were stained with haematoxylin and eosin. Expression of vascular endothelial growth factor (VEGF) was immunohistochemically evaluated. Microcirculatory flow was measured by laser Doppler flowmetry. Flap angiography, using the lead oxide-gelatin injection technique, was performed with the aid of a soft X-ray machine.
RESULTS
The batroxobin group exhibited a greater mean flap survival area, a better microcirculatory flow, and higher-level expression of SOD and VEGF compared with the control group. However, the MDA level was significantly reduced.
CONCLUSION
Batroxobin effectively improved the survival of random skin flaps.
Topics: Animals; Batroxobin; Male; Malondialdehyde; Microcirculation; Neovascularization, Physiologic; Rats, Sprague-Dawley; Superoxide Dismutase; Surgical Flaps; Vascular Endothelial Growth Factor A
PubMed: 31003000
DOI: 10.1016/j.intimp.2019.04.011 -
Frontiers in Neurology 2022
PubMed: 36212651
DOI: 10.3389/fneur.2022.1021547 -
Brain Research Bulletin Oct 2016Traumatic brain injury triggers a series of damaged processes, such as neuronal death and apoptosis, inflammation and scar formation, which contribute to evolution of...
Traumatic brain injury triggers a series of damaged processes, such as neuronal death and apoptosis, inflammation and scar formation, which contribute to evolution of brain injury. The present study investigated the neuroprotective effects of batroxobin, a drug widely used clinically for ischemia, in a nigrostriatal pathway injury model. Mice subjected to the nigrostriatal pathway injury were injected with batroxobin (30 BU/kg) or vehicle immediately after injury. The behavioral studies showed that batroxobin could improve the motor function in injured mice in long term. Batroxobin also reduced neuronal apoptosis and inflammation at the acute stage. Moreover, administration of batroxobin attenuated the scar formation and reduced the lesion size at 4 and 14days after brain injury. These results suggest that batroxobin has beneficial effects on the nigrostriatal pathway injury, indicating a potential clinical application.
Topics: Animals; Apoptosis; Batroxobin; Cicatrix; Corpus Striatum; Disease Models, Animal; Male; Mice; Motor Activity; Neural Pathways; Neuroprotective Agents; Random Allocation; Substantia Nigra
PubMed: 27679398
DOI: 10.1016/j.brainresbull.2016.09.014