Novel Toxicodynamic Model of Subcutaneous Envenomation to Characterize Snake Venom Coagulopathies and Assess the Efficacy of Site-Directed Inorganic Antivenoms.

Article

作者: Nielsen, Vance G

Venomous snake bite adversely affects millions of people yearly, but few animal models allow for the determination of toxicodynamic timelines with hemotoxic venoms to characterize the onset and severity of coagulopathy or assess novel, site-directed antivenom strategies. Thus, the goals of this investigation were to create a rabbit model of subcutaneous envenomation to assess venom toxicodynamics and efficacy of ruthenium-based antivenom administration. New Zealand White rabbits were sedated with midazolam via the ear vein and had viscoelastic measurements of whole blood and/or plasmatic coagulation kinetics obtained from ear artery samples. Venoms derived from Crotalus scutulatus scutulatus, Bothrops moojeni, or Calloselasma rhodostoma were injected subcutaneously, and changes in coagulation were determined over three hours and compared to samples obtained prior to envenomation. Other rabbits had ruthenium-based antivenoms injected five minutes after venom injection. Viscoelastic analyses demonstrated diverse toxicodynamic patterns of coagulopathy consistent with the molecular composition of the proteomes of the venoms tested. The antivenoms tested attenuated venom-mediated coagulopathy. A novel rabbit model can be used to characterize the onset and severity of envenomation by diverse proteomes and to assess site-directed antivenoms. Future investigation is planned involving other medically important venoms and antivenom development.

2022-06-01·DARU Journal of Pharmaceutical Sciences

Cobalt (III) complex exerts anti-cancer effects on T cell lymphoma through induction of cell cycle arrest and promotion of apoptosis

Article

作者: Gond, Mannu Kumar ; Bharty, Manoj Kumar ; Acharya, Arbind ; Singh, Rishi Kant ; Verma, Praveen Kumar ; Kumar, Sandeep ; Kumar, Sanjay ; Shukla, Alok

PURPOSECobalt-based compounds are emerging as a non-platinum-based anti-cancer effective therapeutic agent. However, there is a limited study regarding the therapeutic efficacy of Cobalt-based drugs against Non-Hodgkin's Lymphoma (NHLs) such as T cell lymphoma. Therefore, in the present study we investigated the anti-tumor role of cobalt(III) complex [Co(ptsm)NH₃(o-phen)]·CH₃OH on Dalton's Lymphoma (DL) cells.MATERIALS AND METHODSCytotoxicity of the cobalt complex was estimated by MTT assay. Analysis of mitochondrial membrane potential, cell cycle and Reactive oxygen species (ROS) generation, and Annexin V/PI staining was done by Flow cytometry, while AO/EtBr staining by fluorescence microscopy in cobalt complex treated DL cell. Expression of cell cycle and apoptosis regulatory protein was analyzed by Western blotting. In addition, in vivo study of the cobalt complex was evaluated in well-established DL bearing mice by monitoring physiological parameters and mean survival time.RESULTSOur study showed that cobalt complex triggered apoptosis and induced cell cycle arrest in DL cells. Furthermore, this also decreased mitochondrial membrane potential and increased intracellular ROS generation in cancer cells. In addition, changed expression of cell cycle and apoptosis regulatory protein was found with enhanced activity of caspase-3 and 9 in the treated cells. Additionally, administration of cobalt complex showed a significant increase in the survivability of tumor-bearing host, which was accomplished by decreasing physiological parameters.CONCLUSIONTaken together, these data revealed anti-tumor potential of cobalt complex against DL cells through cell cycle arrest and mitochondrial-dependent apoptosis. Henceforth, cobalt-based drugs could be a new generation therapeutic drug to treat hematological malignancies.

2022-01-01·The Journal of Pharmacology and Experimental Therapeutics

The Role of Ruthenium Compounds in Neurologic Diseases: A Minireview

Review

作者: de Sá Roriz Caminha, Juan ; Gonzaga de França Lopes, Luiz ; Barreto Oriá, Reinaldo ; Belayev, Ludmila ; Gama Justi, Fátima Virgínia ; Rodrigues Roque, Cássia ; Muniz Carvalho, Edinilton ; Araújo Matos, Gabriella ; Soares Campelo, Márcio Wilker

Ruthenium compounds, nitric oxide donors in biologic systems, have emerged as a promising therapeutic alternative to conventional drugs in anticancer chemotherapy and as a potential neuroprotective agent with fewer cytotoxic effects. This minireview summarizes promising studies with ruthenium complexes and their roles in cancer, neuroinflammation, neurovascular, and neurodegenerative diseases. The up-to-date evidence supports that ruthenium-based compounds have beneficial effects against gliomas and other types of brain cancers, reduce motor symptoms in models of cerebral ischemia-reperfusion, and may act in the control of nociceptive and inflammatory events, such as those seen in early Alzheimer's disease. More studies are needed to fill many current knowledge gaps about the intricate and complex biologic effects and therapeutic-related mechanisms of ruthenium, stimulating further research. SIGNIFICANCE STATEMENT: This minireview summarizes studies addressing the role of ruthenium compounds on neurological illnesses, focusing on brain cancer and neurovascular and neurodegenerative diseases. No such review is available in the literature.

100 项与 AL-1834 相关的药物交易

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