ベンゾニダゾール

ANone: Although the precise mechanism remains unclear, Benznidazole's activity is believed to stem from its reductive metabolism within the parasite, Trypanosoma cruzi. This process generates reactive metabolites that cause significant damage to parasite DNA, potentially triggering DNA damage response pathways and inhibiting parasite replication. [, , , ]

ANone: Benznidazole treatment leads to widespread DNA damage in T. cruzi. [, ] This can induce a transient non-replicative state in the surviving intracellular amastigotes, likely as part of the parasite's attempt at DNA repair. [] Additionally, Benznidazole treatment can affect the expression of various proteins in T. cruzi, including those involved in transcription, protein destination, and oxidative stress responses. [, ]

ANone: Benznidazole's molecular formula is C₁₂H₁₂N₄O₃, and its molecular weight is 260.25 g/mol. []

ANone: Yes, studies have investigated the electrochemical reduction of Benznidazole using techniques like cyclic voltammetry with DNA-electrochemical biosensors. These studies revealed details about the reduction mechanism, highlighting the formation of a hydroxylamine derivative as a potentially cytotoxic species. []

ANone: Studies show that Benznidazole demonstrates good compatibility with most pharmaceutical excipients, showing thermal incompatibility only with polyethylene glycol. []

ANone: While Benznidazole is primarily known for its antiparasitic activity, its mechanism of action does not involve direct catalytic properties. Its efficacy is linked to its metabolic activation within the parasite, leading to the formation of reactive species that damage parasite DNA. [, , , ]

ANone: While computational studies specific to Benznidazole's mechanism are limited in the provided research, the identification of specific protein alterations in resistant strains, like overexpression of mitochondrial superoxide dismutase and tryparedoxin-1, could offer potential targets for computational modeling and drug design efforts in the future. []

ANone: Research highlights the development of several nanoformulations, such as nanostructured lipid carriers, solid lipid nanoparticles, liposomes, quatsomes, and cyclodextrins, to enhance Benznidazole's therapeutic profile. These approaches aim to improve solubility, bioavailability, and potentially reduce toxicity. [, ]

ANone: Yes, in vitro studies suggest that cyclodextrin-Benznidazole complexes exhibit significantly lower cytotoxicity compared to free Benznidazole, while maintaining comparable trypanocidal activity. This finding highlights the potential of cyclodextrin-based formulations for improving the safety profile of Benznidazole treatment. []

ANone: While the provided research doesn't offer detailed safety protocols, standard procedures for handling potentially hazardous substances should be followed. This includes using appropriate personal protective equipment, ensuring adequate ventilation, and following established waste disposal regulations. Further consultation with relevant safety data sheets and guidelines is recommended.

ANone: Studies in mice chronically infected with the Berenice-78 strain of T. cruzi showed altered Benznidazole pharmacokinetics compared to healthy mice. This includes increased absorption rate, volume of distribution, and clearance, along with reduced time to reach maximum serum concentration and absorption half-life. These changes suggest potential influences of chronic inflammation on drug absorption and distribution. []

ANone: Yes, research indicates that chronic T. cruzi infection in mice leads to longer and higher Benznidazole exposure in the colon and heart. Additionally, tissue penetration ratios (AUCtissue/AUCserum) were significantly increased in the brain, colon, and heart of infected mice, suggesting altered drug distribution patterns. []

ANone: Research using a mouse model of chronic Chagas disease demonstrated that Benznidazole treatment led to a decrease in both cardiac parasitism and myocarditis compared to untreated infected mice. Additionally, treated mice showed reduced cardiac conduction disturbances, suggesting a protective effect of the drug on cardiac function. []

ANone: Studies utilizing bioluminescent imaging showed that early initiation of Benznidazole treatment during acute T. cruzi infection in mice resulted in complete parasite clearance, while delayed treatment initiation led to parasite persistence despite exhibiting initial efficacy. This highlights the importance of early diagnosis and treatment for optimal outcomes. []

ANone: Research shows that Benznidazole treatment in chronically infected mice can modulate the immune response against T. cruzi. This includes a reduction in antibody levels against various parasite antigens, as well as a decrease in antibodies against cardiac receptors, suggesting a potential benefit in mitigating autoimmune responses associated with Chagasic cardiomyopathy. []

ANone: Benznidazole resistance in T. cruzi is a significant concern. Studies have identified T. cruzi strains with varying levels of susceptibility to Benznidazole. This variability appears to be linked to several factors, including the parasite's genetic background and alterations in specific proteins involved in drug metabolism and oxidative stress response. [, , , ]

ANone: Yes, studies have identified T. cruzi strains exhibiting resistance to both Benznidazole and Nifurtimox, the two main drugs used for Chagas disease treatment. This cross-resistance poses a significant challenge for disease management and highlights the urgent need for new therapeutic options. [, , ]

ANone: Yes, research has identified T. cruzi strains resistant to Benznidazole, Nifurtimox, and conventional antifungal azoles like ketoconazole. This highlights the challenge of treating infections with multidrug-resistant strains and emphasizes the need for novel therapeutic strategies. []

ANone: Benznidazole treatment is known to cause a range of adverse events, with hypersensitivity reactions being the most common. These reactions can manifest as skin rashes, itching, and other allergic symptoms. Other reported side effects include headache, gastrointestinal disturbances, and neurological symptoms. [, , ]

ANone: Yes, studies suggest that female patients are more prone to experiencing adverse events, particularly hypersensitivity reactions, compared to male patients. Additionally, the specific type of Benznidazole formulation used may also influence the risk of certain adverse events. []

ANone: Nanoformulations, such as those encapsulated in lipid nanoparticles or cyclodextrins, offer several potential advantages over conventional Benznidazole formulations. These include improved drug solubility and bioavailability, enhanced drug stability, and potentially reduced toxicity by enabling targeted drug delivery and controlled drug release. [, ]

ANone: Yes, research has investigated the use of nanoformulated Benznidazole administered through different regimens, including continuous daily dosing and intermittent dosing (once every 7 days). Both approaches demonstrated promising outcomes in a chronic mouse model of T. cruzi infection, including parasite clearance, reduced tissue damage, and improved cardiac function. Importantly, the intermittent dosing regimen achieved these results with a lower total drug dose, highlighting its potential for improved therapeutic index. []

ANone: While the provided research does not focus on specific biomarkers for monitoring Benznidazole treatment response, studies highlight the importance of PCR-based methods for detecting parasite DNA in blood and tissues. These methods offer greater sensitivity compared to traditional parasitological methods and can help assess treatment efficacy more accurately. [, , ]

ANone: High-performance liquid chromatography (HPLC) coupled with diode array detection is a widely used technique for quantifying Benznidazole concentrations in biological samples like serum and tissues. This method offers high sensitivity and selectivity for accurate drug monitoring. [, ]