Anhydroecgonine methyl ester, a cocaine pyrolysis product, contributes to cocaine-induced rat primary hippocampal neuronal death in a synergistic and time-dependent manner

Udo, Mariana Sayuri Berto; Silva, Mariana Aguilera Alencar da; Prates, Sara de Souza; Dal'Jovem, Leandro Ferreira; Duro, Stephanie de Oliveira; Faião-Flores, Fernanda; Garcia, Raphael Caio Tamborelli; Maria-Engler, Silvya Stuchi; Marcourakis, Tânia

doi:10.1007/s00204-021-03017-z

Cited by 7 publications

(3 citation statements)

References 53 publications

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“…In addition, being a metachromatic dye, acridine orange stains DNA green and RNA orange under appropriate conditions. However, EB imparts red/dark orange fluorescence when there is an altercation in cell membranes by intercalating inside the DNA [ 40 ]. Here, all the test samples were resuspended in 25 µL of a dye blend, formed by adding 100 µg/mL of each (AO/EB) dye in PBS (1 mL).…”

Section: Methodsmentioning

confidence: 99%

Neuroprotective Ability of Apocynin Loaded Nanoparticles (APO-NPs) as NADPH Oxidase (NOX)-Mediated ROS Modulator for Hydrogen Peroxide-Induced Oxidative Neuronal Injuries

et al. 2021

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Apocynin (APO) is a known multi-enzymatic complexed compound, employed as a viable NADPH oxidase (NOX) inhibitor, extensively used in both traditional and modern-day therapeutic strategies to combat neuronal disorders. However, its therapeutic efficacy is limited by lower solubility and lesser bioavailability; thus, a suitable nanocarrier system to overcome such limitations is needed. The present study is designed to fabricate APO-loaded polymeric nanoparticles (APO-NPs) to enhance its therapeutic efficacy and sustainability in the biological system. The optimized APO NPs in the study exhibited 103.6 ± 6.8 nm and −13.7 ± 0.43 mV of particle size and zeta potential, respectively, along with further confirmation by TEM. In addition, the antioxidant (AO) abilities quantified by DPPH and nitric oxide scavenging assays exhibited comparatively higher AO potential of APO-NPs than APO alone. An in-vitro release profile displayed a linear diffusion pattern of zero order kinetics for APO from the NPs, followed by its cytotoxicity evaluation on the PC12 cell line, which revealed minimal toxicity with higher cell viability, even after treatment with a stress inducer (H2O2). The stability of APO-NPs after six months showed minimal AO decline in comparison to APO only, indicating that the designed nano-formulation enhanced therapeutic efficacy for modulating NOX-mediated ROS generation.

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Section: Methodsmentioning

confidence: 99%

Neuroprotective Ability of Apocynin Loaded Nanoparticles (APO-NPs) as NADPH Oxidase (NOX)-Mediated ROS Modulator for Hydrogen Peroxide-Induced Oxidative Neuronal Injuries

et al. 2021

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“…Cunha-Oliveira et al saw that 1 mM of cocaine led to an increase in calcium concentrations and caspase-3 activity, as well as a decrease in mitochondrial membrane potential and ATP in rat cortical neurons exposed for 24 h [112]. Furthermore, cocaine exposure in models of rat primary hippocampal neurons (1 mM) and mouse primary cortical neurons (1, 10, 100 and 200 µM) increased the expression of autophagy markers LC-3 I and II [113,114]. Nifedipine, a selective blocker of L-type calcium channels, reverted the reduction of cerebral blood flow and tissue oxygenation induced by increases in neuronal calcium currents, in the prefrontal cortex of rats exposed to 1 mg/Kg cocaine [115].…”

Section: Brainmentioning

confidence: 98%

Cocaine: An Updated Overview on Chemistry, Detection, Biokinetics, and Pharmacotoxicological Aspects including Abuse Pattern

Bravo

Faria

Brito-da-Costa

et al. 2022

Toxins

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Cocaine is one of the most consumed stimulants throughout the world, as official sources report. It is a naturally occurring sympathomimetic tropane alkaloid derived from the leaves of Erythroxylon coca, which has been used by South American locals for millennia. Cocaine can usually be found in two forms, cocaine hydrochloride, a white powder, or ‘crack’ cocaine, the free base. While the first is commonly administered by insufflation (‘snorting’) or intravenously, the second is adapted for inhalation (smoking). Cocaine can exert local anaesthetic action by inhibiting voltage-gated sodium channels, thus halting electrical impulse propagation; cocaine also impacts neurotransmission by hindering monoamine reuptake, particularly dopamine, from the synaptic cleft. The excess of available dopamine for postsynaptic activation mediates the pleasurable effects reported by users and contributes to the addictive potential and toxic effects of the drug. Cocaine is metabolised (mostly hepatically) into two main metabolites, ecgonine methyl ester and benzoylecgonine. Other metabolites include, for example, norcocaine and cocaethylene, both displaying pharmacological action, and the last one constituting a biomarker for co-consumption of cocaine with alcohol. This review provides a brief overview of cocaine’s prevalence and patterns of use, its physical-chemical properties and methods for analysis, pharmacokinetics, pharmacodynamics, and multi-level toxicity.

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“…Additionally, CBD has shown the ability to inhibit glial cell activation in models of neurodegenerative diseases and psychosis (Campos et al., 2016; Cassano et al., 2020; Lisboa et al., 2016; Martín‐Moreno et al., 2011; Milano & Capasso, 2018). This is interesting and should be highlighted positively, considering that cocaine is known to be neurotoxic and to induce autophagy (Guha et al., 2016; Mai et al., 2019; Udo et al., 2021), and to be strongly related to the development of acute psychosis (Inchausti et al., 2020; Sabe et al., 2021).…”

Section: Introductionmentioning

confidence: 99%

Impact of cannabidiol on brain glucose metabolism of C57Bl/6 male mice previously exposed to cocaine

Spelta,

Real,

Bruno

et al. 2024

J of Neuroscience Research

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Despite evidence of the beneficial effects of cannabidiol (CBD) in animal models of cocaine use disorder (CUD), CBD neuronal mechanisms remain poorly understood. This study investigated the effects of CBD treatment on brain glucose metabolism, in a CUD animal model, using [18F]FDG positron emission tomography (PET). Male C57Bl/6 mice were injected with cocaine (20 mg/kg, i.p.) every other day for 9 days, followed by 8 days of CBD administration (30 mg/kg, i.p.). After 48 h, animals were challenged with cocaine. Control animals received saline/vehicle. [18F]FDG PET was performed at four time points: baseline, last day of sensitization, last day of withdrawal/CBD treatment, and challenge. Subsequently, the animals were euthanized and immunohistochemistry was performed on the hippocampus and amygdala to assess the CB1 receptors, neuronal nuclear protein, microglia (Iba1), and astrocytes (GFAP). Results showed that cocaine administration increased [18F]FDG uptake following sensitization. CBD treatment also increased [18F]FDG uptake in both saline and cocaine groups. However, animals that were sensitized and challenged with cocaine, and those receiving only an acute cocaine injection during the challenge phase, did not exhibit increased [18F]FDG uptake when treated with CBD. Furthermore, CBD induced modifications in the integrated density of NeuN, Iba, GFAP, and CB1R in the hippocampus and amygdala. This is the first study addressing the impact of CBD on brain glucose metabolism in a preclinical model of CUD using PET. Our findings suggest that CBD disrupts cocaine‐induced changes in brain energy consumption and activity, which might be correlated with alterations in neuronal and glial function.

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Anhydroecgonine methyl ester, a cocaine pyrolysis product, contributes to cocaine-induced rat primary hippocampal neuronal death in a synergistic and time-dependent manner

Cited by 7 publications

References 53 publications

Neuroprotective Ability of Apocynin Loaded Nanoparticles (APO-NPs) as NADPH Oxidase (NOX)-Mediated ROS Modulator for Hydrogen Peroxide-Induced Oxidative Neuronal Injuries

Neuroprotective Ability of Apocynin Loaded Nanoparticles (APO-NPs) as NADPH Oxidase (NOX)-Mediated ROS Modulator for Hydrogen Peroxide-Induced Oxidative Neuronal Injuries

Cocaine: An Updated Overview on Chemistry, Detection, Biokinetics, and Pharmacotoxicological Aspects including Abuse Pattern

Impact of cannabidiol on brain glucose metabolism of C57Bl/6 male mice previously exposed to cocaine

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