Preventive effects of fructose and N‐acetyl‐<scp>L</scp>‐cysteine against cytotoxicity induced by the psychoactive compounds N‐methyl‐5‐(2‐aminopropyl)benzofuran and 3,4‐methylenedioxy‐N‐methamphetamine in isolated rat hepatocytes

Nakagawa, Yoshio; Suzuki, Tomohiko; Inomata, Akiko

doi:10.1002/jat.3523

Cited by 6 publications

(7 citation statements)

References 39 publications

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“…The mechanism of fructose protective effects might be that fructose slows down adenosine triphosphate (ATP) depletion caused by the drug treatments. 17 The relatively high cellular ATP levels compared with non-fructose treatment ameliorated the SANPAs cytotoxicity toward mammalian cells. 17 Although the performance for SANPAs was not ideal, it still exhibited higher inhibitory effects on bacteria than hFOB and HDF cells.…”

Section: In Vitro Cytotoxicitymentioning

confidence: 99%

Short Communication: Fructose-Enhanced Antibacterial Activity of Self-Assembled Nano-Peptide Amphiphiles for Treating Antibiotic-Resistant Bacteria

Gao

Chang

Wang

et al. 2020

IJN

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Background: In recent years, numerous bacteria have become resistant to conventional antibiotics. Fortunately, an increasing body of research indicates that through the addition of specific metabolites (like sugars), the antibacterial activity of certain drugs can be enhanced. A new type of self-assembled nano-peptide amphiphile (SANPA) was designed in this study to treat antibiotic-resistant bacterial infections and to reduce the use of antibiotics. Methods: Here, SANPAs were self-assembled into nanorod structures with a diameter of ca. 10.5 nm at concentrations greater than the critical micelle concentration (CMC) of 44.67 μM. Both Gram-positive and Gram-negative bacteria were treated with SANPAs with fructose supplementation. Results: After a 30-min fructose pre-incubation, SANPAs reduced bacteria growth relative to non-fructose treatments at all concentrations. Cytotoxicity assays indicated that the presence of fructose seemed to slightly ameliorate the cytotoxic effect of the treatment on model human fetal osteoblasts (or bone-forming cells) and human dermal fibroblasts. Conclusion: We demonstrated here that SANPAs-like nanomaterials have a promising potential to treat antibiotic-resistant bacteria, especially when added to fructose, potentially limiting their associated infections.

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Section: In Vitro Cytotoxicitymentioning

confidence: 99%

Short Communication: Fructose-Enhanced Antibacterial Activity of Self-Assembled Nano-Peptide Amphiphiles for Treating Antibiotic-Resistant Bacteria

Gao

Chang

Wang

et al. 2020

IJN

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“…On the other hand, rat hepatocytes were preincubated with NAC at a concentration of 5.0 mM for 15 minutes before the addition of photoinitiators. The concentrations of NAC and fructose used in this study were referred to the ranges in previous studies (Cannon, Harvison, & Rush, 1991;Nakagawa et al, 2014;Nakagawa, Suzuki, & Inomata, 2018). Corresponding control groups received an equivalent volume of DMSO.…”

Section: Isolation and Cell Culture Incubation Of Hepatocytesmentioning

confidence: 99%

Cytotoxic effects of thioxanthone derivatives as photoinitiators on isolated rat hepatocytes

Nakagawa

Inomata

Moriyasu

et al. 2019

J of Applied Toxicology

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Thioxanthone and its analogues, 2-or 4-isopropylthioxanthone, 2-chlorothioxanthone, 2,4-diethylthioxanthone (DETX) and xanthone, are used as photoinitiators of ultraviolet (UV) light-initiated curable inks. As these photoinitiators were found in numerous food/beverage products packaged in cartons printed with UV-cured inks, the cytotoxic effects and mechanisms of these compounds were studied in freshly isolated rat hepatocytes. The toxicity of DETX was greater than that of other compounds. DETX elicited not only concentration (0-2.0 mM)-and time (0-3 hours)-dependent cell death accompanied by the depletion of cellular adenosine triphosphate (ATP), and reduced glutathione (GSH) and protein thiol levels, but also the accumulation of GSH disulfide and malondialdehyde. Pretreatment of hepatocytes with either fructose at a concentration of 10 mM or N-acet yl-L-cysteine (NAC) at a concentration of 5.0 mM ameliorated DETX (1 mM)-induced cytotoxicity. Further, the exposure of hepatocytes to DETX resulted in the induction of reactive oxygen species (ROS) and loss of mitochondrial membrane potential, both of which were partially prevented by the addition of NAC. These results indicate that: (1) DETX-induced cytotoxicity is linked to mitochondrial failure and depletion of cellular GSH; (2) insufficient cellular ATP levels derived from mitochondrial dysfunction were, at least in part, ameliorated by the addition of fructose; and (3) GSH loss and/or ROS formation was prevented by NAC. Taken collectively, these results suggest that the onset of toxic effects caused by DETX may be partially attributable to cellular energy stress as well as oxidative stress.The exposure of rat hepatocytes to thioxanthone photoinitiators, especially 2,4diethylthioxanthone (DETX), caused cell death accompanied by the depletion of intracellular ATP and glutathione, and the induction of glutathione disulfide, all of which were partially prevented by the preincubation with N-acetyl-L-cysteine (NAC) or fructose. DETXinduced cytotoxicity was also associated by mitochondrial dysfunction and reactive oxygen species formation, which could be prevented by NAC. These results suggest that DETXinduced cytotoxicity may be attributable to cellular energy stress and/or oxidative stress.

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“…The N-methyl analog 5-MAPB was also reported to show DAT binding and inhibition of reuptake at DAT and SERT (Kim et al 2019). The evaluation of cytotoxic effects of 5-APB and 5-MAPB in hepatocytes has also been reported (Nakagawa et al 2018;Nakagawa et al 2017).…”

Section: Introductionmentioning

confidence: 99%

The psychoactive aminoalkylbenzofuran derivatives, 5-APB and 6-APB, mimic the effects of 3,4-methylenedioxyamphetamine (MDA) on monoamine transmission in male rats

et al. 2020

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RationaleThe non-medical use of new psychoactive substances (NPS) is a worldwide public health concern. The so-called "benzofury" compounds, 5-(2aminopropyl)benzofuran (5-APB) and 6-(2-aminopropyl)benzofuran (6-APB), are NPS with stimulant-like properties in human users. These substances are known to interact with monoamine transporters and 5-HT receptors in transfected cells, but less is known about their effects in animal models. Methods Here, we used in vitro monoamine transporter assays in rat brain synaptosomes to characterize the effects of 5-APB and 6-APB, together with their Nmethyl derivatives 5-MAPB and 6-MAPB, in comparison to 3,4methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA). In vivo neurochemical and behavioral effects of 5-APB (0.3 and 1.0 mg/kg, i.v.) and 6-APB (0.3 and 1.0 mg/kg, i.v.) were assessed in comparison to MDA (1.0 and 3.0 mg/kg, i.v.) using microdialysis sampling in the nucleus accumbens of conscious male rats. Results All four benzofuran derivatives were substrate-type releasers at dopamine transporters (DAT), norepinephrine transporters (NET) and serotonin transporters (SERT) with nanomolar potencies, similar to the profile of effects produced by MDA and MDMA. However, the benzofurans were at least 3-fold more potent than MDA and MDMA at evoking transporter-mediated release. Like MDA, both benzofurans induced dose-related elevations in extracellular dopamine and serotonin in the brain, but benzofurans were more potent than MDA. The benzofuran derivatives also induced profound behavioral activation characterized by forward locomotion which lasted for at least 2 h post-injection. Conclusions Overall, benzofurans are more potent than MDA in vitro and in vivo, producing sustained stimulant-like effects in rats. These data suggest that benzofuran-type compounds may have abuse liability, and could pose risks for adverse effects, especially if used in conjunction with abused drugs or medications which enhance monoamine transmission in the brain.

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Preventive effects of fructose and N‐acetyl‐L‐cysteine against cytotoxicity induced by the psychoactive compounds N‐methyl‐5‐(2‐aminopropyl)benzofuran and 3,4‐methylenedioxy‐N‐methamphetamine in isolated rat hepatocytes

Cited by 6 publications

References 39 publications

<p>Short Communication: Fructose-Enhanced Antibacterial Activity of Self-Assembled Nano-Peptide Amphiphiles for Treating Antibiotic-Resistant Bacteria</p>

<p>Short Communication: Fructose-Enhanced Antibacterial Activity of Self-Assembled Nano-Peptide Amphiphiles for Treating Antibiotic-Resistant Bacteria</p>

Cytotoxic effects of thioxanthone derivatives as photoinitiators on isolated rat hepatocytes

The psychoactive aminoalkylbenzofuran derivatives, 5-APB and 6-APB, mimic the effects of 3,4-methylenedioxyamphetamine (MDA) on monoamine transmission in male rats

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