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.
Yoshio Nakagawa, Toshinari Suzuki, Akiko Inomata
Journal of Applied Toxicology February 2018 DOI: 10.1002/jat.3523 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro study Peer reviewed |
|---|---|
| Population | Rat hepatocytes |
| Interventions | 5-MAPB MDMA fructose N-acetyl-L-cysteine (NAC) |
| Dose | 5-MAPB and MDMA: 0-4 mM; fructose: 10 mM; NAC: 2.5 mM |
| Duration | 0-3 hours |
| Topics | MDMA |
| Keywords | 5-mapb N-acetyl-l-cysteine Cytotoxicity Designer drugs Fructose Mitochondrial dysfunction Oxidative stress Rat hepatocytes |
| Key points | 5-MAPB and MDMA caused concentration- and time-dependent death of rat hepatocytes, with 5-MAPB more toxic than MDMA. Toxicity was accompanied by ATP and reduced glutathione depletion, increased oxidized glutathione, and loss of mitochondrial membrane potential. Fructose (10 mM) or N-acetyl-L-cysteine (2.5 mM) pretreatment prevented cytotoxicity, suggesting toxicity involves mitochondrial failure and oxidative stress. |
Abstract
Psychoactive compounds, N-methyl-5-(2-aminopropyl)benzofuran (5-MAPB) and 3,4-methylenedioxy-N-methamphetamine (MDMA), are known to be hepatotoxic in humans and/or experimental animals. As previous studies suggested that these compounds elicited cytotoxicity via mitochondrial dysfunction and/or oxidative stress in rat hepatocytes, the protective effects of fructose and N-acetyl-l-cysteine (NAC) on 5-MAPB- and MDMA-induced toxicity were studied in rat hepatocytes. These drugs caused not only concentration-dependent (0-4 mm) and time-dependent (0-3 hours) cell death accompanied by the depletion of cellular levels of adenosine triphosphate (ATP) and glutathione (reduced form; GSH) but also an increase in the oxidized form of GSH. The toxic effects of 5-MAPB were greater than those of MDMA. Pretreatment of hepatocytes with either fructose at a concentration of 10 mm or NAC at a concentration of 2.5 mm prevented 5-MAPB-/MDMA-induced cytotoxicity. In addition, the exposure of hepatocytes to 5-MAPB/MDMA caused the loss of mitochondrial membrane potential, although the preventive effect of fructose was weaker than that of NAC. These results suggest that: (1) 5-MAPB-/MDMA-induced cytotoxicity is linked to mitochondrial failure and depletion of cellular GSH; (2) insufficient cellular ATP levels derived from mitochondrial dysfunction were ameliorated, at least in part, by the addition of fructose; and (3) GSH loss via oxidative stress was prevented by NAC. Taken collectively, these results indicate that the onset of toxic effects caused by 5-MAPB/MDMA may be partially attributable to cellular energy stress as well as oxidative stress.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 2
- Locomotor and discriminative stimulus effects of three benzofuran compounds in comparison to abused psychostimulants Drug and Alcohol Dependence Reports August 10, 2023
- The psychoactive aminoalkylbenzofuran derivatives, 5-APB and 6-APB, mimic the effects of 3,4-methylenedioxyamphetamine (MDA) on monoamine transmission in male rats. Psychopharmacology December 2020
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