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

Journal of Applied Toxicology - Tập 38 Số 2 - Trang 284-291 - 2018
Yoshio Nakagawa1, Toshinari Suzuki1, Akiko Inomata1
1Division of Toxicology, Tokyo Metropolitan Institute of Public Health, 3-24-1, Hyakunin-cho, Shinjuku-ku, Tokyo, 169-0073 Japan

Tóm tắt

AbstractPsychoactive 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.

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Journal of Applied Toxicology

Tập 38 Số 2

284-291

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