PMID- 28949027
OWN - NLM
STAT- MEDLINE
DCOM- 20180723
LR  - 20181221
IS  - 1099-1263 (Electronic)
IS  - 0260-437X (Linking)
VI  - 38
IP  - 2
DP  - 2018 Feb
TI  - 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.
PG  - 284-291
LID - 10.1002/jat.3523 [doi]
AB  - 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.
CI  - Copyright (c) 2017 John Wiley & Sons, Ltd.
FAU - Nakagawa, Yoshio
AU  - Nakagawa Y
AUID- ORCID: 0000-0003-3156-467X
AD  - Division of Toxicology, Tokyo Metropolitan Institute of Public Health, 3-24-1, 
      Hyakunin-cho, Shinjuku-ku, Tokyo, 169-0073, Japan.
FAU - Suzuki, Toshinari
AU  - Suzuki T
AD  - Division of Toxicology, Tokyo Metropolitan Institute of Public Health, 3-24-1, 
      Hyakunin-cho, Shinjuku-ku, Tokyo, 169-0073, Japan.
FAU - Inomata, Akiko
AU  - Inomata A
AD  - Division of Toxicology, Tokyo Metropolitan Institute of Public Health, 3-24-1, 
      Hyakunin-cho, Shinjuku-ku, Tokyo, 169-0073, Japan.
LA  - eng
PT  - Journal Article
DEP - 20170926
PL  - England
TA  - J Appl Toxicol
JT  - Journal of applied toxicology : JAT
JID - 8109495
RN  - 0 (Benzofurans)
RN  - 0 (Propylamines)
RN  - 0 (Psychotropic Drugs)
RN  - 2M3825704H (5-(2-aminopropyl)benzofuran)
RN  - 30237-26-4 (Fructose)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/*pharmacology
MH  - Animals
MH  - Benzofurans/*toxicity
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Energy Metabolism/drug effects
MH  - Fructose/*pharmacology
MH  - Hepatocytes/*drug effects/metabolism/pathology
MH  - Male
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*toxicity
MH  - Oxidative Stress/drug effects
MH  - Propylamines/*toxicity
MH  - Psychotropic Drugs/*toxicity
MH  - Rats, Inbred F344
OTO - NOTNLM
OT  - 5-MAPB
OT  - MDMA
OT  - N-acetyl-L-cysteine
OT  - cytotoxicity
OT  - designer drugs
OT  - fructose
OT  - mitochondrial dysfunction
OT  - oxidative stress
OT  - rat hepatocytes
EDAT- 2017/09/28 06:00
MHDA- 2018/07/24 06:00
CRDT- 2017/09/27 06:00
PHST- 2017/07/24 00:00 [received]
PHST- 2017/08/15 00:00 [accepted]
PHST- 2017/09/28 06:00 [pubmed]
PHST- 2018/07/24 06:00 [medline]
PHST- 2017/09/27 06:00 [entrez]
AID - 10.1002/jat.3523 [doi]
PST - ppublish
SO  - J Appl Toxicol. 2018 Feb;38(2):284-291. doi: 10.1002/jat.3523. Epub 2017 Sep 26.