PMID- 27291301
OWN - NLM
STAT- MEDLINE
DCOM- 20171215
LR  - 20181221
IS  - 1099-1263 (Electronic)
IS  - 0260-437X (Linking)
VI  - 37
IP  - 3
DP  - 2017 Mar
TI  - Cytotoxic effects of psychotropic benzofuran derivatives, 
      N-methyl-5-(2-aminopropyl)benzofuran and its N-demethylated derivative, on 
      isolated rat hepatocytes.
PG  - 243-252
LID - 10.1002/jat.3351 [doi]
AB  - The novel psychoactive compounds derived from amphetamine have been illegally 
      abused as recreational drugs, some of which are known to be hepatotoxic in humans 
      and experimental animals. The cytotoxic effects and mechanisms of 
      5-(2-aminopropyl)benzofuran (5-APB) and N-methyl-5-(2-aminopropyl)benzofuran 
      (5-MAPB), both of which are benzofuran analogues of amphetamine, and 
      3,4-methylenedioxy-N-methamphetamine (MDMA) were studied in freshly isolated rat 
      hepatocytes. 5-MAPB caused not only concentration-dependent (0-4.0 mm) and 
      time-dependent (0-3 h) cell death accompanied by the depletion of cellular ATP 
      and reduced glutathione and protein thiol levels, but also accumulation of 
      oxidized glutathione. Of the other analogues examined at a concentration of 4 mm, 
      5-MAPB/5-APB-induced cytotoxicity with the production of reactive oxygen species 
      and loss of mitochondrial membrane potential was greater than that induced by 
      MDMA. In isolated rat liver mitochondria, the benzofurans resulted in a greater 
      increase in the rate of state 4 oxygen consumption than did MDMA, with a decrease 
      in the rate of state 3 oxygen consumption. Furthermore, the benzofurans caused 
      more of a rapid mitochondrial swelling dependent on the mitochondrial 
      permeability transition than MDMA. 5-MAPB at a weakly toxic level (1 mm) was 
      metabolized slowly: levels of 5-MAPB and 5-APB were approximately 0.9 mm and 
      50 mum, respectively, after 3 h incubation. Taken collectively, these results 
      indicate that mitochondria are target organelles for the benzofuran analogues and 
      MDMA, which elicit cytotoxicity through mitochondrial failure, and the onset of 
      cytotoxicity may depend on the initial and/or residual concentrations of 5-MAPB 
      rather than on those of its metabolite 5-APB. Copyright (c) 2016 John Wiley & Sons, 
      Ltd.
CI  - Copyright (c) 2016 John Wiley & Sons, Ltd.
FAU - Nakagawa, Yoshio
AU  - Nakagawa Y
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 Environmental Health, Tokyo Metropolitan Institute of Public Health, 
      3-24-1, Hyakunin-cho, Shinjuku-ku, Tokyo, 169-0073, Japan.
FAU - Tada, Yukie
AU  - Tada Y
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 - 20160613
PL  - England
TA  - J Appl Toxicol
JT  - Journal of applied toxicology : JAT
JID - 8109495
RN  - 0 (Benzofurans)
RN  - 0 (Designer Drugs)
RN  - 0 (N-methyl-5-(2 aminopropyl)benzofuran)
RN  - 0 (Propylamines)
RN  - 0 (Reactive Oxygen Species)
RN  - 2M3825704H (5-(2-aminopropyl)benzofuran)
RN  - 44RAL3456C (Methamphetamine)
SB  - IM
MH  - Animals
MH  - Benzofurans/metabolism/*toxicity
MH  - Biotransformation
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Designer Drugs/metabolism/*toxicity
MH  - Dose-Response Relationship, Drug
MH  - Hepatocytes/*drug effects/metabolism/pathology
MH  - Male
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - Methamphetamine/*analogs & derivatives/metabolism/toxicity
MH  - Mitochondria, Liver/drug effects
MH  - Mitochondrial Membranes/drug effects
MH  - Permeability
MH  - Propylamines/metabolism/*toxicity
MH  - Rats, Inbred F344
MH  - Reactive Oxygen Species/metabolism
OTO - NOTNLM
OT  - 5-APB
OT  - 5-MAPB
OT  - benzofurans
OT  - cytotoxicity
OT  - designer drugs
OT  - metabolism
OT  - mitochondrial dysfunction
OT  - oxidative stress
OT  - rat hepatocytes
EDAT- 2016/06/14 06:00
MHDA- 2017/12/16 06:00
CRDT- 2016/06/14 06:00
PHST- 2016/03/23 00:00 [received]
PHST- 2016/04/13 00:00 [revised]
PHST- 2016/04/24 00:00 [accepted]
PHST- 2016/06/14 06:00 [pubmed]
PHST- 2017/12/16 06:00 [medline]
PHST- 2016/06/14 06:00 [entrez]
AID - 10.1002/jat.3351 [doi]
PST - ppublish
SO  - J Appl Toxicol. 2017 Mar;37(3):243-252. doi: 10.1002/jat.3351. Epub 2016 Jun 13.