PMID- 31708533
OWN - NLM
STAT- MEDLINE
DCOM- 20200330
LR  - 20200330
IS  - 1880-3989 (Electronic)
IS  - 0388-1350 (Linking)
VI  - 44
IP  - 11
DP  - 2019
TI  - Estimation of potential risk of allyl alcohol induced liver injury in diabetic 
      patients using type 2 diabetes spontaneously diabetic Torii-Lepr(fa) (SDT fatty) 
      rats.
PG  - 759-776
LID - 10.2131/jts.44.759 [doi]
AB  - In order to estimate the potential risk of chemicals including drug in patients 
      with type 2 diabetes mellitus (T2DM), we investigated allyl alcohol induced liver 
      injury using SD rats and Spontaneously Diabetic Torii-Lepr(fa) (SDT fatty) rats 
      as a model for human T2DM. The diabetic state is one of the risk factors for 
      chemically induced liver injury because of lower levels of glutathione for 
      detoxification by conjugation with chemicals and environmental pollutants and 
      their reactive metabolites. Allyl alcohol is metabolized to a highly reactive 
      unsaturated aldehyde, acrolein, which is detoxified by conjugation with 
      glutathione. Therefore, we used allyl alcohol as a model compound. Our 
      investigations showed that SDT fatty rats appropriately mimic the diabetic state 
      in humans. The profiles of glucose metabolism, hepatic function tests and 
      glutathione synthesis in the SDT fatty rats were similar to those in patients 
      with T2DM. Five-week oral dosing with allyl alcohol to the SDT fatty rats 
      revealed that the allyl alcohol induced liver injury was markedly enhanced in the 
      SDT fatty rats when compared with the SD rats and the difference was considered 
      to be due to lower hepatic detoxification of acrolein, the reactive metabolite of 
      allyl alcohol, by depleted hepatic glutathione synthesis. Taking all the results 
      of the present study into consideration, the potential for allyl alcohol to 
      induce liver injury is considered to be higher in diabetic patients than in 
      healthy humans.
FAU - Takahashi, Tadakazu
AU  - Takahashi T
AD  - Toxicology Research Lab., Central Pharmaceutical Research Institute, JAPAN 
      TOBACCO INC.
AD  - Graduate School of Integrated Pharmaceutical and Nutritional Sciences, Graduate 
      Program in Environmental Health Sciences, University of Shizuoka.
FAU - Matsuura, Chizuru
AU  - Matsuura C
AD  - Toxicology Research Lab., Central Pharmaceutical Research Institute, JAPAN 
      TOBACCO INC.
FAU - Toyoda, Kaoru
AU  - Toyoda K
AD  - Toxicology Research Lab., Central Pharmaceutical Research Institute, JAPAN 
      TOBACCO INC.
FAU - Suzuki, Yusuke
AU  - Suzuki Y
AD  - Toxicology Research Lab., Central Pharmaceutical Research Institute, JAPAN 
      TOBACCO INC.
FAU - Yamada, Naohito
AU  - Yamada N
AD  - Toxicology Research Lab., Central Pharmaceutical Research Institute, JAPAN 
      TOBACCO INC.
FAU - Kobayashi, Akio
AU  - Kobayashi A
AD  - Toxicology Research Lab., Central Pharmaceutical Research Institute, JAPAN 
      TOBACCO INC.
FAU - Sugai, Shoichiro
AU  - Sugai S
AD  - Toxicology Research Lab., Central Pharmaceutical Research Institute, JAPAN 
      TOBACCO INC.
FAU - Shimoi, Kayoko
AU  - Shimoi K
AD  - Graduate School of Integrated Pharmaceutical and Nutritional Sciences, Graduate 
      Program in Environmental Health Sciences, University of Shizuoka.
LA  - eng
PT  - Journal Article
PL  - Japan
TA  - J Toxicol Sci
JT  - The Journal of toxicological sciences
JID - 7805798
RN  - 0 (Propanols)
RN  - 3W678R12M0 (allyl alcohol)
RN  - GAN16C9B8O (Glutathione)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - *Chemical and Drug Induced Liver Injury, Chronic/pathology
MH  - *Diabetes Mellitus, Type 2
MH  - Disease Models, Animal
MH  - Glucose/metabolism
MH  - Glutathione/metabolism
MH  - Humans
MH  - Liver/drug effects/metabolism/pathology
MH  - Male
MH  - Propanols/*toxicity
MH  - Rats, Sprague-Dawley
MH  - Risk
OTO - NOTNLM
OT  - Allyl alcohol
OT  - Glutathione
OT  - Hepatotoxicity
OT  - SDT fatty rats
OT  - Type2 diabetes
EDAT- 2019/11/12 06:00
MHDA- 2020/03/31 06:00
CRDT- 2019/11/12 06:00
PHST- 2019/11/12 06:00 [entrez]
PHST- 2019/11/12 06:00 [pubmed]
PHST- 2020/03/31 06:00 [medline]
AID - 10.2131/jts.44.759 [doi]
PST - ppublish
SO  - J Toxicol Sci. 2019;44(11):759-776. doi: 10.2131/jts.44.759.