PMID- 30535447
OWN - NLM
STAT- MEDLINE
DCOM- 20190528
LR  - 20211018
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Print)
IS  - 1791-2997 (Linking)
VI  - 19
IP  - 2
DP  - 2019 Feb
TI  - alpha‑lipoic acid protects against carbon tetrachloride‑induced liver cirrhosis 
      through the suppression of the TGF‑beta/Smad3 pathway and autophagy.
PG  - 841-850
LID - 10.3892/mmr.2018.9719 [doi]
AB  - alpha‑lipoic acid (ALA) is a naturally occurring antioxidant with protective effects 
      against various hepatic injuries. The aim of the present study was to investigate 
      the mechanisms by which ALA protects the liver from carbon tetrachloride 
      (CCl4)‑induced liver cirrhosis. The widely used liver cirrhosis rat model was 
      established via an intraperitoneal injection of 2 mg/kg 50% CCl4, three 
      times/week for 8 weeks. Simultaneously, 50 or 100 mg/kg ALA was orally 
      administrated to the rats every day for 8 weeks. The activity of alanine 
      aminotransferase (ALT) and aspartate aminotransferase (AST) was detected in the 
      serum. The pathological liver injuries were analyzed using hematoxylin and eosin 
      and Masson's trichrome staining. The principal factors involved in the 
      transforming growth factor‑beta (TGF‑beta)/mothers against decapentaplegic homolog 9 
      (Smad3) and protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathways 
      and in autophagy were examined using reverse transcription‑quantitative 
      polymerase chain reaction or western blot analysis. The results demonstrated that 
      the administration of ALA alleviated CCl4‑induced liver injury, as demonstrated 
      by decreased ALT and AST activity, improved pathological injuries and reduced 
      collagen deposition. The CCl4‑induced increase in TGF‑beta and phosphorylated‑Smad3 
      expression levels was additionally inhibited by treatment with ALA. Furthermore, 
      the administration of ALA reversed the CCl4‑induced upregulation of light chain 
      3II and Beclin‑1, and downregulation of p62. The CCl4‑induced suppression of the 
      AKT/mTOR pathway was additionally restored following treatment with ALA. In 
      combination, the results of the present study demonstrated that ALA was able to 
      protect CCl4‑induced liver cirrhosis, an effect that may be associated with 
      inactivation of the TGF‑beta/Smad3 pathway and suppression of autophagy.
FAU - Liu, Guangwei
AU  - Liu G
AD  - Spleen, Stomach and Hepatobiliary Department, The First Affiliated Hospital, 
      Henan University of Chinese Medicine, Zhengzhou, Henan 450004, P.R. China.
FAU - Liu, Jiangkai
AU  - Liu J
AD  - Spleen, Stomach and Hepatobiliary Department, The First Affiliated Hospital, 
      Henan University of Chinese Medicine, Zhengzhou, Henan 450004, P.R. China.
FAU - Pian, Linping
AU  - Pian L
AD  - Spleen, Stomach and Hepatobiliary Department, The First Affiliated Hospital, 
      Henan University of Chinese Medicine, Zhengzhou, Henan 450004, P.R. China.
FAU - Gui, Songlin
AU  - Gui S
AD  - Department of Emergency Medicine, Zhengzhou Chinese Medicine Hospital, Zhengzhou, 
      Henan 450007, P.R. China.
FAU - Lu, Baoping
AU  - Lu B
AD  - Spleen, Stomach and Hepatobiliary Department, The First Affiliated Hospital, 
      Henan University of Chinese Medicine, Zhengzhou, Henan 450004, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20181204
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Protective Agents)
RN  - 0 (Smad3 Protein)
RN  - 0 (Smad3 protein, rat)
RN  - 0 (Transforming Growth Factor beta)
RN  - 73Y7P0K73Y (Thioctic Acid)
RN  - CL2T97X0V0 (Carbon Tetrachloride)
RN  - EC 2.6.1.1 (Aspartate Aminotransferases)
RN  - EC 2.6.1.2 (Alanine Transaminase)
SB  - IM
MH  - Alanine Transaminase/blood
MH  - Animals
MH  - Aspartate Aminotransferases/blood
MH  - Autophagy/*drug effects
MH  - Carbon Tetrachloride/pharmacology
MH  - Down-Regulation/drug effects
MH  - Liver/drug effects/metabolism
MH  - Liver Cirrhosis/blood/chemically induced/*drug therapy/metabolism
MH  - Male
MH  - Protective Agents/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/*drug effects
MH  - Smad3 Protein/*metabolism
MH  - Thioctic Acid/*pharmacology
MH  - Transforming Growth Factor beta/*metabolism
MH  - Up-Regulation/drug effects
PMC - PMC6323260
OTO - NOTNLM
OT  - liver cirrhosis
OT  - alpha-lipoic acid transforming growth factor-beta/Smad3
OT  - autophagy
OT  - protein kinase B/mammalian target of rapamycin
EDAT- 2018/12/12 06:00
MHDA- 2019/05/29 06:00
PMCR- 2018/12/04
CRDT- 2018/12/12 06:00
PHST- 2018/04/25 00:00 [received]
PHST- 2018/09/28 00:00 [accepted]
PHST- 2018/12/12 06:00 [pubmed]
PHST- 2019/05/29 06:00 [medline]
PHST- 2018/12/12 06:00 [entrez]
PHST- 2018/12/04 00:00 [pmc-release]
AID - mmr-19-02-0841 [pii]
AID - 10.3892/mmr.2018.9719 [doi]
PST - ppublish
SO  - Mol Med Rep. 2019 Feb;19(2):841-850. doi: 10.3892/mmr.2018.9719. Epub 2018 Dec 4.