PMID- 31336028
OWN - NLM
STAT- MEDLINE
DCOM- 20200110
LR  - 20200110
IS  - 1872-8081 (Electronic)
IS  - 0951-6433 (Linking)
VI  - 45
IP  - 4
DP  - 2019 Jul
TI  - Combination of metformin and luteolin synergistically protects carbon 
      tetrachloride-induced hepatotoxicity: Mechanism involves antioxidant, 
      anti-inflammatory, antiapoptotic, and Nrf2/HO-1 signaling pathway.
PG  - 598-606
LID - 10.1002/biof.1521 [doi]
AB  - Liver diseases are one of the fatal disorders due to the vital role of the liver. 
      Carbon tetrachloride (CCl(4) ) is the most perceived chemical substance utilized 
      in developing models of hepatic damage. Metformin (Met) is a potent antidiabetic 
      and redox modulatory agent that has shown anticancer and protective effects on 
      various organs. Therefore, addition of therapy with natural antioxidative agents 
      or herbal extracts shows defensive impacts against different injuries inside the 
      body. Luteolin (Lut) can be found in several customary Chinese remedies. It has 
      been reported for various pharmacological actions such as antitumor, 
      antioxidative, and anti-inflammatory impacts. Here, the liver injury rat model 
      was established using CCl(4) (1.00 mL/kg body weight) in vivo. The protective 
      roles of Met and Lut separately or in combination were observed in hepatotoxicity 
      induced by CCl(4) . The result was shown that both Met and Lut, while 
      individually used, were normally active in diminishing CCl(4) -caused 
      hepatotoxicity. The combination of two drugs performed synergistically to improve 
      liver damage caused by CCl(4) , as shown by the considerably improved liver 
      dysfunction. Met and Lut showed highly antioxidative effects on CCl(4) -treated 
      rats moderately by increasing the activities and expression of the antioxidant 
      enzymes. Along with this, a combination of Met and Lut significantly suppressed 
      inflammatory responses, which is evidenced by the reduced level of inflammatory 
      cytokines together with interleukin 1 beta (IL-1beta), tumor necrosis factor alpha 
      (TNF-alpha), and interleukin 6 (IL-6). Additionally, CCl(4) -agitated apoptosis was 
      intensely reduced by Met and Lut through reducing cleaved caspase-3 and Bax 
      (pro-apoptotic factor) while increasing Bcl-2 (antiapoptotic factor) signaling 
      pathways. Cotreatments of Met and Lut upregulated nuclear factor erythroid 
      2-related factor 2 (NRF2) and heme oxygenase-1 (HO-1) expression in the CCl(4) 
      -intoxicated rat's liver. The above result recommended that combination of Met 
      and Lut may have a substantial potential and synergizing impact against CCl(4) 
      -induced hepatotoxicity.
CI  - (c) 2019 International Union of Biochemistry and Molecular Biology.
FAU - Yan, Yang
AU  - Yan Y
AUID- ORCID: 0000-0002-7270-5849
AD  - Department of Digestive Medicine, Hefei Second People's Hospital, Hefei, China.
FAU - Jun, Chen
AU  - Jun C
AD  - Department of Digestive Medicine, Hefei Second People's Hospital, Hefei, China.
FAU - Lu, Yang
AU  - Lu Y
AD  - Department of Digestive Medicine, Hefei Second People's Hospital, Hefei, China.
FAU - Jiangmei, Song
AU  - Jiangmei S
AD  - Department of Internal Medicine, CAS Cancer Hospital, Hefei, China.
LA  - eng
PT  - Journal Article
DEP - 20190723
PL  - Netherlands
TA  - Biofactors
JT  - BioFactors (Oxford, England)
JID - 8807441
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Antioxidants)
RN  - 0 (Bax protein, rat)
RN  - 0 (Bcl2 protein, rat)
RN  - 0 (Drug Combinations)
RN  - 0 (IL1B protein, rat)
RN  - 0 (Il6 protein, rat)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Interleukin-6)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Nfe2l2 protein, rat)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 9100L32L2N (Metformin)
RN  - CL2T97X0V0 (Carbon Tetrachloride)
RN  - EC 1.14.14.18 (Heme Oxygenase (Decyclizing))
RN  - EC 1.14.14.18 (Hmox1 protein, rat)
RN  - EC 3.4.22.- (Casp3 protein, rat)
RN  - EC 3.4.22.- (Caspase 3)
RN  - KUX1ZNC9J2 (Luteolin)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Antioxidants/*pharmacology
MH  - Apoptosis/drug effects
MH  - Carbon Tetrachloride/administration & dosage
MH  - Caspase 3/genetics/metabolism
MH  - Chemical and Drug Induced Liver Injury/*drug 
      therapy/genetics/metabolism/pathology
MH  - Drug Combinations
MH  - Drug Synergism
MH  - Gene Expression Regulation
MH  - Heme Oxygenase (Decyclizing)/*genetics/metabolism
MH  - Interleukin-1beta/antagonists & inhibitors/genetics/metabolism
MH  - Interleukin-6/antagonists & inhibitors/genetics/metabolism
MH  - Liver/drug effects/metabolism/pathology
MH  - Liver Function Tests
MH  - Luteolin/*pharmacology
MH  - Male
MH  - Metformin/*pharmacology
MH  - NF-E2-Related Factor 2/*genetics/metabolism
MH  - Proto-Oncogene Proteins c-bcl-2/genetics/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Signal Transduction/drug effects
MH  - Tumor Necrosis Factor-alpha/antagonists & inhibitors/genetics/metabolism
MH  - bcl-2-Associated X Protein/genetics/metabolism
OTO - NOTNLM
OT  - CCl4
OT  - HO-1
OT  - Nrf2
OT  - apoptosis
OT  - inflammatory cytokines
OT  - luteolin
OT  - metformin
EDAT- 2019/07/25 06:00
MHDA- 2020/01/11 06:00
CRDT- 2019/07/24 06:00
PHST- 2019/04/18 00:00 [received]
PHST- 2019/05/06 00:00 [accepted]
PHST- 2019/07/25 06:00 [pubmed]
PHST- 2020/01/11 06:00 [medline]
PHST- 2019/07/24 06:00 [entrez]
AID - 10.1002/biof.1521 [doi]
PST - ppublish
SO  - Biofactors. 2019 Jul;45(4):598-606. doi: 10.1002/biof.1521. Epub 2019 Jul 23.