PMID- 32471964
OWN - NLM
STAT- MEDLINE
DCOM- 20210823
LR  - 20210823
IS  - 0300-5283 (Print)
IS  - 0300-5283 (Linking)
VI  - 75
IP  - Suppl 1
DP  - 2020 May
TI  - Uric acid induces liver fibrosis through activation of inflammatory mediators and 
      proliferating hepatic stellate cell in mice.
PG  - 14-18
AB  - INTRODUCTION: Uric acid is associated with cardiometabolic risk factor and 
      severity of liver damage. The mechanism of uric acid inducing liver damage is 
      still elusive. This study elucidates the development of liver fibrosis under 
      hyperuricemia. METHODS AND MATERIALS: Hyperuricemia model was performed in male 
      Swiss Webster mice. Intraperitoneally injection of uric acid (125mg/kg body 
      weight) was done for 7 and 14 days (UA7 and UA14 groups). Meanwhile, the UAL 
      groups were injected with uric acid and followed by the administration of 
      allopurinol (UAL7 and UAL14 groups). On the due date, mice were sacrificed, and 
      liver was harvested. Uric acid, SGOT, SGPT, and albumin level were measured from 
      the serum. The mRNA expression of TLR4, MCP1, CD68, and collagen1 were assessed 
      through RT-PCR. Liver fibrosis was quantified through Sirius red staining, while 
      the number of hepatic stellates cells (HSCs) and TLR4 were assessed through IHC 
      staining. RESULTS: Uric acid induction for 7 and 14 days stimulated an increase 
      of both SGOT and SGPT serum levels. Followed by enhanced inflammatory mediators: 
      Toll-like receptor-4 (TLR- 4), Monocyte Chemoattractant Protein-1 (MCP-1) and 
      Cluster of Differentiation 68 (CD68) mRNA expression in the liver (p<0.05). The 
      histological findings showed that the UA7 and UA14 groups had higher liver 
      fibrosis scores (p<0.05), collagen I mRNA expression (p<0.05), and the number of 
      HSCs (p<0.05) compared to Control group. Administration of allopurinol showed 
      amelioration of uric acid and liver enzymes levels which followed by inflammatory 
      mediators, liver fibrosis and collagen1, and hepatic stellate cells 
      significantly. CONCLUSION: Therefore, uric acid augmented the liver fibrosis by 
      increasing the number of hepatic stellate cells.
FAU - Sari, D C R
AU  - Sari DCR
AD  - Universitas Gadjah Mada, Public Health, and Nursing, Faculty of Medicine, 
      Department of Anatomy, Jl. Farmako Sekip Utara, Yogyakarta, Indonesia. 
      KMJohnChan@yahoo.com.
FAU - Soetoko, A S
AU  - Soetoko AS
AD  - Universitas Gadjah Mada, Public Health, and Nursing, Faculty of Medicine, 
      Department of Anatomy, Jl. Farmako Sekip Utara, Yogyakarta, Indonesia.
FAU - Soetoko, A S
AU  - Soetoko AS
AD  - Universitas Islam Sultan Agung, Faculty of Medicine, Department of Anatomy, 
      Semarang, Indonesia.
FAU - Romi, M M
AU  - Romi MM
AD  - Universitas Gadjah Mada, Public Health, and Nursing, Faculty of Medicine, 
      Department of Anatomy, Jl. Farmako Sekip Utara, Yogyakarta, Indonesia.
FAU - Tranggono, U
AU  - Tranggono U
AD  - Universitas Gadjah Mada, Public Health, and Nursing, Faculty of Medicine, 
      Department of Surgery, Jl. Farmako Sekip Utara, Yogyakarta, Indonesia.
FAU - Setyaningsih, W A W
AU  - Setyaningsih WAW
AD  - Universitas Gadjah Mada, Public Health, and Nursing, Faculty of Medicine, 
      Department of Anatomy, Jl. Farmako Sekip Utara, Yogyakarta, Indonesia.
FAU - Arfian, N
AU  - Arfian N
AD  - Universitas Gadjah Mada, Public Health, and Nursing, Faculty of Medicine, 
      Department of Anatomy, Jl. Farmako Sekip Utara, Yogyakarta, Indonesia. 
      nur_arfian@ugm.ac.id.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Malaysia
TA  - Med J Malaysia
JT  - The Medical journal of Malaysia
JID - 0361547
RN  - 268B43MJ25 (Uric Acid)
SB  - IM
MH  - Animals
MH  - Hepatic Stellate Cells/*drug effects
MH  - Liver Cirrhosis/*chemically induced/*immunology
MH  - Mice
MH  - Uric Acid/*metabolism
EDAT- 2020/05/31 06:00
MHDA- 2021/08/24 06:00
CRDT- 2020/05/31 06:00
PHST- 2020/05/31 06:00 [entrez]
PHST- 2020/05/31 06:00 [pubmed]
PHST- 2021/08/24 06:00 [medline]
PST - ppublish
SO  - Med J Malaysia. 2020 May;75(Suppl 1):14-18.