Publication: Resveratrol attenuates hepatic inflammation and oxidative stress in collagen-induced arthritis (CIA) mice via the Nrf2/Keap1 pathway
Authors
Suhuan Chen ; Haomiao Liu ; Mengyan Zhang ; Mengmeng Chen ; Wuqi Chen ; Guangyi Chen ; Weilu Gao ; Tao Yao ; Xiaoyu Chen ; Xuefei Fan1
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Publisher
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DOI
https://doi.org/10.14670/HH-18-962
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info:eu-repo/semantics/article
Description
Abstract
Background. Rheumatoid arthritis can affect
extra-articular organs such as the liver, and the problem
of drug-induced liver injury caused by traditional
antirheumatic drugs for improving the condition cannot
be ignored. This study aims to investigate the therapeutic
effects of resveratrol (Res) on hepatic inflammation and
oxidative stress in mice with collagen-induced arthritis
(CIA) and to elucidate the relationship between the
regulatory mechanisms of the nuclear factor erythroid 2
related factor 2 (Nrf2)/Kelch-like ECH-associated
protein 1 (Keap1) signaling pathway.
Methods. In this study, we used chicken type II
collagen in combination with complete Freund's
adjuvant to induce arthritis in a mouse model, and Res
was administered by tube feeding to detect the serum
biochemical liver function and inflammation levels,
oxidative stress, and apoptosis in the livers of mice. An
in vitro cellular model of liver inflammation and
oxidative stress was established by treating mouse
primary hepatocytes (MPHs) with tumor necrosis factor
α (TNF-α) and H2O2. The intrinsic mechanism of Res in
attenuating hepatic inflammation and oxidative stress in
CIA mice was explored by treating MPHs with an Nrf2
inhibitor and Keap1 overexpression plasmid.
Results. Res significantly reduced the levels of
inflammation and oxidative stress in liver tissues of CIA
mice as well as in MPHs treated with TNF-α and H2O2
and activated the Nrf2/Keap1 signaling pathway.
Inflammation and oxidative stress levels in MPHs were exacerbated by the use of Nrf2 inhibitors and Keap1
overexpression, which promoted apoptosis.
Conclusion. This study demonstrated the intrinsic
mechanism of Res of attenuating hepatic inflammation
and oxidative stress in CIA mice through the Nrf2/Keap1
pathway, which provides a new idea for finding
hepatoprotective treatments for rheumatoid arthritis.
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