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Acamprosate Protects Against Adjuvant-Induced Arthritis in Rats via Blocking the ERK/MAPK and NF-κB Signaling Pathway

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Abstract

Osteoarthritis is a type of joint disease that results from the breakdown of joint cartilage and underlying bone and is believed to be caused by mechanical stress on the joint and low-grade inflammatory processes. Acamprosate significantly ameliorates the pathological features of experimental autoimmune encephalomyelitis due to its anti-inflammatory effect. The aims of the present study were to investigate the anti-arthritis activities of acamprosate and elucidate the underlying mechanisms. Adjuvant-induced arthritis (AIA) was induced by intradermal injection of complete Freund’s adjuvant. Male Wistar rats were randomly divided into five groups: (1) sham control group, (2) AIA group, (3) acamprosate 10 mg/kg (AIA + ACA10), (4) acamprosate 30 mg/kg (AIA + ACA30), and (5) acamprosate 100 mg/kg (AIA + ACA100). Paw swelling and the arthritis index were measured, and the production of IL-1β, IL-6, and TNF-α was detected by ELISA in serum. The expression of inflammation-related molecules, including c-Raf, ERK1/2, and NF-κB, was determined by Western blotting. We found that acamprosate significantly suppressed paw swelling and the arthritis index in AIA rats. Moreover, acamprosate also significantly suppressed the production of TNF-α, IL-1β, and IL-6 in serum, which is elevated by AIA induction. Finally, acamprosate inhibited p-c-Raf and p-ERK1/2 and NF-κB activation after AIA treatment. These results indicate that acamprosate has an anti-inflammatory effect on adjuvant-induced arthritic rats via inhibiting the ERK/MAPK and NF-κB signaling pathways, and acamprosate may serve as a promising novel therapeutic agent for osteoarthritis.

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Acknowledgements

This study was supported by National Natural Science Foundation of China (No. 81772311).

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Authors

Contributions

Conceived and designed the experiments: XS. Performed the experiments: PJ JR. Analyzed the data: SM WR. Wrote the paper: XS PJ.

Corresponding author

Correspondence to Sanzhong Xu.

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The experiment was approved by the ethical guidelines of the Zhejiang University Animal Experimentation Committee.

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The authors declare that they have no competing interests.

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Pan, J., Jin, R., Shen, M. et al. Acamprosate Protects Against Adjuvant-Induced Arthritis in Rats via Blocking the ERK/MAPK and NF-κB Signaling Pathway. Inflammation 41, 1194–1199 (2018). https://doi.org/10.1007/s10753-018-0766-y

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  • DOI: https://doi.org/10.1007/s10753-018-0766-y

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