Resolvin D1 Attenuates Inflammation and Pelvic Pain Associated with EAP by Inhibiting Oxidative Stress and NLRP3 Inflammasome Activation via the Nrf2/HO-1 Pathway

Abstract

Background

Resolvin D1 (RvD1), a member of the specialized pro-resolving lipid mediators family, has a potent anti-inflammatory effect and alleviates tissue damage. The purpose of the current research was to study the effect of RvD1 on CP/CPPS and the underlying mechanisms using a mouse model of experimental autoimmune prostatitis (EAP) mice.

Materials and Methods

The EAP mouse model was successfully established, and was used to test the therapeutic effect of RvD1. Hematoxylin-eosin staining and dihydroethidium staining were used to evaluate the histological changes and oxidative stress levels of prostate tissues. Chronic pelvic pain was assessed by applying von Frey filaments to the lower abdomen. The superoxide dismutase enzyme and malondialdehyde levels were detected using enzyme-linked immunosorbent assay (ELISA). The levels of inflammation-related cytokines, including IL-1β, IL-6, and TNF-α were detected by ELISA.

Results

RvD1 treatment ameliorated prostatic inflammation and the pelvic pain of EAP mice. RvD1 treatment could inhibit activation of the NLRP3 inflammasome and oxidative stress. RvD1 treatment could activate Nrf2/HO-1 signaling in mice with EAP. Blockade of Nrf2/HO-1 signaling abolished the RvD1-mediated inhibition of oxidative stress, NLRP3 inflammasome activation and the anti-inflammatory effect of RvD1 in EAP.

Conclusion

RvD1 treatment can reduce inflammatory cell infiltration in prostate tissue and attenuate pelvic pain associated with EAP by inhibiting oxidative stress and NLRP3 inflammasome activation via the Nrf2/HO-1 pathway. These results provide new insights that RvD1 has the potential as an effective agent in the treatment of EAP.

Keywords:

• chronic prostatitis and chronic pelvic pain syndrome
• CP/CPPS
• resolvin D1
• inflammation
• NLRP3 inflammasome
• oxidative stress

Data Sharing Statement

The data used to support the findings of this study are available from the corresponding author upon request.

Ethics Approval and Informed Consent

All animal procedures were approved by the Committee for Animal Care and Use of the Animal Center of Anhui Medical University, in accordance with the Chinese Guideline of Welfare and Ethics for Laboratory Animals, and conformed to the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (LLSC20221130).

Consent to Publication

This manuscript has not been published or presented elsewhere in part or in entirety and is not under consideration by another journal. All authors agree to the publication of this work.

Disclosure

The authors declare no competing interests.

Additional information

Funding

This study was funded by the Research Fund of Anhui Institute of Translational Medicine (No. ZHYX2020A003).