Background: Chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS) leads to severe discomfort in males and loss of sperm quality. Current therapeutic options have failed to achieve satisfactory results. Sodium butyrate (NaB) plays a beneficial role in reducing inflammation, increasing antioxidant capacities, and improving organ dysfunction; additionally NaB has good safety prospects and great potential for clinical application. The purpose of the current research was to study the effect of NaB on CP/CPPS and the underlying mechanisms using a mouse model of experimental autoimmune prostatitis (EAP) mice.
Methods: The EAP mouse model was successfully established by subcutaneously injecting a mixture of prostate antigen and complete Freund's adjuvant. Then, EAP mice received daily intraperitoneal injections of NaB (100, 200, or 400 mg/kg/day) for 16 days, from Days 26 to 42. We then explored anti-inflammatory potential mechanisms of NaB by studying the effects of Nrf2 inhibitor ML385 and HO-1 inhibitor zinc protoporphyrin on prostate inflammation and pelvic pain using this model. On Day 42, 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 levels of inflammation-related cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor were detected by enzyme-linked immunosorbent assay. The regulation of Nrf2/HO-1 signaling pathway and the expression of NLRP3 inflammasome-related protein in EAP mice were detected by western blot analysis assay.
Results: Compared with the EAP group, chronic pain development, histological manifestations, and cytokine levels showed that NaB reduced the severity of EAP. NaB treatment could inhibit NLRP3 inflammasome activation. Mechanism studies showed that NaB intervention could alleviate oxidative stress in EAP mice through Nrf2/HO-1 signal pathway. Nrf2/HO-1 pathway inhibitors can inhibit NaB -mediated oxidative stress. The inhibitory effect of NaB on the activation of NLRP3 inflammasome and anti-inflammatory effect can also be blocked by Nrf2/HO-1 pathway.
Conclusions: NaB treatment can alleviates prostatic inflammation and pelvic pain associated with EAP by inhibiting oxidative stress and NLRP3 inflammasome activation via the Nrf2/HO-1 pathway. NaB has the potential as an effective agent in the treatment of EAP.
Keywords: NLRP3 inflammasome; chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS); inflammation; oxidative stress; sodium butyrate.
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