Li-ESWT treatment reduces inflammation, oxidative stress, and pain via the PI3K/AKT/FOXO1 pathway in autoimmune prostatitis rat models

Abstract

Background: Due to limited data on the pathogenesis of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and the suboptimal therapeutic effect, the development of new and effective treatment modalities was needed urgently. Low-intensity extracorporeal shock wave therapy (Li-ESWT) has been reported for the treatment of CP/CPPS. However, the underlying mechanism remains to be elucidated.

Objective: To interrogated the efficacy and the mechanism of Li-ESWT in the treatment of CP/CPPS.

Materials and methods: According to different treatments, RWPE-1 cells (human prostate epithelial cells) were randomly divided into three groups: control group, LPS (lipopolysaccharide) group, or Li-ESWT group (LPS-induced RWPE-1 managed by Li-ESWT). Following the Li-ESWT treatment, the levels of oxidative stress were assayed. We then established a rat model of experimental autoimmune prostatitis (EAP) by injecting prostatic protein homogenate mixed with complete Freund's adjuvant. The Sprague-Dawley rats were randomly divided into the control group, EAP group, or Li-ESWT group. Von Frey Filament was used to quantify pelvic hyperalgesia in the rats. Prostates tissues from each group were collected for immunohistochemistry, oxidation stress, and Western blot analysis.

Results: Histological analysis showed reduced inflammation and expression of cytokines (TNF-α, IL-1β, IL-6, COX-2, SP) in prostate tissues from the Li-ESWT group compared with those from the EAP group (all p < 0.05). Similarly, there was reduced pelvic pain and allergic symptoms in the Li-ESWT group compared with the EAP group (all p < 0.05). Besides, Li-ESWT treatment could decrease oxidative stress in the prostate and in RWPE-1 cells, respectively (both p < 0.05). Moreover, the Li-ESWT upregulated the expression of CAT through the inhibition of phosphorylation of AKT/FOXO1 signaling pathway.

Discussion and conclusions: Li-ESWT may reduce inflammation, oxidative stress, and pain in rats with autoimmunity-induced prostatitis via the PI3 K/AKT/FOXO1 pathway. It implies that Li-ESWT can present a potential therapeutic option for the treatment of CP/CPPS.

Keywords: EAP-rat; chronic pelvic pain syndrome; chronic prostatitis; inflammation; low-intensity extracorporeal shock wave therapy; oxidation stress.