The effect of pirfenidone on rat chronic prostatitis/chronic pelvic pain syndrome and its mechanisms

Abstract

BackgroundChronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is an intractable problem of the urogenital system. The aetiopathogenesis and effective treatments for CP/CPPS are needed to be untangled. Pirfenidone is a molecule that exhibits anti‐inflammatory, antifibrotic, and antioxidative stress capacities in a variety of animal experiments and clinical trials. This study was aimed to investigate the therapeutic effect of pirfenidone on CP/CPPS and to identify the mechanism responsible for it.MethodsA CP/CPPS model was induced in rats by intraprostatic injection of complete Freund's adjuvant (CFA). Blood and prostatic tissues were harvested for assessment after the administration of pirfenidone or vehicle for 4 weeks.ResultsThe findings revealed that pirfenidone significantly ameliorated chronic pelvic pain and inhibited prostatic inflammation and fibrosis. Further study found that pirfenidone suppressed the expression of proinflammatory mediators, including tumor necrosis factor‐α, interleukin‐1β (IL‐1β), IL‐6, IL‐8. Pirfenidone exhibited a potent antioxidant capacity through improving the activities of glutathione, catalase, total superoxide dismutase, and reducing the production of malondialdehyde. Furthermore, pirfenidone also facilitated the polarization of M2 macrophages and suppressed the activation of the nuclear factor‐κB (NF‐κB) signaling pathway.ConclusionsPirfenidone can exert a beneficial effect against CFA‐induced CP/CPPS by anti‐inflammatory, antioxidative, antifibrotic properties, and the function is mediated at least partly through the M2 polarization of macrophages and the inhibition of NF‐κB signaling pathway. These findings suggest that pirfenidone holds promise as a potential therapeutic for the treatment of CP/CPPS.

Abnormal prostate microbiota composition is associated with experimental autoimmune prostatitis complicated with depression in rats

“…The prostatic stroma was hyperemic with edema present, and there were numerous inflammatory cells around the glandular cavity in the rates of the EAP and EAP+CUMS groups, which was congruent with previous reports (Chen et al, 2019). Proinflammatory cytokines are closely linked to the occurrence and development of CP/ CPPS and depression (Wang et al, 2018;Peng et al, 2020). Therefore, to confirm the occurrence of inflammation in the EAP rat model, proinflammatory cytokines in the prostate of the rats were detected.…”

Chronic Prostatitis: Impact of Lifestyle, Infection, and Inflammation on Semen Parameters

“…Increased levels of TNF-α in prostatic fluid and semen has been considered a marker of inflammation in chronic pelvic pain syndrome and chronic prostatitis; it activates the NF-κβ pathway inducing the expression of inflammatory factors such as TNF-α itself, IL-1β and IL-6, promoting hyperalgesia [4]; however, no increase in this cytokine was observed in the participants of this study, as well as, we did not observe an increase in the cytokines IL-8, IL-10, IL-1β, and TNF-α. which were reported elevated in chronic prostatitis by other authors [59], [69], [71].…”

“…IL-6 is a cytokine of great importance in inflammation, and it is responsible for increasing the production of IL-2. Both IL-6 and IL-2 are increased in serum and seminal plasma of patients with chronic pelvic pain syndrome [4], [59], [68], [69]. In animal models of chronic pelvic pain syndrome, infiltrating macrophages and CD4…”

Targeting Ferroptosis Attenuates Inflammation, Fibrosis, and Mast Cell Activation in Chronic Prostatitis

“…Inflammatory Grade Score. The inflammation grade was scored according to a four-point grading scale as described in previous studies [11,12]. In brief, the inflammatory cells were quantified by randomly counting on five spots under highpower fields (×400 magnification).…”