Zinc Ameliorates Inflammation and Sperm Parameters in Rats With Experimental Autoimmune Prostatitis

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BACKGROUND: It is quite common for patients diagnosed with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) to have abnormal sperm parameters. Studies have shown that zinc ameliorates male sperm parameters and ameliorates prostatitis. OBJECTIVE: This study aims to investigate the effect of zinc on ameliorating ventral prostatitis in a rat model with experimental autoimmune prostatitis (EAP) by inhibiting the IKKβ/IκBα/NF-κB pathway mediated by inflammatory factors. It also aims to demonstrate that zinc treatment can attenuate a range of abnormal sperm parameters induced by experimental autoimmune prostatitis. METHODS: Sixteen rats were used to obtain the prostate antigen, and three groups of eight were used as experimental groups. The control group (NC group), the model group (EAP group), and the model + zinc group (EAPZ group). Following the official start of the experiment, the EAP was induced by multipoint intradermal immunization using a mixture containing 30 mg/ml prostate antigen and complete freund's adjuvant (CFA) on days 0 and 28 in the EAP and EAPZ groups, respectively. In contrast, the rats in the NC group were immunized with an equal volume mixture of normal saline and CFA at the same site and at the same time. After the model matured on day 42, rats in the EAPZ group received zinc gavage treatment (10 mg/kg/day) for 4 weeks. Rats in both the NC and EAP groups were given the same amount of normal saline by gavage. All rats were killed at 22 weeks of age. Prostate, epididymis, and serum were extracted from rats for further experiments. RESULTS: The study revealed that rats in the EAP group exhibited elevated levels of IL-1β, IL-6, and TNF-α in the ventral prostate lobe and higher expression levels of acid phosphatase (ACP) in serum. The total sperm count, viability, motility, and mitochondrial membrane potential (MMP) decreased significantly. Furthermore, serum zinc levels and ventral prostate zinc levels were reduced. Free zinc was also reduced in the ventral prostate and sperm of rats. The ventral prostate lobe tissues from EAP rats showed decreased protein expression of ZNT4, ZNT9, ZIP1, ZIP8, and ZIP14, while protein expression levels of IKKβ, IκBα, p-IκBα, p-NF-κB were increased. The overall data demonstrated damage to ventral prostate tissue, imbalance of zinc homeostasis, activation of inflammatory pathways, and impairment of sperm parameters in EAP rats. In the EAPZ group, there was a reduction in the expression levels of IL-1β, IL-6, and TNF-α. Conversely, sperm parameters and mitochondrial membrane potential exhibited an increase, while serum zinc and ventral prostate zinc levels demonstrated a rise. Additionally, the expression levels of the aforementioned zinc transporter and pathway proteins were restored. CONCLUSION: The above phenomena indicating that zinc supplementation could restore the balance of zinc homeostasis in the EAP rats, thereby reducing inflammation and damage to sperm parameters.

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