Oral administration of antimicrobial peptide MPX ameliorates orchitis and inflammatory damage in other organs

Abstract

Bacterial orchitis has a very high percentage of reproductive diseases in males. Therefore, specific medicines are urgently needed to prevent and treat orchitis. Antimicrobial peptides (AMPs) are widely recognized as one of the most promising substitutes for antibiotics. However, it is unknown whether AMPs play a key role in regulating the inflammation of male reproductive system. In the current study, mice were orally administered MPX (a member of Mastoparan family of AMPs, 0.5 mg/kg) for 20 and 40 days to evaluate the effect of AMPs on lipopolysaccharide (LPS)-induced testicular inflammation. We found that MPX could effectively improve the physiological function of the testes; upregulate the expression of androgen receptor (AR), inhibin subunit beta B (IBP) and SRY-related HMG box protein (SOX9); and promote sperm quantity and quality. Pathological analysis revealed that MPX significantly prevented LPS-induced inflammatory injury in mouse testes by decreasing the expression of inflammatory cytokines, such as interleukin-1β (IL-1β), IL-6, IL-18, tumor necrosis factor-α (TNF-α), and C-C motif chemokine ligand 2 (CCL2). These results suggest that MPX regulates the testicular inflammatory response by inhibiting the TLR4/NF-kappaB and p65 signaling pathway. Moreover, long-term feeding of MPX could significantly upregulate Bcl-2 and downregulate Bax and Caspase-3, thereby inhibiting LPS-induced apoptosis of testicular cells. In addition, long-term treatment with MPX could regulate LPS-induced pneumonia and enteritis. In summary, this research provides a detailed evaluation of the impact of long-term MPX feeding on inflammation in the male reproductive system, laying the groundwork for the development of specific medicines.