Melatonin ameliorates inflammation and oxidative stress by suppressing the P38MAPK signaling pathway in LPS-induced sheep orchitis

Shou Long Deng, Bao Lu Zhang, Russel J. Reiter, Yi Xun Liu

Research output: Contribution to journalArticlepeer-review

Abstract

Gram-negative bacterial infections of the testis can lead to infectious orchitis, which negatively influences steroid hormone synthesis and spermatogenesis. Lipopolysaccharide (LPS), a major component of the Gram-negative bacterial cell wall, acts via toll like receptors 4 (TLR4) to trigger innate immune responses and activate nuclear factor kappa B signaling. The protective mechanisms of melatonin on LPS-induced infectious orchitis have not been reported. Herein, we developed an LPS-induced sheep infectious orchitis model. In this model, the phagocytic activity of testicular macrophages (TM) was enhanced after melatonin treatment. Moreover, we found that melatonin suppressed secretion of TM pro-inflammatory factors by suppressing the p38MAPK pathway and promoting Leydig cell testosterone secretion. Expressions of GTP cyclohydrolase-I and NADPH oxidase-2 were reduced by melatonin while heme oxygenase-1 expression was up-regulated. Thus, melatonin reduced the severity of LPS-induced orchitis by stimulating antioxidant activity. The results of this study provide a reference for the treatment of acute infectious orchitis.

Original languageEnglish (US)
Article number1277
Pages (from-to)1-17
Number of pages17
JournalAntioxidants
Volume9
Issue number12
DOIs
StatePublished - Dec 2020

Keywords

  • Melatonin
  • P38MAPK
  • Sheep
  • TLR4
  • Testicular macrophages

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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