PMID- 33327643 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201229 IS - 2076-3921 (Print) IS - 2076-3921 (Electronic) IS - 2076-3921 (Linking) VI - 9 IP - 12 DP - 2020 Dec 14 TI - Melatonin Ameliorates Inflammation and Oxidative Stress by Suppressing the p38MAPK Signaling Pathway in LPS-Induced Sheep Orchitis. LID - 10.3390/antiox9121277 [doi] LID - 1277 AB - 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. FAU - Deng, Shou-Long AU - Deng SL AD - CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China. FAU - Zhang, Bao-Lu AU - Zhang BL AD - Marine Consulting Center of Natural Resources of the People's Republic of China, Beijing 100071, China. FAU - Reiter, Russel J AU - Reiter RJ AD - Department of Cell Systems and Anatomy, UT Health San Antonio, San Antonio, TX 78229, USA. FAU - Liu, Yi-Xun AU - Liu YX AD - State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China. LA - eng PT - Journal Article DEP - 20201214 PL - Switzerland TA - Antioxidants (Basel) JT - Antioxidants (Basel, Switzerland) JID - 101668981 PMC - PMC7765110 OTO - NOTNLM OT - TLR4 OT - melatonin OT - p38MAPK OT - sheep OT - testicular macrophages COIS- The authors declare no conflict of interest. EDAT- 2020/12/18 06:00 MHDA- 2020/12/18 06:01 PMCR- 2020/12/14 CRDT- 2020/12/17 01:03 PHST- 2020/11/23 00:00 [received] PHST- 2020/12/10 00:00 [revised] PHST- 2020/12/11 00:00 [accepted] PHST- 2020/12/17 01:03 [entrez] PHST- 2020/12/18 06:00 [pubmed] PHST- 2020/12/18 06:01 [medline] PHST- 2020/12/14 00:00 [pmc-release] AID - antiox9121277 [pii] AID - antioxidants-09-01277 [pii] AID - 10.3390/antiox9121277 [doi] PST - epublish SO - Antioxidants (Basel). 2020 Dec 14;9(12):1277. doi: 10.3390/antiox9121277.