Melatonin pretreatment alleviates blast-induced oxidative stress in the hypothalamic-pituitary-gonadal axis by activating the Nrf2/HO-1 signaling pathway

• Published in: Life sciences (1973) 2021-09, Vol.280, p.119722, Article 119722
• Main Authors: Zhang, Yin, Cong, Peifang, Tong, Changci, Jin, Hongxu, Liu, Yunen, Hou, Mingxiao
• Format: Article
• Language: English
• Subjects: Abnormalities; Animals; Antioxidants; Antioxidants - pharmacology; Antioxidants - therapeutic use; Apoptosis; Bax protein; Bcl-2 protein; Blast Injuries - drug therapy; Blast Injuries - metabolism; Blast Injuries - pathology; Blast injury; Caspase-3; Enzyme-linked immunosorbent assay; Experiments; Heme Oxygenase-1 - metabolism; Homeostasis; Hypothalamic-pituitary-gonadal axis; Hypothalamo-Hypophyseal System - drug effects; Hypothalamo-Hypophyseal System - metabolism; Hypothalamo-Hypophyseal System - pathology; Hypothalamus; Inflammation; Interleukin 10; Male; Melatonin; Melatonin - pharmacology; Melatonin - therapeutic use; Melatonin receptor; Mice; Mice, Inbred C57BL; NF-E2-Related Factor 2 - metabolism; NF-κB protein; Nrf2/HO-1; Oxidative stress; Oxidative Stress - drug effects; Pituitary; Pituitary-gonadal axis; Pretreatment; Rats; Rats, Sprague-Dawley; Signal transduction; Signal Transduction - drug effects; Signaling; Testis - drug effects; Testis - metabolism; Testis - pathology
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2021.119722

Although melatonin has been demonstrated to exert a potent antioxidant effect, the ability of melatonin to alleviate blast-induced oxidative stress in the hypothalamic-pituitary-gonadal (HPG) axis remains unclear. This study aimed to elucidate the effects and underlying mechanism of melatonin pretreatment on the HPG axis disrupted by blast injury. Sixty C57BL/6 mice were randomly divided into control, blast, and blast + melatonin groups for behavioral experiments. The elevated maze experiment, open field experiment, and Morris Water Maze experiment were carried out on the 7th, 14th and 28th day after the blast injury. Fifty Sprague Dawley rats were randomly divided into control, blast, blast + melatonin, and blast + melatonin + luzindole groups for hormone assays and molecular and pathological experiments. Blood samples were used for HPG axis hormone detection and ELISA assays, and tissue samples were used to detect oxidative stress, inflammation, apoptosis, and stress-related protein levels. The results showed that melatonin pretreatment alleviated blast-induced behavioral abnormalities in mice and maintained the HPG axis hormone homeostasis in rats. Additionally, melatonin significantly reduced MDA5 expression and increased the expression of Nrf2/HO-1. Moreover, melatonin significantly inhibited NF-κB expression and upregulated IL-10 expression, and it reversed the blast-induced high expression of caspase-3 and Bax and the low expression of Bcl-2. Furthermore, luzindole counteracted melatonin inhibition of NF-κB and upregulated Nrf2/HO-1. Melatonin significantly alleviated blast-induced HPG axis hormone dyshomeostasis, behavioral abnormalities, oxidative stress, inflammation, and apoptosis, which may be achieved by upregulating the Nrf2/HO-1 signaling pathway. Our study suggested that melatonin pretreatment is a potential treatment for blast-induced HPG axis hormonal and behavioral abnormalities. •Melatonin alleviates blast-induced HPG axis hormonal and behavioral abnormalities.•Melatonin significantly improved the expression of Nrf2/HO-1.•Anti-inflammatory and antioxidant effects of melatonin were inhibited by luzindole.