期刊
BIOMOLECULES
卷 10, 期 1, 页码 -出版社
MDPI
DOI: 10.3390/biom10010011
关键词
melatonin; aristolochic acid; nephropathy; oxidative stress; inflammation; apoptosis; fibrosis
资金
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Science and ICT & Future Planning (MSIP) [NRF-2017R1E1A2A02023467, NRF-2017R1C1B5076755]
- Ministry of Education [NRF-2017R1D1A1B03035278]
Melatonin, a pineal hormone, is well known to regulate the sleep-wake cycle. Besides, the hormone has been shown to display pleiotropic effects arising from its powerful anti-oxidant and anti-inflammatory activities. Recent studies have reported that melatonin exerts protective effects in animal models of kidney disease. However, the potential effects of melatonin on aristolochic acid (AA)-induced nephropathy (AAN) have not yet been investigated. Here, we found that the administration of melatonin ameliorated AA-induced renal dysfunction, as evidenced by decreased plasma levels of blood urea nitrogen and creatinine and histopathological abnormalities such as tubular dilatation and cast formation. The upregulation of tubular injury markers after AA injection was reversed by melatonin. Melatonin also suppressed AA-induced oxidative stress, as evidenced by the downregulation of 4-hydroxynonenal and reduced level of malondialdehyde, and modulated expression of pro-oxidant and antioxidant enzymes. In addition, p53-dependent apoptosis of tubular epithelial cells, infiltration of macrophages and CD4(+) T cells into damaged kidneys, and renal expression of cytokines and chemokines were inhibited by melatonin. Moreover, melatonin attenuated AA-induced tubulointerstitial fibrosis through suppression of the tumor growth factor-beta/Smad signaling pathway. These results suggest that melatonin might be a potential therapeutic agent for AAN.
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