期刊
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
卷 72, 期 9, 页码 2562-2569出版社
OXFORD UNIV PRESS
DOI: 10.1093/jac/dkx185
关键词
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资金
- Key Projects in Chinese National Science and Technology Pillar Program during the 12th Five-year Plan Period [2015BAD11B03]
- National Natural Science Foundation of China [31422055]
- National Institute of Allergy and Infectious Diseases of the National Institutes of Health [R01 AI111965]
- Australian National Health and Medical Research Council (NHMRC)
Background: Nephrotoxicity is the major adverse effect patients experience during colistin therapy. The development of effective nephroprotective agents that can be co-administered during polymyxin therapy remains a priority area in antimicrobial chemotherapy. Objectives: To investigate the nephroprotective effect of baicalein, a component of the root of Scutellaria baicalensis, against colistin-induced nephrotoxicity using a mouse model. Methods: C57BL/6 mice were randomly divided into the following groups: control, baicalein 100 mg/kg/day (administered orally), colistin (18 mg/kg/day administered intraperitoneally) and colistin (18 mg/kg/day) plus baicalein (25, 50 and 100 mg/kg/day). After 7 day treatments, histopathological damage, the markers of renal functions, oxidative stress and inflammation were examined. The expressions of Nrf2, HO-1 and NF-kappa B mRNAs were also further examined using quantitative RT-PCR examination. Results: Baicalein co-administration markedly attenuated colistin-induced oxidative and nitrative stress, apoptosis, the infiltration of inflammatory cells, and caused decreases in IL-1 beta and TNF-alpha levels (all P<0.05 or 0.01) in the kidney tissues. Baicalein co-administration up-regulated expression of Nrf2 and HO-1 mRNAs and down-regulated the expression of NF-kappa B mRNA, compared with those in the colistin alone group. Conclusions: To the best of our knowledge, this is the first study demonstrating the protective effect of baicalein on colistin-induced nephrotoxicity and apoptosis by activating the antioxidant defence mechanism in kidneys and down-regulating the inflammatory response. Our study highlights that oral baicalein could potentially ameliorate nephrotoxicity in patients undergoing polymyxin therapy.
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