The Journal of antimicrobial chemotherapy · 2017
Baicalein acts as a nephroprotectant that ameliorates colistin-induced nephrotoxicity by activating the antioxidant defence mechanism of the kidneys and down-regulating the inflammatory response.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Dai Chongshan, Tang Shusheng, Wang Yang, Velkov Tony, Xiao Xilong
Аннотация
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-κB 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-1β and TNF-α 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-κB 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.
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-κB 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-1β and TNF-α 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-κB 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.