title: Paeonol alleviates epirubicin-induced renal injury in mice by regulating Nrf2 and NF-κB pathways.
abstract: Renal injury is a dose-dependent side effect of epirubicin that limits its clinical application in the field of tumor chemotherapy. Paeonol is an active ingredient with a variety of biological activities, including the prevention of multiple antineoplastic-induced toxicities. In the present study, we assessed the renoprotective effect of paeonol on epirubicin-induced nephrotoxicity and investigated the underlying mechanism. Renal function, kidney histology, oxidative stress, nitrative stress, inflammation, apoptotic proteins and the effects on signaling pathways were investigated. Paeonol lowered the levels of biomarkers of renal injury, relieved histopathological alterations, alleviated oxidative stress and nitrative stress, and ameliorated inflammation. Moreover, paeonol inhibited epirubicin-induced apoptosis by suppressing the activation of caspase-9 and caspase-3, the Bax/Bcl-2 imbalance and cytochrome c release. Further studies suggest that paeonol up-regulates the Nrf2/HO-1 pathway by increasing the expression of Nrf2 and HO-1 and down-regulates the NF-κB pathway by reducing IκBα degradation and blocking the p-NF-κB nuclear translocation. In conclusion, paeonol alleviates epirubicin-induced renal injury in mice by regulating the Nrf2 and NF-κB signaling pathways.
authors.affiliation: Department of Pharmacy, The Second Hospital of Shandong University, Jinan, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Neurology, The Second Hospital of Shandong University, Jinan, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Pharmacy, The Second Hospital of Shandong University, Jinan, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Sun
authors.affiliation: Department of Pharmacy, The Second Hospital of Shandong University, Jinan, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, The Second Hospital of Shandong University, Jinan, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pharmacy, The Second Hospital of Shandong University, Jinan, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Pharmacy, The Second Hospital of Shandong University, Jinan, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, The Second Hospital of Shandong University, Jinan, China. Electronic address: sundq0405@126.com.
authors.forename: Deqing
authors.initials: D
authors.lastname: Sun
mesh_terms: D000098:Acetophenones / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects*; D015251:Epirubicin / Q000633:toxicity*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007668:Kidney / Q000166:cytology / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D051996:Transcription Factor RelA / Q000378:metabolism*
chemical_list: D000098:Acetophenones; D000975:Antioxidants; D051267:NF-E2-Related Factor 2; D051996:Transcription Factor RelA; C013638:paeonol; D015251:Epirubicin
keywords: Epirubicin; NF-κB; Nephrotoxicity; Nrf2; Paeonol