Sappanone A protects mice against cisplatin-induced kidney injury.
Cisplatin (CP) is an anti-cancer drug that often causes nephrotoxicity due to enhanced inflammatory response and oxidative stress. Sappanone A (SA), a homoisoflavanone isolated from the heartwood of Caesalpinia sappan, has been known to have antioxidant and anti-inflammatory effects. In this study, we aimed to investigate the protective effects and mechanism of SA on CP-induced kidney injury in mice. The results showed that treatment of SA improved CP-induced histopathalogical injury and renal dysfunction. SA also inhibited CP-induced MPO, MDA, TNF-α and IL-1β production and up-regulated the activities of SOD and GSH-PX decreased by CP. SA significantly inhibited the apoptosis rate of kidney tissues induced by CP. Furthermore, SA was found to inhibit CP-induced NF-κB activation. Treatment of SA up-regulated the expression of Nrf2 and HO-1 in a dose-dependent manner. In vitro, SA dose-dependently inhibited CP-induced TNF-α and IL-1β production and NF-κB activation in HK-2 cells. In conclusion, these results suggested that SA inhibited CP-induced kidney injury through activating Nrf2 and inhibiting NF-κB activation. SA was a potential therapeutic drug for treating CP-induced kidney injury.
Department of Pathology, Hebei Medical University, Shijiazhuang, Hebei 050017, China; Department of Pathology, Heibei General Hospital, Shijiazhuang, Hebei 050051, China.
Lin
L
Kang
Department of Pathology, Heibei General Hospital, Shijiazhuang, Hebei 050051, China.
Huanfen
H
Zhao
Department of Pathology, Heibei General Hospital, Shijiazhuang, Hebei 050051, China.
Chen
C
Chen
Department of Pathology, Heibei General Hospital, Shijiazhuang, Hebei 050051, China.
Xiuzhi
X
Zhang
Department of Pathology, Heibei General Hospital, Shijiazhuang, Hebei 050051, China.
Mingtang
M
Xu
Department of Pathology, Hebei Medical University, Shijiazhuang, Hebei 050017, China. Electronic address: duanhuijun33@sina.com.
Huijun
H
Duan
D000818:Animals; D029911:Caesalpinia; D002460:Cell Line; D002945:Cisplatin / Q000009:adverse effects* / Q000627:therapeutic use; D064420:Drug-Related Side Effects and Adverse Reactions / Q000517:prevention & control*; D006801:Humans; D007529:Isoflavones / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
D007529:Isoflavones; D016328:NF-kappa B; C000601074:sappanone A; D002945:Cisplatin
Cisplatin; Kidney; NF-κB; Sappanone A