Baicalein, a Bioflavonoid, Prevents Cisplatin-Induced Acute Kidney Injury by Up-Regulating Antioxidant Defenses and Down-Regulating the MAPKs and NF-κB Pathways

Abstract

Acute renal failure is a serious complication of the anticancer drug cisplatin. The potential role of baicalein, a naturally occurring bioflavonoid on cisplatin-induced renal injury is unknown. Here, we assessed the effect of baicalein against a murine model of cisplatin-induced acute renal failure and investigated the underlying possible mechanisms. Renal function, kidney histology, inflammation, oxidative stress, renal mitochondrial function, proteins involved in apoptosis, nuclear translocation of Nrf2 and effects on intracellular signaling pathways such as MAPKs, and NF-κB were assessed. Pretreatment with baicalein ameliorated the cisplatin-induced renal oxidative stress, apoptosis and inflammation and improved kidney injury and function. Baicalein inhibited the cisplatin-induced expression of iNOS, TNF-α, IL-6 and mononuclear cell infiltration and concealed redox-sensitive transcription factor NF-κB activation via reduced DNA-binding activity, IκBα phosphorylation and p65 nuclear translocation in kidneys. Further studies demonstrated baicalein markedly attenuated cisplatin-induced p38 MAPK, ERK1/2 and JNK phosphorylation in kidneys. Baicalein also restored the renal antioxidants and increased the amount of total and nuclear accumulation of Nrf2 and downstream target protein, HO-1 in kidneys. Moreover, baicalein preserved mitochondrial respiratory enzyme activities and inhibited cisplatin-induced apoptosis by suppressing p53 expression, Bax/Bcl-2 imbalance, cytochrome c release and activation of caspase-9, caspase-3 and PARP. Our findings suggest that baicalein ameliorates cisplatin-induced renal damage through up-regulation of antioxidant defense mechanisms and down regulation of the MAPKs and NF-κB signaling pathways.

Paeonol alleviates epirubicin-induced renal injury in mice by regulating Nrf2 and NF-κB pathways

“…The proposed mechanism of anthracycline-induced organ damage includes the generation of reactive oxygen species, inflammation, caspase activation and apoptosis (Sahu et al, 2014(Sahu et al, , 2015. Our previous research has suggested that the activation of the nuclear factor-κB (NF-κB) pathway is involved in the development and progression of epirubicin-induced hepatotoxicity and reactive oxygen species play a crucial role in aggravating inflammation by activating the NF-κB pathway (Wu et al, 2016).…”

Regulation of cytotoxicity and apoptosis-associated pathways contributes to the enhancement of efficacy of cisplatin by baicalein adjuvant in human A549 lung cancer cells

“…However, there are numerous side effects associated with this type of treatment (5). Baicalein has been proposed in several extensive studies as a potential candidate for the treatment of cancer (14,15,18). In the present study, the effect of cisplatin combined with baicalein (a flavonoid component isolated from the root of traditional Chinese medicine SB) on cytotoxicity and apoptosis of human lung cancer cells A549 was examined.…”

“…SB is currently recognized as a novel anti-cancer drug and chemotherapy adjuvant (10)(11)(12). Baicalein is one of the bioactive flavonoid components isolated from the root of SB, and it has been revealed to account for the majority of cytotoxicity of SB for a range of cancer cell lines in vitro (13)(14)(15). Molecular studies in other human cell lines have demonstrated that these flavonoid compounds possess potent cell cycle arresting and apoptotic properties (13,16).…”

Baicalein and its underlying mechanism as a protector against liver injury induced by cisplatin in mice

“…It is reported that baicalein increases the cytotoxicity of cisplatin [18]. It has also been demonstrated that baicalein prevents cisplatin-induced renal damage in mice [19]. However, to the best of our knowledge, the effect of baicalein in hepatoprotection during cisplatin administration has not been reported so far.…”