Abstract
Cisplatin is a commonly used chemotherapeutic agent in the treatment of different types of malignant tumors, but nephrotoxicity limits its usage. Therefore, in this study, we aimed to determine the possible protective effect of Huaiqihuang (HQH) extractum, a kind of Chinese herbal complex that consists of Trametes robiniophila Murr., Lycium barbarum and Polygonatum sibiricum, against nephrotoxicity induced by cisplatin in mice. We found that pretreatment with HQH significantly attenuated the cisplatin-induced increase in blood urea nitrogen (BUN), interstitial congestion, acute renal tubular injury and tubular cell apoptosis and necroptosis. It was further shown that HQH administration reduced cisplatin-induced release and nuclear-cytoplasmic translocation of HMGB1 and inactivated its downstream signaling molecules, TLR4 and NFκB, in renal tubular cells; as a result, HQH repressed cisplatin-induced TNF-α production. As dexamethasone (Dex) exerts renoprotective effects in severe Acute kidney injury (AKI), we compared it with HQH and found that HQH showed similar renoprotective effects to dexamethasone via similar mechanisms. Considering the potential side effects of corticosteroids, reducing the effectiveness of treatment and shortening survival in solid tumor patients, we suggest administration of HQH as a potential adjuvant for cisplatin therapy in solid tumor patients to preserve renal function.
Highlights
Cisplatin is a widely used anti-cancer agent that has been used in non-small cell lung, esophagus, bladder, endometrium, ovary and testicular cancers, as well as many other types of cancers[1,2]
The renoprotective effects of HQH against cisplatin-induced Acute kidney injury (AKI) was surveyed in mice and we found that pretreatment with HQH demonstrated renoprotective effects similar to those of Dex via similar mechanisms to relieve cisplatin-induced renal injury
Urea levels were significantly increased in the cisplatin-treated group, but this effect was significantly reversed by HQH and Dex pretreatment (Fig. 1B)
Summary
Cisplatin is a widely used anti-cancer agent that has been used in non-small cell lung, esophagus, bladder, endometrium, ovary and testicular cancers, as well as many other types of cancers[1,2]. Liu H et al reported that HQH extractum could increase podocyte nephrin expression, inhibit the NF-κB signaling pathway and suppress glomerular and tubular apoptosis in rats with adriamycin-induced nephropathy[22]. All these studies suggest that HQH extractum is a potent nephroprotective agent; little is known about the protective effect of HQH in AKI. It was shown that HQH did not impair cisplatin-mediated killing of HeLa tumor cells in vitro Taken together, these results suggest that HQH is a potent renoprotective agent for preventing the renal toxicity caused by cisplatin without affecting the anti-tumor effects of cisplatin
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