Pretreatment of Huaiqihuang extractum protects against cisplatin-induced nephrotoxicity

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.

The Effect of Chinese Traditional Medicine Huaiqihuang (HQH) on the Protection of Nephropathy

“…According to Liu et al, HQH was found to downregulate the expression of proapoptotic proteins Bax, Cyt C, and caspase 3 and upregulate the expression of antiapoptotic proteins Bcl-2 [9]. Similarly, Fang et al found that, compared with the control group, the proportion of proapoptotic and antiapoptotic proteins in the HP-1 treatment group has a relatively balanced ratio and the apoptosis was reduced accordingly [8,37]. Furthermore, GRP78 can bind and inhibit the activity of proapoptotic protein BIK on endoplasmic reticulum [38], promoting the expression of bcl-2 so as to inhibit cell apoptosis [39,40].…”

“…Liu et al demonstrated that Huaier inhibits the expression of TNF-α, p-NF-κB p65, and IκB, thereby inhibiting the apoptotic NF-κB signaling pathway and protecting the kidney [9]. Guo et al found that in CP-induced nephropathy, Huaier can reduce the TLR4/NF-κB pathway to protect the kidneys [37]. Adding Huaier to CP-induced nephropathy, it was found that it can downregulate the PI3K/Akt/m-TOR/NF-κB signaling pathway in cisplatin nephrotoxicity cells and downregulate the expression of p-NF-κB.…”

“…Renal interstitial fibrosis (RIF) is characterized by the expression of inflammatory cells and the accumulation of collagen components in the renal interstitial, atrophy and dilatation of renal tubules, capillary reduction around the tubules, and progressive destruction of the nephron. Renal interstitial fibrosis eventually leads to renal failure [4,10,37,42,66].…”

“…Cisplatin (CP) is a commonly used chemotherapy drug for the treatment of malignant tumors. But various side effects such as nephrotoxicity, ototoxicity, and neurotoxicity, affecting its efficacy [37]. Liang et al investigated that Huaier can reduce the levels of oxidative stress, inflammation, and mitochondrial dysfunction, thereby reducing kidney damage.…”

“…Reduces proteinuria by enhancing nephrin expression and inhibit the NF-κB signaling pathway, interferes with the proinflammatory and proapoptotic signaling, and promotes the nephrin and podocin protein expression [11,66,73] Renal interstitial fibrosis Reduces infiltration of myofibroblast and downregulates the expression of α-SMA [4,66] Allergic purpura nephritis Downregulates the expression of TGF-β1 mRNA and upregulates the expression of nephrin and podocin on the septal septum [65] Cisplatin nephrotoxicity Inhibits cp-induced renal tubular apoptosis and cell cycle arrest and reduces the levels of oxidative stress, inflammation and mitochondrial dysfunction [8,37] IgA nephropathy Increases the expression of nephrin and improves the anomalies of their distribution and improves the expression of CD3, CD4, and CD4/CD8 [14,64] Renal carcinoma…”