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.

• Authors: Yujiao Guo, Meng Wang, Jingyi Mou, Zhi Zhao, Juan Yang, Fengming Zhu, Guangchang Pei, Han Zhu, Yuxi Wang, Gang Xu, Rui Zeng, Ying Yao
• Journal: Scientific reports (Sci Rep) Vol. 8 Issue 1 Pg. 7333 (05 09 2018) ISSN: 2045-2322 [Electronic] England
• PMID: 29743526 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Drugs, Chinese Herbal
• HMGB1 Protein
• HMGB1 protein, mouse
• NF-kappa B
• Protective Agents
• Tlr4 protein, mouse
• Toll-Like Receptor 4
• Tumor Necrosis Factor-alpha
• huai qi huang
• Cisplatin

Topics

• Acute Kidney Injury (pathology, prevention & control)
• Animals
• Apoptosis (drug effects)
• Blood Urea Nitrogen
• China
• Cisplatin (adverse effects, pharmacology)
• Disease Models, Animal
• Drugs, Chinese Herbal (metabolism, pharmacology)
• HMGB1 Protein (metabolism)
• Kidney (metabolism)
• Lycium (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• NF-kappa B (metabolism)
• Polygonatum (metabolism)
• Protective Agents (pharmacology)
• Signal Transduction (drug effects)
• Toll-Like Receptor 4 (metabolism)
• Trametes (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)