The protective effects of Zhen-Wu-Tang against cisplatin-induced acute kidney injury in rats

• Published in: PloS one 2017-06, Vol.12 (6), p.e0179137-e0179137
• Main Authors: Liu, Qi, Hu, Shouyu, He, Yi, Zhang, Jiashu, Zeng, Xiaona, Gong, Fengtao, Liang, Li'na
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; Aberration; Actin; Acute Kidney Injury - chemically induced; Acute Kidney Injury - drug therapy; Acute Kidney Injury - pathology; AKT protein; Animals; Apoptosis; Apoptosis - drug effects; Bax protein; beta Catenin - biosynthesis; Biology and Life Sciences; Blood; Blood Urea Nitrogen; Bone morphogenetic proteins; Caspase; Caspase-3; Chemotherapy; Chinese medicine; Chronic kidney failure; Cisplatin; Cisplatin - adverse effects; Collagen; Creatinine; Creatinine - urine; Death; Deposition; Development and progression; Diabetes; Dosage and administration; Drug dosages; Drugs, Chinese Herbal - administration & dosage; Exposure; Extracellular matrix; Fibrosis; Fibrosis - chemically induced; Fibrosis - drug therapy; Fibrosis - pathology; Gene Expression Regulation - drug effects; Growth factors; Health aspects; Humans; Immunoglobulins; Injection; Injuries; Kidney diseases; Kidney transplantation; Kidneys; Laboratory animals; Medicine and Health Sciences; Mortality; NF-E2-Related Factor 2 - biosynthesis; Nitrogen; Patient outcomes; Pharmaceutical sciences; Pharmacy; Phosphorylation; Rats; Research and Analysis Methods; Risk factors; Rodents; Signal transduction; Smooth muscle; Staining; Tissues; Transforming Growth Factor beta1 - biosynthesis; Transforming growth factor-b; Transforming growth factors; Urea; Western blotting; β-Catenin
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0179137

Acute kidney injury (AKI) is a common clinical condition that confers a risk of progression of chronic kidney disease and a high risk of death. The purpose of the current study is to investigate the anti-apoptotic and anti-fibrotic effects of Zhen-Wu-Tang (ZWT) on cisplatin (CIS)-induced renal injury and elucidate the involvement of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), the PI3K/Akt signaling pathway, transforming growth factor (TGF)-β and the Wnt/β-catenin signaling pathway in the positive effects of Zhen-Wu-Tang on the kidneys. Wistar rats were randomly assigned into six groups of 6 rats each as follows: normal control 1; normal control 2; CIS 1 and CIS 2, which received single intraperitoneal injections of CIS (6 mg/kg); CIS+ZWT 4 and CIS+ZWT 10, which received ZWT (1 ml/100 g/day, ig) starting days after the CIS injection for 4 and 10 days, respectively. Hematoxylin-eosin (H&E) staining was performed to identify the amelioration of histopathological changes in the kidneys and apoptosis of the renal proximal tubular cells. Picrosirius red staining was used to evaluate renal fibrosis after ZWT treatment. The relationship between ZWT and the upregulation of Nrf2, phosphorylation of Akt, and the downregulation of TGF-β and WNT/β-catenin were determined by Western blotting. At the end of the experiment, serum was isolated from the orbital blood of rats, and blood urea nitrogen (BUN) and creatinine (Cr) levels were measured. The results showed that ZWT restored the histological alterations, aberrant collagen deposition in the kidneys and the BUN and Cr levels that were increased by CIS. Treatment with ZWT reduced the expression levels of TGF-β and Wnt and increased the expression levels of Nrf2, PI3K and Akt in the CIS-exposed kidney tissues. Furthermore, ZWT downregulated apoptosis and fibrosis by modulating the expression levels of caspase-3, Bax and alpha-smooth muscle actin (α-SMA). In conclusion, this study provides evidence for the anti-fibrotic and anti-apoptotic roles of ZWT in CIS-induced experimental kidney injury.