Affiliation:
1. Department of Children's Health Care, The First Affiliated Hospital of Nanjing Medical University Jiangsu Maternal and Child Health Care Hospital Nanjing China
2. Department of Nephrology Children's Hospital of Nanjing Medical University Nanjing China
3. Nanjing Key Laboratory of Pediatrics Children's Hospital of Nanjing Medical University Nanjing China
4. Jiangsu Key Laboratory of Pediatrics Nanjing Medical University Nanjing China
5. Department of Pediatrics Yancheng City No.1 People's Hospital Yancheng China
Abstract
AbstractNephrotoxicity is a major side effect of cisplatin. Apoptosis, oxidative stress, inflammation, and the MAPK signaling pathway activation are concerned with the pathophysiology of cisplatin‐induced acute kidney injury (AKI). Madecassoside (MA), an active constituent of Centella asiatica, has anti‐oxidative and anti‐inflammatory effects. The present research aim to investigate the underlying protective mechanisms of MA on cisplatin nephrotoxicity. Pretreatment of mice with MA markedly ameliorated cisplatin‐induced renal tubular cell injury evidenced by the improvement of kidney function and kidney morphology and blocked upregulation of kidney injury biomarkers (kidney injury molecule 1 (KIM‐1) and neutrophil gelatinase‐associated lipocalin (NGAL)). Cisplatin‐induced renal cell apoptosis, inflammation, and oxidative stress were also prevented by MA treatment. Consistent with the in vivo results, MA pretreatment attenuated cisplatin‐induced renal cell apoptosis, oxidative stress, and inflammation. Transcriptome analysis using RNA‐sequencing suggested that the MAPK signaling pathway was the most affected, and MA could inhibit cisplatin‐induced MAPK signaling pathway activation in vivo and in vitro. In summary, MA treatment ameliorated cisplatin‐induced renal tubular damage possibly by decreasing activation of the MAPK signaling pathway, suggesting its potential for the treatment of AKI.
Funder
National Natural Science Foundation of China
Subject
Health, Toxicology and Mutagenesis,Management, Monitoring, Policy and Law,Toxicology,General Medicine