Natural products: potential treatments for cisplatin-induced nephrotoxicity

• Published in: Acta pharmacologica Sinica Vol. 42; no. 12; pp. 1951 - 1969
• Main Authors: Fang, Chun-yan, Lou, Da-yong, Zhou, Li-qin, Wang, Jin-cheng, Yang, Bo, He, Qiao-jun, Wang, Jia-jia, Weng, Qin-jie
• Format: Journal Article
• Language: English
• Published: Singapore Springer Nature Singapore 01-12-2021; Nature Publishing Group; Springer Singapore
• Subjects: Acute Kidney Injury - chemically induced; Acute Kidney Injury - drug therapy; Acute Kidney Injury - etiology; Acute Kidney Injury - prevention & control; Animals; Antineoplastic Agents - toxicity; Antioxidants; Antitumor agents; Apoptosis; Apoptosis - drug effects; Biological Products - therapeutic use; Biomedical and Life Sciences; Biomedicine; Breast cancer; Chemotherapy; Cisplatin; Cisplatin - toxicity; Flavonoids; Head and neck; Humans; Immunology; Inflammation; Inflammation - drug therapy; Internal Medicine; Kidney - drug effects; Kidney diseases; Kidneys; Lung cancer; Medical Microbiology; Molecular modelling; Natural products; Nephropathy; Ovarian cancer; Oxidative stress; Oxidative Stress - drug effects; Pharmacology/Toxicology; Phenylpropanoids; Polysaccharides; Protective Agents - therapeutic use; Renal failure; Renal function; Review; Review Article; Saponins; Uremia; Vaccine; natural products; anti-apoptosis; antioxidant; nephrotoxicity; acute kidney injury; anti-inflammation; cisplatin; nephroprotection
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1038/s41401-021-00620-9

Cisplatin is a clinically advanced and highly effective anticancer drug used in the treatment of a wide variety of malignancies, such as head and neck, lung, testis, ovary, breast cancer, etc. However, it has only a limited use in clinical practice due to its severe adverse effects, particularly nephrotoxicity; 20%–35% of patients develop acute kidney injury (AKI) after cisplatin administration. The nephrotoxic effect of cisplatin is cumulative and dose dependent and often necessitates dose reduction or withdrawal. Recurrent episodes of AKI result in impaired renal tubular function and acute renal failure, chronic kidney disease, uremia, and hypertensive nephropathy. The pathophysiology of cisplatin-induced AKI involves proximal tubular injury, apoptosis, oxidative stress, inflammation, and vascular injury in the kidneys. At present, there are no effective drugs or methods for cisplatin-induced kidney injury. Recent in vitro and in vivo studies show that numerous natural products (flavonoids, saponins, alkaloids, polysaccharide, phenylpropanoids, etc.) have specific antioxidant, anti-inflammatory, and anti-apoptotic properties that regulate the pathways associated with cisplatin-induced kidney damage. In this review we describe the molecular mechanisms of cisplatin-induced nephrotoxicity and summarize recent findings in the field of natural products that undermine these mechanisms to protect against cisplatin-induced kidney damage and provide potential strategies for AKI treatment.