Chronic effects of repeated low-dose cisplatin treatment in mouse kidneys and renal tubular cells

• Published in: American journal of physiology. Renal physiology Vol. 317; no. 6; pp. F1582 - F1592
• Main Authors: Fu, Ying, Cai, Juan, Li, Fanghua, Liu, Zhiwen, Shu, Shaoqun, Wang, Ying, Liu, Yuxue, Tang, Chengyuan, Dong, Zheng
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.12.2019
• Subjects: Animal models; Animals; Antineoplastic Agents - toxicity; Apoptosis; Apoptosis - drug effects; Cell culture; Cells, Cultured; Chemotherapy; Chronic effects; Cisplatin; Cisplatin - toxicity; Cytokines; Fibrosis; Glomerular Filtration Rate; Inflammation; Kidney - drug effects; Kidney - pathology; Kidney diseases; Kidney Function Tests; Kidney Glomerulus - pathology; Kidney Tubules - drug effects; Kidney Tubules - pathology; Male; Mice; Mice, Inbred C57BL; Organ Size; Renal cell carcinoma; Renal function; Renal Insufficiency, Chronic - chemically induced; Renal Insufficiency, Chronic - pathology; chronic kidney disease; fibrosis; nephrotoxicity; cisplatin; kidney repair
• ISSN: 1931-857X; 1522-1466
• DOI: 10.1152/ajprenal.00385.2019

Cisplatin is a commonly used chemotherapeutic drug for cancer treatment, but its nephrotoxicity may lead to the deterioration of renal function. Previous work has been focused on cisplatin-induced acute kidney disease, whereas the mechanism of chronic kidney disease after cisplatin chemotherapy is largely unknown. In the present study, we have characterized the mouse model of chronic kidney defects induced by repeated low-dose cisplatin treatment. We have also established a relevant cell culture model. In the animal model, C57 mice were given weekly injection of 8 mg/kg cisplatin for 4 wk. This led to a sustained decline of kidney function. These mice showed loss of kidney mass, interstitial fibrosis, continued activation of inflammatory cytokines, and appearance of atubular glomeruli. In the cell model, the BUMPT mouse proximal tubular cell line was treated four times with 1-2 μM cisplatin, resulting in low levels of apoptosis and the expression of fibrosis proteins and profibrotic factors. These data suggest that repeated treatment with low-dose cisplatin causes long-term renal pathologies with characteristics of chronic kidney disease.