Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | F1582-F1592 |
| Journal | American journal of physiology. Renal physiology |
| Volume | 317 |
| Issue number | 6 |
| DOIs | |
| State | Published - Dec 1 2019 |
Fingerprint
Keywords
- chronic kidney disease
- cisplatin
- fibrosis
- kidney repair
- nephrotoxicity
ASJC Scopus subject areas
- Physiology
- Urology
Cite this
Chronic effects of repeated low-dose cisplatin treatment in mouse kidneys and renal tubular cells. / Fu, Ying; Cai, Juan; Li, Fanghua; Liu, Zhiwen; Shu, Shaoqun; Wang, Ying; Liu, Yuxue; Tang, Chengyuan; Dong, Zheng.
In: American journal of physiology. Renal physiology, Vol. 317, No. 6, 01.12.2019, p. F1582-F1592.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Chronic effects of repeated low-dose cisplatin treatment in mouse kidneys and renal tubular cells
AU - Fu, Ying
AU - Cai, Juan
AU - Li, Fanghua
AU - Liu, Zhiwen
AU - Shu, Shaoqun
AU - Wang, Ying
AU - Liu, Yuxue
AU - Tang, Chengyuan
AU - Dong, Zheng
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
KW - chronic kidney disease
KW - cisplatin
KW - fibrosis
KW - kidney repair
KW - nephrotoxicity
UR - http://www.scopus.com/inward/record.url?scp=85076066150&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85076066150&partnerID=8YFLogxK
U2 - 10.1152/ajprenal.00385.2019
DO - 10.1152/ajprenal.00385.2019
M3 - Article
C2 - 31532246
AN - SCOPUS:85076066150
VL - 317
SP - F1582-F1592
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
SN - 0363-6135
IS - 6
ER -