Moderate aging does not exacerbate cisplatin-induced kidney injury or fibrosis despite altered inflammatory cytokine expression and immune cell infiltration

尽管炎症细胞因子表达和免疫细胞浸润发生改变,但中度衰老不会加剧顺铂引起的肾损伤或纤维化

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作者:Cierra N Sharp, Mark Doll, Tess V Dupre, Levi J Beverly, Leah J Siskind

Abstract

Aging is a risk factor for certain forms of kidney injury due to normal physiological changes, but the role of aging in cisplatin-induced kidney injury is not well defined in humans or animal models of the disease. To improve on current knowledge in this field, we treated 8- and 40-wk-old FVB/n mice with one high dose of cisplatin as a model of acute kidney injury or with repeated low doses of cisplatin (7 mg/kg cisplatin once a week for 4 wk) as a clinically relevant model of chronic kidney disease to determine if aging exacerbates cisplatin-induced kidney injury. Levels of acute kidney injury were comparable in 8- and 40-wk-old mice. In 40-wk-old mice, fibrotic markers were elevated basally, but treatment with cisplatin did not exacerbate fibrosis. We concluded that this may be the result of a decreased inflammatory response in 40-wk-old cisplatin-treated mice compared with 8-wk-old mice. Despite a decreased inflammatory response, the level of immune cell infiltration was greater in 40-wk-old cisplatin-treated mice than 8-wk-old mice. Our data highlight the importance of examining age as a risk factor for cisplatin-induced kidney injury.

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