1. Academic Validation
  2. Evaluation of the safety and tolerability of tamoxifen for ischemia-incited renal injury in mice

Evaluation of the safety and tolerability of tamoxifen for ischemia-incited renal injury in mice

  • Am J Transl Res. 2018 Jul 15;10(7):2184-2194.
Yuxi Wang 1 Zhi Zhao 1 Weiqi Yang 1 Lin Li 2 Fengming Zhu 1 Guangchang Pei 1 Juan Yang 1 Han Zhu 1 Huzi Xu 1 Meng Wang 1 Qian Yang 1 Zhizhi Hu 1 Pengge Wang 1 Gang Xu 1 Rui Zeng 1 Ying Yao 1
Affiliations

Affiliations

  • 1 Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology 1095 Jiefang Ave, Wuhan 430030, Hubei, China.
  • 2 Department of Laboratory Medicine, Taihe Hospital, Hubei University of Medicine Shiyan 442000, Hubei, China.
PMID: 30093955
Abstract

Tamoxifen is used to activate tamoxifen-dependent Cre recombinase (CreER) to generate time- and tissue-specific genetically mutant mice. However, tamoxifen is also an active estrogen analogue that binds with higher affinity to estrogen receptors and exhibits anti-apoptosis, anti-inflammation, and antifibrotic properties. Renal ischemia reperfusion (I/R) injury is characterized by increased Apoptosis and inflammation, so optimal utility of tamoxifen-inducible CreER genetic systems in I/R model is important. The purpose of this study was to optimize the tamoxifen dose and evaluate its safety and tolerability in the development of mouse I/R injury. Seven-week-old C57/B6 mice were subjected to moderate reversible unilateral I/R and then injected intraperitoneally daily for 5 days with tamoxifen at doses of 50, 100, or 200 mg/kg/day. Regardless of the time of sacrifice, at 5 day or 28 day after I/R injury, there were no differences in pathological damage, Apoptosis, inflammation, or the extent of fibrosis between untreated and treated mice from the time point of acute kidney injury (AKI) to subsequently chronic kidney disease. Data above indicated that tamoxifen with a dose among 0 to 200 mg/kg/day was safe and tolerable for mice, without influencing I/R induced kidney injury in mice. The results suggest that tamoxifen-inducible CreER genetic systems can be safely used in the mouse I/R model.

Keywords

Inflammation; acute kidney injury; interstitial fibrosis; ischemia reperfusion injury; tamoxifen.

Figures
Products