Molecular insights of copper sulfate exposure-induced nephrotoxicity: Involvement of oxidative and endoplasmic reticulum stress pathways

Chongshan Dai, Qiangqiang Liu, Daowen Li, Gaurav Sharma, Jianli Xiong, Xilong Xiao

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

The precise pathogenic mechanism in Cu exposure-cause nephrotoxicity remains unclear. This study investigated the underlying molecular mechanism of copper sulfate (CuSO4)-induced nephrotoxicity. Mice were treated with CuSO4 at 50, 100, 200 mg/kg/day or co-treated with CuSO4 (200 mg/kg/day) and 4-phenylbutyric acid (4-PBA, 100 mg/kg/day) for 28 consecutive days. HEK293 cells were treated with CuSO4 (400 µM) with or without superoxide dismutase, catalase or 4-PBA for 24 h. Results showed that CuSO4 exposure can cause renal dysfunction and tubular necrosis in the kidney tissues of mice. CuSO4 exposure up-regulated the activities and mRNA expression of caspases-9 and-3 as well as the expression of glucose-regulated protein 78 (GRP78), GRP94, DNA damage-inducible gene 153 (GADD153/CHOP), caspase-12 mRNAs in the kidney tissues. Furthermore, superoxide dismutase and catalase pre-treatments partly inhibited CuSO4-induced cytotoxicity by decreasing reactive oxygen species (ROS) production, activities of caspases-9 and-3 and DNA fragmentations in HEK293 cells. 4-PBA co-treatment significantly improved CuSO4-induced cytotoxicity in HEK293 cells and inhibited CuSO4 exposure-induced renal dysfunction and pathology damage in the kidney tissues. In conclusion, our results reveal that oxidative stress and endoplasmic reticulum stress contribute to CuSO4-induced nephrotoxicity. Our study highlights that targeting endoplasmic reticulum and oxidative stress may offer an approach for Cu overload-caused nephrotoxicity.

Original languageEnglish (US)
Article number1010
Pages (from-to)1-15
Number of pages15
JournalBiomolecules
Volume10
Issue number7
DOIs
StatePublished - Jul 2020

Keywords

  • Apoptosis
  • Copper
  • Cytotoxicity
  • Endoplasmic reticulum stress
  • Kidney
  • Oxidative stress

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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