Combination of zinc and selenium alleviates ochratoxin A-induced fibrosis via blocking ROS-dependent autophagy in HK-2 cells

• Published in: Journal of trace elements in medicine and biology 2022-01, Vol.69, p.126881, Article 126881
• Main Authors: Le, Guannan, Yang, Lulu, Du, Heng, Hou, Lili, Ge, Lei, Sylia, Ardache, Muhmood, Azhar, Chen, Xinxiang, Han, Bo, Huang, Kehe
• Format: Article
• Language: English
• Subjects: Antioxidants; Autophagy; Fibrosis; Humans; Hydrogen Peroxide; Ochratoxin A; Ochratoxins; Reactive Oxygen Species; Renal fibrosis; ROS; Selenium - pharmacology; Selenomethionine; Selenomethionine - pharmacology; Zinc; Zinc - pharmacology
• ISSN: 0946-672X; 1878-3252
• DOI: 10.1016/j.jtemb.2021.126881

[Display omitted] •OTA induced cytotoxicity and increased fibrosis factors expression in HK-2 cells.•Zinc and SeMet alone or in combination alleviated OTA-induced cytotoxicity and fibrosis in HK-2 cells.•Protective effects of zinc and SeMet combined application were better than its alone.•Zinc and SeMet alleviated OTA-induced fibrosis via blocking ROS-dependent autophagy signaling pathway. Ochratoxin A (OTA) is a mycotoxin produced by Aspergillus and Penicillium. The key target organ of OTA toxicity is the kidney, which has a significant impact on human health. Recently, nutrition regulation is suggested to be an effective protection against mycotoxins contamination. The current study investigated the combined protective effects of zinc and selenomethionine (SeMet) (a major component of organic selenium) on OTA-induced renal fibrosis and their potential mechanisms in human renal proximal tubule epithelial cells (HK-2 cells). Cytotoxicity of different concentrations of OTA, zinc and SeMet on HK-2 cells was detected by cell viability, lactate dehydrogenase (LDH) and apoptotic nuclei assays. The expression of fibrosis biomarkers was detected by Real-Time PCR, western blotting and indirect immunofluorescence assays. The production of reactive oxygen species (ROS) was detected by ROS assay kit. The protein expression of autophagy biomarkers was detected by western blotting assay. Cytotoxicity was induced by OTA treatment in a dose-dependent manner, and it was attenuated by zinc or SeMet application in HK-2 cells. Zinc or SeMet application also down-regulated the expression of fibrosis biomarkers, and the combination of them displayed better effects. In addition, OTA increased intracellular ROS level and activated autophagy in a dose-dependent manner, and it was reversed by zinc and SeMet combined application. With the treatment of hydrogen peroxide (H2O2) or rapamycin (the specific activator of autophagy), the combined protective effects of zinc and SeMet were abolished. Zinc and SeMet application alleviated OTA-induced cytotoxicity and fibrosis in HK-2 cells. Combination of them was more effective than its individual application. The present study manifest novel insight about the alleviation of OTA-induced nephrotoxicity by nutrition regulation, and had a guiding effect on the clinical supplementation of nutritional elements.