Protective Effect of alpha-Tocopherol Against Ochratoxin A in Kidney Cell Line HK-2

J Food Prot. 2023 May;86(5):100082. doi: 10.1016/j.jfp.2023.100082. Epub 2023 Mar 28.

Abstract

Food safety is a top priority for the protection of infants and young children. Ochratoxin A (OTA) is an emerging concern due to its high toxicity and occurrence in a wide range of agricultural crops and their derived food products including those foods and snacks destined for infants and young children. OTA is considered as a possible human carcinogen, and its main target organ is the kidney. The objective of this study was to investigate the protective effect of α-tocopherol against oxidative stress induced by OTA using human proximal tubule epithelial cells (HK-2). OTA showed dose-dependent increase in cytotoxicity (IC50 = 161 nM, p < 0.05) at 48 h, while treatment up to 2 mM α-tocopherol did not change cell viability. Levels of the reduced form of glutathione (GSH) were decreased with α-tocopherol treatment, although the ratio of the oxidative form (GSSG) to GSH remained the same. Among several genes associated with oxidative stress, expression of superoxide dismutase 1 (SOD1), catalase (CAT), glutathione reductase (GSR), and kidney injury molecule-1 (KIM-1) were significantly up-regulated by OTA treatment. CAT and GSR showed decreased expression at 0.5-2 mM α-tocopherol and OTA at IC50 value, KIM-1 was decreased at 0.5 mM α-tocopherol and OTA at IC50 value, and nuclear factor erythroid 2-related factor 2 (Nrf2) was decreased at 0.5-1 mM α-tocopherol and OTA at IC50 value. In addition, the levels of malondialdehyde (MDA) were increased significantly by OTA while significantly decreased by α-tocopherol. The results show that α-tocopherol may alleviate potential OTA-induced renal damage and oxidative stress through reducing cytotoxicity and enhancing the antioxidant defense systems.

Keywords: HK-2; Kidney; Ochratoxin A (OTA); Oxidative Stress; Protective Effect; α-Tocopherol.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cell Line
  • Child
  • Child, Preschool
  • Epithelial Cells / metabolism
  • Glutathione / metabolism
  • Glutathione / pharmacology
  • Humans
  • Kidney / metabolism
  • Ochratoxins* / toxicity
  • Oxidative Stress
  • alpha-Tocopherol* / metabolism
  • alpha-Tocopherol* / pharmacology

Substances

  • ochratoxin A
  • alpha-Tocopherol
  • Ochratoxins
  • Glutathione