Mechanism for inhibition of cytotoxicity of Shiga toxin by luteolin

• Published in: Toxicology in vitro Vol. 87; p. 105537
• Main Authors: Yuan, Lu, Nakamichi, Rinako, Hirata, Yuka, Matsuda, Ayaka, Shinohara, Yui, Yamada, Akifumi, Masuda, Yoshimitsu, Honjoh, Ken-ichi, Miyamoto, Takahisa
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.03.2023
• Subjects: Animals; Cell-free protein synthesis; Chlorocebus aethiops; Cytotoxicity; Depurination; Enterohemorrhagic Escherichia coli; Luteolin; Luteolin - pharmacology; RNA, Ribosomal, 28S; Shiga toxin; Shiga Toxin - toxicity; Shiga Toxin 1 - metabolism; Shiga Toxin 1 - toxicity; Shiga Toxin 2 - metabolism; Shiga Toxin 2 - toxicity; Stilbene; Vero Cells; Shiga toxin; Cell-free protein synthesis; Cytotoxicity; Enterohemorrhagic Escherichia coli; Luteolin; Depurination; Stilbene
• ISSN: 0887-2333; 1879-3177
• DOI: 10.1016/j.tiv.2022.105537

Enterohemorrhagic or Shiga toxin-producing Escherichia coli is a food-poisoning bacterium that grows in the intestine to produce Shiga toxin (Stx). In this study, the effects of 20 polyphenols on the cytotoxicity of Stx1 and Stx2 in Vero cells were investigated. Among these, epigallocatechin gallate, butein, isorhapontigenin, hesperetin, morin, luteolin, resveratrol, and rhapontigenin showed inhibitory effects on the cytotoxicity of Stxs at 0.4 mmol/L. Furthermore, Vero cells pre-treated with these polyphenols were resistant to Stx at 0.4 mmol/L. However, luteolin showed the most potent inhibitory and cytoprotective effect against Stxs at 0.08 mmol/L or more. This inhibitory mechanism of luteolin was determined using a cell-free protein synthesis system and quantitative reverse transcription PCR assay to detect depurination of 28S rRNA in Vero cells. Luteolin did not inhibit the cell-free protein synthesis by Stxs, suggesting that the enzymatic activity of the Stx A subunit was not inhibited by luteolin. The depurination of 28S rRNA by Stxs was also investigated in Vero cells. The 28S rRNA depurination by Stxs was suppressed in Vero cells treated with Stxs which had been pretreated with luteolin. These results suggest that luteolin inhibits the incorporation of Stxs into Vero cells. This is the first report to show that luteolin inhibits the cytotoxicity of both Stx1 and Stx2 by inhibiting the incorporation of Stxs into Vero cells. •Luteolin inhibited cytotoxicity of Stxs and protected Vero cells from the toxins.•Luteolin did not suppress the inhibition of cell-free protein synthesis by Stxs.•Stxs pretreated with luteolin suppressed the depurination of 28S rRNA by Stxs in Vero cells.•Luteolin seems to inhibit incorporation of Stxs into Vero cells.