Cytotoxic Effects and Oxidative Stress Produced by a Cyanobacterial Cylindrospermopsin Producer Extract versus a Cylindrospermopsin Non-Producing Extract on the Neuroblastoma SH-SY5Y Cell Line

Toxins (Basel). 2023 May 5;15(5):320. doi: 10.3390/toxins15050320.

Abstract

The incidence and interest of cyanobacteria are increasing nowadays because they are able to produce some toxic secondary metabolites known as cyanotoxins. Among them, the presence of cylindrospermopsin (CYN) is especially relevant, as it seems to cause damage at different levels in the organisms: the nervous system being the one most recently reported. Usually, the effects of the cyanotoxins are studied, but not those exerted by cyanobacterial biomass. The aim of the present study was to assess the cytotoxicity and oxidative stress generation of one cyanobacterial extract of R. raciborskii non-containing CYN (CYN-), and compare its effects with those exerted by a cyanobacterial extract of C. ovalisporum containing CYN (CYN+) in the human neuroblastoma SH-SY5Y cell line. Moreover, the analytical characterization of potential cyanotoxins and their metabolites that are present in both extracts of these cultures was also carried out using Ultrahigh Performance Liquid Chromatography-Mass Spectrometry, in tandem (UHPLC-MS/MS). The results show a reduction of cell viability concentration- and time-dependently after 24 and 48 h of exposure with CYN+ being five times more toxic than CYN-. Furthermore, the reactive oxygen species (ROS) increased with time (0-24 h) and CYN concentration (0-1.11 µg/mL). However, this rise was only obtained after the highest concentrations and times of exposure to CYN-, while this extract also caused a decrease in reduced glutathione (GSH) levels, which might be an indication of the compensation of the oxidative stress response. This study is the first one performed in vitro comparing the effects of CYN+ and CYN-, which highlights the importance of studying toxic features in their natural scenario.

Keywords: SH-SY5Y; cyanobacterial extracts; cylindrospermopsin; cytotoxicity; oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Toxins* / metabolism
  • Cell Line
  • Cyanobacteria Toxins
  • Cyanobacteria* / metabolism
  • Humans
  • Neuroblastoma*
  • Oxidative Stress
  • Tandem Mass Spectrometry
  • Uracil / metabolism
  • Uracil / toxicity

Substances

  • cylindrospermopsin
  • Bacterial Toxins
  • Cyanobacteria Toxins
  • Uracil

Grants and funding

This research was funded by the Spanish Ministerio de Economía y Competitividad (AGL2015-64558-R, MINECO/FEDER, UE) and the Spanish Ministerio de Ciencia e Innovación (PID2019-104890RBI00/AEI/10.13039/501100011033. A.Cascajosa-Lira thanks Ministerio de Universidades (FPU2019/01247). The authors thank the VII Plan Propio de Investigación y Transferencia—US 2022 (2022/00000298) for its financial support.