Biochemical responses of freshwater mussel Unio tumidus to titanium oxide nanoparticles, Bisphenol A, and their combination

  • Lesya Gnatyshyna
  • Halina Falfushynska
  • Oksana Horyn
  • Vira Khoma
  • Viktoria Martinyuk
  • Olena Mishchuk
  • Natalia Mishchuk
  • Oksana StoliarEmail author


Multiple interactions between different pollutants in the surface waters can cause unpredictable consequences. The aim of the study was to evaluate the combined effect of two widespread xenobiotics, titanium oxide nanoparticles (TiO2) and bisphenol A (BPA), on freshwater bivalve Unio tumidus. The specimens were exposed for 14 days to TiCl4 (Ti, 1.25 µM), TiO2 (1.25 μM), BPA (0.88 nM), or their combination (TiO2 + BPA). Every type of exposure resulted in a particular oxidative stress response: TiO2 had antioxidant effect, decreasing the generation of reactive oxygen species (ROS) and phenoloxidase (PhO) activity, and doubling reduced glutathione (GSH) concentration in the digestive gland; Ti caused oxidative changes by increasing levels of ROS, PhO and superoxide dismutase; BPA decreased the GSH level by a factor of two. In the co-exposure treatment, these indices as well as lysosomal membrane stability were not affected. All Ti-containing exposures caused elevated levels of metalated metallothionein (Zn,Cu-MT), its ratio to total metallothionein protein, and lactate/pyruvate ratio. Both BPA-containing exposures decreased caspase-3 activity. All exposures, and particularly co-exposure, up-regulated CYP450-dependent oxidation, lipid peroxidation and lipofuscin accumulation, lysosomal cathepsin D and its efflux, as well as alkali-labile phosphates in gonads and caused DNA instability (except for TiO2). To summarize, co-exposure to TiO2 + BPA produced an overlap of certain individual responses but strengthened the damage. Development of water purification technologies using TiO2 requires further studies of the biological effects of its mixtures. U. tumidus can serve as a sentinel organism in such studies.


Unio tumidus Combined exposure Metallothioneins Redox state Oxidative stress 



This work was funded by the grants from the Ministry of Education and Science of Ukraine for O. Stoliar (Projects M/4-2013; M/70-2017, 132B). We thank Dr. Sci. Olexandr Zaichenko and Dr. Sci. Natalia Mitina (Lviv Polytechnic National University, Ukraine) for their assistance with the physical–chemical characterization of the nanoparticles. The authors are grateful Dr. Inna Birchenko and for the scientific editing, linguistic and phraseological improvement of this manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Informed consent

All authors have approved this version of the work.

Supplementary material

10646_2019_2090_MOESM1_ESM.docx (118 kb)
Supplementary Information.


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Ternopil Volodymyr Hnatiuk National Pedagogical UniversityPyrohovaUkraine
  2. 2.I. Horbachevsky Ternopil State Medical UniversityTernopilUkraine
  3. 3.Rowan UniversityGlassboroUSA

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