Acute hepatologic and nephrologic effects of calcitriol in Syrian golden hamster (Mesocricetus auratus)

Ewa Podgorska; Martyna Sniegocka; Marianna Mycinska; Wojciech Trybus; Ewa Trybus; Anna Kopacz-Bednarska; Olga Wiechec; Martyna Krzykawska-Serda; Martyna Elas; Teodora Krol; Krystyna Urbanska; Andrzej Slominski

doi:10.18388/abp.2018_2626

Ewa Podgorska Department of Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Poland
Martyna Sniegocka Department of Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Poland
Marianna Mycinska Department of Cell Biology and Electron Microscopy, Institute of Biology, The Jan Kochanowski University, Kielce, Poland
Wojciech Trybus Department of Cell Biology and Electron Microscopy, Institute of Biology, The Jan Kochanowski University, Kielce, Poland
Ewa Trybus Department of Cell Biology and Electron Microscopy, Institute of Biology, The Jan Kochanowski University, Kielce, Poland
Anna Kopacz-Bednarska Department of Cell Biology and Electron Microscopy, Institute of Biology, The Jan Kochanowski University, Kielce, Poland
Olga Wiechec Department of Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Poland
Martyna Krzykawska-Serda
Martyna Elas Department of Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Poland
Teodora Krol Department of Cell Biology and Electron Microscopy, Institute of Biology, The Jan Kochanowski University, Kielce, Poland
Krystyna Urbanska Department of Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Poland
Andrzej Slominski Department of Dermatology, Comprehensive Cancer Center, Cancer Chemoprevention Program, University of Alabama at Birmingham, Birmingham, AL, USA VA Medical Center, Birmingham, AL, USA

DOI: https://doi.org/10.18388/abp.2018_2626

Keywords: Calcitriol, Syrian golden hamster, hepatologic toxicity, nephrologic toxicity

Abstract

Although vitamin D is included in the group of fat-soluble vitamins, it must be considered as a prohormone. Its active forms including calcitriol have pleiotropic effects and play an important role in the regulation of cell proliferation, differentiation and apoptosis as well as in hormone secretion, and they show anti-cancer properties. Since calcitriol delivery can be beneficial for the organism, and Syrian golden hamsters represent a unique experimental model, we decided to investigate its toxicity in this species. In this study, we injected calcitriol intraperitoneally at doses 0 (control), 0.180±0.009 µg/kg and 0.717± 0.032 µg/kg. Animal behavior was observed for 72 hrs after injection, and afterwards blood and liver and kidney were collected for post-mortem examination, electron microscopy, and hematology analyses. The highest dose of calcitriol induced a change in animal behavior from calm to aggressive, and liver surface showed morphological signs of damage. Following the injection of calcitriol, ultrastructural changes were also observed in the liver and kidneys, e.g. vacuolization and increased number of mitochondria. There was also a trend for increased serum levels of aspartate aminotransferase (AST), but not of alanine aminotransferase (ALT) or GGTP (gamma-glutamyl transpeptidase). There was no change in Ca, Mg and P levels as well as in blood morphology between experimental and control groups. These results indicate that calcitriol at 0.717, but not at 0.18 µg/kg, may induce acute damage of the liver and kidneys, without inducing calcemia. We propose that the hepatotoxic effect of calcitriol in hamster constitutes the primary cause of behavioral changes.

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