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

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 demonstrate 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, liver and kidneys 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 the liver surface showed morphological signs of damage. Following 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 0.180 µg/kg, may induce acute damage to the liver and kidneys, without inducing calcemia. We propose that the hepatotoxic effect of calcitriol in hamster constitutes the primary cause of behavioral changes.

Vitamin D and its low calcemic analogs modulate the anticancer properties of cisplatin and dacarbazine in the human melanoma A375 cell line

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Case Report: A Case Series Linked to Vitamin D Excess in Pet Food: Cholecalciferol (Vitamin D3) Toxicity Observed in Five Cats

“…From a histological perspective, acute vitamin D toxicity could also be related to liver and kidney damage resulting from 1,25(OH)2D3-induced distress on hepatocytes and the activation of defense mechanisms on kidney cells, as observed recently in hamsters being tested with a high dose of 1,25(OH)2D3 ( 56 ).…”

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Effect of Hypervitaminosis D3 on Liver, Kidney Functions in White Rats

“…It is worth noting that the study of Podgorska et al (2018) indicate that Liver toxicity characterized by biochemical parameters, there was only a slight increase in the alanine aminotransferase (ALT) after calcitriol treatment, which was statistically insigni icant and increased in the aspartate aminotransferase (AST) values as compared with the untreated control. In addition to the tested doses, 50 nM and 200 nM of calcitriol (vitamin D 3 ) may lead to acute effects on the liver and kidneys.…”