Lab Anim Res.  2013 Mar;29(1):7-11. 10.5625/lar.2013.29.1.7.

Specific nephrotoxicity and cardiotoxicity of BT-CAL(R), Sigma Anti-bonding Molecule Calcium Carbonate, in mice

• Jang JY
• Cai J
• Kim J
• Kyung J
• Kim D
• Choi EK
• Kim Y
• Kim KS
• Park D
• Kang HG
• Kim YB

• KMID: 2312097
• DOI: http://doi.org/10.5625/lar.2013.29.1.7

Abstract

According to a high anti-osteoporotic efficacy of Sigma Anti-bonding Molecule Calcium Carbonate (SAC), repeated-dose toxicities of SAC were investigated to assess its feasibility as drug or functional food ingredient. Male ICR mice were given drinking water containing 0.006, 0.02 or 0.06% SAC for 4 weeks. SAC feeding decreased the body weights and feed and water consumptions of mice in a dose-dependent manner, especially, leading to severe emaciation and 70% death in 3 weeks in the high-dose (0.06%) group. Not only kidney and heart weights, but also the levels of blood urea nitrogen, creatinine, aspartate transaminase, and creatine phospokinase significantly increased after SAC administration, indicative of nephrotoxicity and cardiotoxicity. Such renal and cardiac toxicities were also confirmed by microscopic findings, exhibiting renal crystals and cardiac fibrosis, which may be due to the insoluble crystal formation and calcium overload, respectively. In conclusion, it is suggested that no observed adverse effect level of SAC is lower than 0.006% in mice, and that a long-term intake may cause serious adverse effects on renal and cardiac functions.

Keyword

BT-CAL(R); Sigma Anti-bonding Molecule Calcium Carbonate; nephrotoxicity; cardiotoxicity

MeSH Terms

Animals
Aspartate Aminotransferases
Blood Urea Nitrogen
Body Weight
Calcium
Calcium Carbonate
Creatine
Creatinine
Drinking Water
Emaciation
Fibrosis
Functional Food
Heart
Humans
Kidney
Male
Mice
Mice, Inbred ICR
No-Observed-Adverse-Effect Level
Weights and Measures
Aspartate Aminotransferases
Calcium
Calcium Carbonate
Creatine
Creatinine
Drinking Water

Figure

• 

  Figure 1 Change in body weights (A) and daily feed (B) and water (C) consumptions during feeding Sigma Anti-bonding Molecule Calcium Carbonate (SAC). •, water alone; ▾, 0.006% SAC; ▪, 0.02% SAC; ♦, 0.06% SAC.

• 

  Figure 2 Representative findings of the kidneys. Note the brown crystals (arrows) in the renal tubules filled with eosinophilic contents in a mouse fed Sigma Anti-bonding Molecule Calcium Carbonate (0.02%) (B), compared with the normal features in a normal animal (A). Hematoxylin-eosin staining.

• 

  Figure 3 Representative findings of the hearts. Note the fibrosis (stained blue) in the cardiac muscles in a mouse fed Sigma Antibonding Molecule Calcium Carbonate (0.02%) (B), compared with the normal features in a normal animal (A). Masson's trichrome staining.

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