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Specific nephrotoxicity and cardiotoxicity of BT-CAL®, Sigma Anti-bonding Molecule Calcium Carbonate, in mice
Ja-Young Jang1, Jingmei Cai, Jihyun Kim
1College of Veterinary Medicine, Chungbuk National University, Cheongju, Korea.
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.
Insights
Sigma Anti-bonding Molecule Calcium Carbonate (SAC) shows high anti-osteoporotic efficacy but causes significant toxicity. Repeated-dose studies in mice revealed dose-dependent decreases in body weight, organ damage, and high mortality, indicating safety concerns.
Area of Science:
- Pharmacology and Toxicology
- Biochemistry
- Materials Science
Background:
- Sigma Anti-bonding Molecule Calcium Carbonate (SAC) exhibits promising anti-osteoporotic properties.
- Its potential use as a pharmaceutical or functional food ingredient necessitates a thorough evaluation of its safety profile.
- Understanding the toxicological effects of repeated SAC administration is crucial for assessing its therapeutic feasibility.
Purpose of the Study:
- To investigate the repeated-dose toxicities of Sigma Anti-bonding Molecule Calcium Carbonate (SAC).
- To determine the feasibility of SAC as a drug or functional food ingredient based on its safety profile.
- To establish the no observed adverse effect level (NOAEL) for SAC in a preclinical model.
Main Methods:
- Male ICR mice were administered drinking water containing varying concentrations of SAC (0.006%, 0.02%, 0.06%) for four weeks.
- Body weight, feed and water consumption, organ weights, and serum biochemical parameters were monitored.
- Histopathological examinations of renal and cardiac tissues were performed to identify toxicological changes.
Main Results:
- SAC administration resulted in a dose-dependent decrease in body weight, feed, and water consumption.
- The high-dose group (0.06% SAC) experienced severe emaciation and a 70% mortality rate within three weeks.
- Significant increases in kidney and heart weights, along with elevated blood urea nitrogen, creatinine, AST, and CPK levels, indicated nephrotoxicity and cardiotoxicity.
- Microscopic analysis revealed renal crystal formation and cardiac fibrosis, suggesting mechanisms related to calcium overload and insoluble crystal deposition.
Conclusions:
- The no observed adverse effect level (NOAEL) of SAC in mice is below 0.006%.
- Repeated-dose administration of SAC leads to significant renal and cardiac toxicity.
- Long-term intake of SAC may pose serious risks to renal and cardiac functions, limiting its use as a drug or functional food ingredient.
