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Hepatotoxicity and nephrotoxicity of 3-bromopyruvate in mice
Qiong Pan1, Yiming Sun2, Qili Jin3
1Graduate student, Department of Pharmacy, China. Technical procedures, manuscript preparation.
Purpose::
To investigate the hepatotoxicity and nephrotoxicity of 3-Bromopyruvate (3BP) in mice.
Methods::
Fifteen nude mice were grafted subcutaneously in the left flank with MDA-MB-231 cells, then all mice were divided into control group (PBS), 3BP group (8 mg/kg), positive group (DNR: 0.8 mg/kg) when tumor volume reached approximately 100 mm3. 28 days later, tumors, livers and kidneys were stored in 4 % formalin solution and stained with hematoxylin and eosin staining. The Kunming mice experiment included control group (PBS), 3BP group (4mg/kg; 8mg/kg; 16mg/kg), positive group (DNR: 0.8 mg/kg). 24 hours later, the blood were used for the determination of hepatic damage serum biomarkers. Livers were stored in 4 % formalin solution for the later detection.
Results::
3BP at the dose of 8mg/kg had a good effect on inhibiting tumor growth in nude mice and did not damage liver and kidney tissues. Kunming mice experiment showed 3BP at the dose of 16mg/kg did damage to liver tissues.
Conclusion::
3-Bromopyruvate at the dose of suppressing tumor growth did not exhibit hepatotoxicity and nephrotoxicity in nude mice, and the effect on liver was confirmed in Kunming mice.
Insights
3-Bromopyruvate (3BP) at doses used for tumor suppression showed no liver or kidney toxicity in mice. Higher doses in Kunming mice indicated potential liver damage, warranting further investigation.
Area of Science:
- Oncology
- Toxicology
- Pharmacology
Background:
- 3-Bromopyruvate (3BP) is investigated for its anti-cancer properties.
- Understanding the toxicological profile of 3BP is crucial for its therapeutic development.
Purpose of the Study:
- To evaluate the potential hepatotoxicity and nephrotoxicity of 3-Bromopyruvate (3BP) in mouse models.
- To assess the safety of 3BP at doses effective for tumor growth inhibition.
Main Methods:
- Nude mice bearing MDA-MB-231 tumors received 3BP (8 mg/kg) or control (PBS).
- Kunming mice were administered varying doses of 3BP (4, 8, 16 mg/kg) or control.
- Histopathological examination of liver and kidney tissues and serum biomarker analysis were performed.
Main Results:
- 3BP at 8 mg/kg demonstrated tumor growth inhibition without causing observable liver or kidney damage in nude mice.
- In Kunming mice, 3BP at a dose of 16 mg/kg resulted in discernible liver tissue damage.
Conclusions:
- 3-Bromopyruvate (3BP) at tumor-suppressing doses appears safe regarding hepatotoxicity and nephrotoxicity in mice.
- Higher concentrations of 3BP may induce liver toxicity, necessitating careful dose selection in therapeutic applications.
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