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Repeated-dose toxicity of HSP27-binding heptapeptide in mice
1Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
Abstract:
Heptapeptide, including seven amino acids of the PKC delta V5 region, which can bind HSP27 and abrogate HSP27-mediated resistance against IR and cisplatin ( Kim et al., 2007 ), was examined for single- and repeated-dose toxicity in mice. The single-dose experiment was performed with an intravenous and intraperitoneal injection of 100 mg/kg of heptapeptide, and the repeated-dose experiment was 14 doses over 28 days at 0, 5, 25, and 100 mg/kg of heptapeptide. Observations included clinical signs, mortality, body and organ weights, hematology, and serum biochemistry. No effects of heptapeptide on detected parameters were observed, and these findings indicated heptapeptide may be a possible therapeutic candidate without significant toxicity.
Insights
This study investigated the safety of a novel heptapeptide. The heptapeptide demonstrated no significant toxicity in mice, suggesting its potential as a therapeutic agent.
Area of Science:
- Biochemistry
- Pharmacology
- Toxicology
Background:
- Heptapeptide, derived from the PKC delta V5 region, binds HSP27.
- This binding can overcome HSP27-mediated resistance to IR and cisplatin.
- Understanding the safety profile of this heptapeptide is crucial for therapeutic development.
Purpose of the Study:
- To evaluate the single- and repeated-dose toxicity of the heptapeptide in a mouse model.
- To identify any adverse effects associated with heptapeptide administration.
Main Methods:
- Single-dose toxicity: Intravenous and intraperitoneal injection of 100 mg/kg heptapeptide.
- Repeated-dose toxicity: 14 doses over 28 days at 0, 5, 25, and 100 mg/kg.
- Comprehensive monitoring: Clinical signs, mortality, body/organ weights, hematology, and serum biochemistry.
Main Results:
- No observed adverse effects across all measured parameters in both single- and repeated-dose studies.
- Heptapeptide administration did not induce significant changes in clinical signs, mortality, or physiological markers.
Conclusions:
- The examined heptapeptide exhibits a favorable safety profile in mice.
- These findings support the potential of heptapeptide as a therapeutic candidate with low toxicity.
