[논문]Characterization of Toxicological Properties of L-Lysine Polymers in CD-1 Mice

Titlow, William B.; Lee, Chul-Hoon; Ryou, Chongsuk

doi:10.4014/jmb.1302.02055

Characterization of Toxicological Properties of L-Lysine Polymers in CD-1 Mice 원문보기

Journal of microbiology and biotechnology, v.23 no.7, 2013년, pp.1015 - 1022

Titlow, William B. (Department of Microbiology, Immunology, and Molecular Genetics, College of Medicine, University of Kentucky) , Lee, Chul-Hoon (Department of Pharmacy, College of Pharmacy, Hanyang University) , Ryou, Chongsuk (Department of Pharmacy, College of Pharmacy, Hanyang University)

Abstract ▼ AI-Helper

We recently showed that polylysine, the polymer of lysines, retains anti-prion activity. Although the effectiveness of prion inhibition by polylysine was demonstrated with the regimen tolerated in mice, a determination of quantitative polylysine toxicity is necessary to precisely address the in vivo toxicity level of polylysine. In this communication, we report the results of body weight monitoring and hematologic tests performed in CD-1 mice that received two different tolerable dosages of polylysine for an either 5-day or 4-week period. We found that there was no significant alteration in overall serum chemistry, blood cell count, and body weight gain compared with controls. The only notable quantitative change with statistical significance was the decrease of platelet numbers in mice subchronically administered with polylysine. Our results suggest that polylysine is harmless in mice if administered for a short period, but administrations of polylysine in mice may require considerate attention for safety in future investigations as mice chronically receive tolerable doses of polylysine.

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A consistent and uninterrupted lightdark cycle (14 h lights on/10 h lights off cycle) was maintained for he lighting condition. After a week in the animal facility, the now 5-week-old mice were randomly grouped and subjected to polylysine administration.
The blood cell count was performed using a Heska CBC-Diff Veterinary Hematology System (Heska, USA). The serum chemistry test was conducted using a Hemagen Analyst chemistry analyzer system with a VET 16 Panels + rotor (Hemagen Diagnostics Inc., USA).

대상 데이터

At the time of euthanasia, sera and whole blood were immediately collected from the left ventricle of the heart using methods described elsewhere [4]. EDTA-treated blood (0.5 ml) for blood cell count and 0.2 ml of serum for chemical analysis were sent to The Division of Laboratory and Animal Resources at the University of Kentucky. The blood cell count was performed using a Heska CBC-Diff Veterinary Hematology System (Heska, USA).
Thus, it is possible that the same CD-1 strain bred in the facility of different suppliers could be not completely identical. The CD1 mice used in this study were from Harlan Laboratories Inc., whereas the reference data were based on CD-1 mice from Charles Rivers.
The mice were kept in a standard “shoebox” cage with irradiated bedding (7090A Teklad Aspen Sani Chips, Harlan Laboratories Inc.).

이론/모형

The differences between the test and control groups were compared using the one-way analysis of variance method.

성능/효과

In conclusion, no differences in survival, weight gain, and the values of toxicity parameters in blood system integrity and serum chemistry suggest that the polylysine treatments described in this study did not contribute to toxicity in mice. However, the decrease of platelet numbers upon subchronic polylysine administration suggests a potential risk of polylysine treatments for extended periods.
However, this observation was not consistently witnessed in mice that were given polylysine for an extended period (Table 4). In subchronic tests, although the changes in some parameters, such as aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, phosphorous, albumin, cholesterol, and creatinine kinase, were statistically significant (p = 0.001-0.03), altered values were near or within the normal ranges (Table 4). These data indicate that polylysine administration for a subchronic period does not induce toxic biochemical events and, thus, is tolerable in mice.

참고문헌 (25)

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Characterization of Toxicological Properties of L-Lysine Polymers in CD-1 Mice 원문보기

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Characterization of Toxicological Properties of L-Lysine Polymers in CD-1 Mice 원문보기

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