NDLI: Effects of Spermine-Conjugated Bowman-Birk Inhibitor (Spermine-BBI) on Carcinogenesis and Cholesterol Biosynthesis in Mice

Content Provider	Springer Nature Link
Author	Kennedy, Ann R. Kritchevsky, David Shen, Wei Chiang
Copyright Year	2003
Abstract	Purpose. The goals of the studies reported here were to evaluate the effects of the soybean-derived protease inhibitor known as the Bowman-Birk inhibitor (BBI) and its spermine-conjugate (spermine-BBI) on the prevention of lung tumorigenesis and the reduction of heart disease parameters. Methods. Both spermine-BBI and purified BBI (pBBI), at a dose of 20 mg/kg body weight, were administered as intraperitoneal injections to animals treated with the chemical carcinogen 3-methylcholanthrene (MCA) to determine their effects on chemically induced lung tumorigenesis in A/J mice. In addition, the effects of spermine-BBI and pBBI on the aortic cholesterol content and the percent ester in the mice were determined. Results. The characteristics of the animals in the various treatment groups were comparable in terms of behavioral phenomena, weight gain, and lack of deaths during the experimental period. Thus, there was no detectable toxicity in spermine-BBI-treated mice. Both spermine-BBI and pBBI had a significant suppressive effect on MCA-induced lung tumors, with spermine-BBI being more effective than pBBI. Spermine-BBI was considerably more effective than pBBI at affecting heart-disease-related parameters. The amount of esterified cholesterol present in the aortas of mice treated with spermine-BBI was 9% lower than that of the controls. Both pBBI and spermine-BBI reduced total cholesterol levels in the blood, with pBBI reducing the cholesterol level by 15.5% and spermine-BBI by 33.3%. Conclusions. Spermine-BBI can prevent lung carcinogenesis without detectable toxic effects; therefore, it is concluded that lung targeting by the cationization of polypeptides can be achieved without apparent toxicity. The increase in retention of spermine-BBI compared to pBBI in liver tissue may make a difference for the heart disease parameters evaluated. Although spermine-BBI is capable of reducing the total cholesterol and ester levels in mice, pBBI did not have as great an effect on these parameters. Because the liver is the major site for the production of cholesterol, the localization of spermine-BBI in liver tissue may account for the greater effect of spermine-BBI on blood cholesterol levels. Spermine-BBI was administered to animals for only the first 2 months of the 4-month assay period before animal sacrifice, so the results suggest that the effects of spermine-BBI on the parameters related to heart disease are long-lasting, as are the effects of both pBBI and spermine-BBI on lung tumorigenesis.
Starting Page	1908
Ending Page	1910
Page Count	3
File Format	PDF
ISSN	07248741
Journal	Pharmaceutical Research
Volume Number	20
Issue Number	12
e-ISSN	1573904X
Language	English
Publisher	Kluwer Academic Publishers-Plenum Publishers
Publisher Date	2003-01-01
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Pharmacology/Toxicology Pharmacy Biochemistry Medical Law Biomedical Engineering
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science

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