Biodistribution of synthetic thymosin alpha1 in the serum, urine and major organs of mice.
Thymosin fraction 5 (TF5), a thymic preparation, has been shown to be an immune-potentiating agent consisting of biologically active polypeptide components with hormone-like activities. Thymosin alpha1 (T alpha1) was the first biologically active polypeptide to be purified from TF5 and completely characterized. It is an acidic peptide with an isoelectric point of 4.2 and a molecular weight of 3108. T alpha1 is considered a biological response modifier which amplifies T-cell immunity. In the present study, we have studied some pharmacokinetic properties of T alpha1 by measuring its concentrations in serum, urine and ten major organs of female Swiss-Webster mice following administration of 500 microg T alpha1 intraperitoneally. Using a modified enzymatic immunoassay, our data show a significant increase of T alpha1 in serum 2 min after injection and lasting for 2 h (average: 1.55 +/- 0.27 microg/ml). In urine, at four different time points after injection (20 min, 40 min, 2 h, 6 h), increased concentrations of T alpha1 were found between 24.2 and 25.4 microg/ml (average: 25 +/- 0.47 microg/ml). Of the 500 microg T alpha1 administered to mice, 8.97% was recovered at the end of the study, of which 2% corresponded to urine, 1.25% to serum (2 ml of serum per mouse), and 5.72% to organs. Since the urine/day volume and the serum volume of any Swiss Webster mouse is ca 2 ml, additional extrapolation of the above mentioned values could show percentages of recovery close to 40% for urine and 2.5% for serum. In most of the organs, the wet weight concentrations of T alpha1 increased significantly during the first 40 min after injection in comparison to their baseline wet weight concentrations. These organs consisted of the following: thymus (33.1 +/- 3.5 microg/g vs 18 microg/g baseline); lungs (7.7 +/- 1.1 microg/g vs 1.9 microg/g baseline); spleen (15.6 +/- 0.7 microg/g vs 5.6 microg/g); kidneys (6.2 +/- 1.1 microg/g vs 3.9 microg/g); ovaries (9.2 +/- 1.4 microg/g vs 0 microg/g); and peritoneal fat (4 +/- 1 microg/g vs 0 microg/g). No significant increases were observed in the liver (1.7 +/- 0.1 microg/g vs 1.4 microg/g) and heart (0.7 +/- 0.5 microg/g vs 0 microg/g). Increased concentrations of T alpha1 were not detected in the brain and skeletal muscle tissues. These pharmacokinetic studies of T alpha1 in mice indicate that rapid renal excretion of T alpha1 represents a major source of humoral loss following I.P. administration. Recent preliminary studies in humans confirm that the kidney rapidly releases high levels of T alpha1 in urine in a time frame consistent with that observed in mice.
Badamchian
M
M
Department of Biochemistry and Molecular Biology, The George Washington University School of Health Sciences, Washington, DC 20037, U.S.A.
Mora
C A
CA
Baumann
C A
CA
Paino
J E
JE
Goldstein
A L
AL
D000273:Adipose Tissue / Q000378:metabolism; D000276:Adjuvants, Immunologic / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D000818:Animals; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007668:Kidney / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D051379:Mice; D010053:Ovary / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D000077596:Thymalfasin; D013947:Thymosin / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D013950:Thymus Gland / Q000378:metabolism; D014018:Tissue Distribution
D000276:Adjuvants, Immunologic; D013947:Thymosin; D000077596:Thymalfasin