Biodistribution of synthetic thymosin α1 in the serum, urine and major organs of mice

Abstract

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 α 1 ( Tα 1) 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. Tα 1 is considered a biological response modifier which amplifies T-cell immunity. In the present study, we have studied some pharmacokinetic properties of Tα 1 by measuring its concentrations in serum, urine and ten major organs of female Swiss-Webster mice following administration of 500 μg Tα 1 intraperitoneally. Using a modified enzymatic immunoassay, our data show a significant increase of Tα 1 in serum 2min after injection and lasting for 2 h (average: 1.55 ± 0.27 μg/ml). In urine, at four different time points after injection (20min, 40 min, 2h, 6 h), increased concentrations of Tα 1 were found between 24.2 and 25.4μg/ml (average: 25 ± 0.47 μg/ml). Of the 500μg Tα 1 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 Tα 1 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 μ/g vs 18 μ/g baseline); lungs (7.7±1.1 μg/g vs 1.9 μg/g baseline); spleen (15.6±0.7 μg/g vs 5.6 μg/g); kidneys (6.2±1.1 μg/g vs 3.9 μg/g); ovaries (9.2±1.4 μg/g vs 0 μg/g); and peritoneal fat (4±1 μg/g vs 0 μg/g). No significant increases were observed in the liver (1.7±0.1 μg/g vs 1.4 μg/g) and heart (0.7±0.5 μg/g vs 0 μg/g). Increased concentrations of Tα 1 were not detected in the brain and skeletal muscle tissues. These pharmacokinetic studies of Tα 1 in mice indicate that rapid renal excretion of Tα 1 represents a major source of humoral loss following IP administration. Recent preliminary studies in humans confirm that the kidney rapidly releases high levels of Tα 1 in urine in a time frame consistent with that observed in mice.