Change of serum L-tryptophan levels following the development and recovery of acute puromycin aminonucleoside nephrosis in rats

Abstract

Summary.It is known that total L-tryptophan (Trp) levels decrease with a decrease in albumin-bound Trp levels and an increase in free Trp levels in the plasma or serum of nephrotic children. We, therefore, examined the change of serum Trp levels following the development and recovery of acute nephrosis in 6-week-old male Wistar rats injected once with puromycin aminonucleoside (100mg/kg body weight) and checked the levels of 16 amino acids including Trp in the serum and the levels of Trp in the liver, kidney, and urine under nephrotic conditions. In this study, the development and recovery of nephrosis were checked by the changes of levels of urinary protein and serum protein and albumin. Total serum Trp and albumin-bound serum Trp levels decreased with the development of nephrosis and these decreased levels returned to the normal level with its recovery. In contrast, free serum Trp levels increased with the development of nephrosis and this increased level returned to the normal level with its recovery. In the serum of nephrotic rats, the decrease of albumin-bound Trp levels and the increase of free Trp levels were well consistent with a decrease in albumin levels and an increase in the level of non-esterified fatty acids which are known to weaken the binding of Trp to albumin and among 16 amino acids studied, only Trp showed a significant change in its levels. Trp levels increased in the liver and kidney but not in the urine under nephrotic conditions. These results indicate that the change of serum Trp levels should be c!osely related to the condition of nephrosis and that although serum Trp is lost under nephrotic conditions, the lost serum Trp is accumulated in the liver and kidney.

Possible Contribution of a Decrease in Serum Albumin Concentration to a Low Level of Blood L-Tryptophan in Nephrotic Rats.

“…The remaining Trp is available for protein synthesis in a variety of tissues and for serotonin synthesis in the brain (1). Unlike other amino acids, 80-90% of total Trp present in the plasma or serum of humans and animals normally occurs in an albumin-bound form, while the remainder et al (10-20%) circulates in a free form (i.e., an albumin-unbound form) (2)(3)(4)(5)(6) …”

Fate of Elevated L-Tryptophan in the Blood of Nephrotic Rats with Oral L-Tryptophan Administration in Their Body

“…The remaining Trp is available for protein synthesis in a variety of tissues and for serotonin synthesis in the brain (1). Unlike other amino acids, 80-90% of the total Trp present in the plasma or serum of humans and animals normally occurs in an albumin-bound form, while the remainder circulates in an albumin-unbound form, i.e., a free form (2)(3)(4)(5)(6)(7)(8)(9).…”

“…Puro mycin aminonucleoside (PAN) is well known to induce nephrosis resembling minimal change nephropathy with focal segmental glomerulosclerosis seen in humans (12,13). We have shown in rats treated once with PAN that the changes in the serum concentrations of total, albumin-bound, and free Trp are closely related to the severity of nephrosis and that total serum Trp concen tration is reduced with an increase in free serum Trp concentration under nephrotic conditions in which decreased concentrations of albumin and increased concentrations of non-esterified fatty acids (NEFA), which inhibits the binding of Trp to albumin, occur in the serum (7,8). We have also shown in rats with PAN nephrosis that Trp is accumulated in the liver and kid ney without being excreted into the urine (7).…”

“…We have shown in rats treated once with PAN that the changes in the serum concentrations of total, albumin-bound, and free Trp are closely related to the severity of nephrosis and that total serum Trp concen tration is reduced with an increase in free serum Trp concentration under nephrotic conditions in which decreased concentrations of albumin and increased concentrations of non-esterified fatty acids (NEFA), which inhibits the binding of Trp to albumin, occur in the serum (7,8). We have also shown in rats with PAN nephrosis that Trp is accumulated in the liver and kid ney without being excreted into the urine (7). Further more, we have shown that elevated Trp in the blood of PAN nephrotic rats with oral Trp administration disap pears more rapidly than that in normal rats without nephrosis under the same intestinal absorption of the administered Trp, and have suggested that this rapid disappearance of elevated Trp in the blood is due to decreased serum albumin concentration (8,9).…”