gamma-Tocopherol Accelerated Sodium Excretion in a Dose-Dependent Manner in Rats with a High Sodium Intake.

We have previously reported that gamma-tocopherol (gamma-Toc) displays a natriuretic potency in rats fed a NaCl diet and administered 20 mg gamma-Toc. In this study, we investigated whether gamma-Toc has natriuretic potency at a dose lower or higher than 20 mg in rats given a NaCl diet. Male rats were fed a control diet or a NaCl diet and administered either placebo or 10, 20 or 40 mg of gamma-Toc. The rat urine was collected for 24 hours (divided into 6 hour periods) and the 2,7,8-trimethyl-2-(2'-carboxyethyl)-6-hydroxychroman (gamma-CEHC) level, the sodium excretion content, and the urine volume were determined. The 24-hour gamma-CEHC and sodium levels in the urine of the NaCl groups given 20 mg or 40 mg gamma-Toc were significantly higher than those in the placebo group. The peak levels of urine sodium and gamma-CEHC in the NaCl group given 40 mg gamma-Toc appeared at 0-6 h, which was a more rapid increase than that seen in the group given 20 mg gamma-Toc. The 24-hour urine volumes of the NaCl groups given 10 and 20 mg gamma-Toc were significantly higher than the urine volume of the placebo group. Our findings suggested that gamma-Toc increased sodium excretion in a dose-dependent manner in rats fed a NaCl diet. Moreover, a high dose of gamma-Toc may accelerate its metabolism and cause an increase in the rate of sodium excretion.

Gamma-tocopherol enhances sodium excretion as a natriuretic hormone precursor.

Endogenous natriuretic factors are believed to be responsible for extracellular fluid homeostasis in mammals. A new endogenous natriuretic factor, Loma Linda University-alpha (LLU-alpha) has recently been proven to be a 2,7,8-trimethyl-2-(2'-carboxyethyl)-6-hydroxychroman (gamma-CEHC), which is a metabolite of gamma-tocopherol (gamma-Toc). The purpose of this study was to investigate whether gamma-Toc could accelerate sodium excretion into rat urine as a natriuretic hormone precursor. Male SD strain rats were divided into two groups; one was a control diet group, while the other was a high NaCl group (50 g/kg diet). Next, the two groups were each subdivided into two groups consisting of a placebo group and a gamma-Toc group. After the oral administration of one experimental dose of 20 mg gamma-Toc or placebo, rat urine was collected at 6 h intervals for 24 h, and then the urine volume, sodium and potassium and gamma-CEHC content were determined. gamma-Toc increased in the urine volume of the high-NaCl intake group. The sodium excretion in the high-NaCl group given gamma-Toc was 8.29+/-2.20 g, while in the control group given gamma-Toc it was 6.24+/-1.49 g from 12-18 h. In contrast, the potassium excretion in the rat urine did not change in any of the groups. Our findings suggested that gamma-Toc accelerates the degree of sodium excretion in rats with a high sodium intake.

Gamma-tocotrienol, a vitamin E homolog, is a natriuretic hormone precursor.

2,7,8-Trimethyl-2-(beta-carboxyethyl)-6-hydroxychroman (gamma-CEHC), a metabolite of gamma-tocopherol and gamma-tocotrienol, was identified as a new endogenous natriuretic factor. However, gamma-tocopherol and gamma-tocotrienol, both precursors of gamma-CEHC, have never directly been observed to have natriuretic potency. Thus, we investigated whether gamma-tocotrienol could cause natriuresis and diuresis in rats. The rats were divided into two groups that were given a control or a high-sodium diet for 4 weeks, and then subdivided into placebo and gamma-tocotrienol subgroups given only corn oil-removed vitamin E and oil supplemented with gamma-tocotrienol, respectively. After oral administration of three experimental doses, rat urine was collected and gamma-CEHC, urine volume, sodium, and potassium content were determined. Only in rats given a high-NaCl diet did gamma-tocotrienol accelerate and increase sodium excretion, showing no effect on potassium excretion. Sodium excretion in the high-NaCl group given gamma-tocotrienol was 5.06 +/- 2.70 g/day, and in the control group given gamma-tocotrienol, 0.11 +/- 0.06 g/day. Furthermore, gamma-tocotrienol affected urine volume in the specific condition of high-NaCl body stores and gamma-tocotrienol supplementation. In this study, we found that gamma-tocotrienol, one of the natural vitamin E homologs, stimulates sodium excretion in vivo, suggesting that gamma-tocotrienol possesses a hormone-like natriuretic function.