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

Abstract

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.

Keywords: natriuretic hormone; sodium excretion; γ-CEHC; γ-tocopherol.

Fig. 1

γ-Tocopherol (γ-Toc) is metabolized to 2,7,8-trimethyl-2-(2'-carboxyethyl)-6-hydroxychroman (γ-CEHC), which is a natriuretic hormone.

Fig. 2

Changes in 2,7,8-trimethyl-2-(2'-carboxyethyl)-6-hydroxychroman (γ-CEHC) levels in rat urine after the oral administration of placebo or γ-tocopherol (γ-Toc). The rats were fed a vitamin E-deficient diet (control) or a NaCl diet for 4 weeks. In each group, one subgroup was administered a placebo, while the others were given 10 mg (γ10), 20 mg (γ20), 40 mg (γ40) of γ-Toc. After the oral administration of single dose of the placebo or γ-Toc, the rat urine was collected for 24 h (divided into 6 h periods) and then the γ-CEHC content was measured. The values are the mean ± SEM. of 4–6 rats, *p<0.05, **p<0.01 vs the control diet group at each time period.

Fig. 3

Correlation between the level of urine sodium and 2,7,8-trimethyl-2-(2'-carboxyethyl)-6-hydroxychroman (γ-CEHC) and γ-Toc. The rats were fed a control diet (closed circle) or NaCl diet (closed triangle) for 4 weeks. One subgroup was administered a placebo, while the others were given 10, 20, 40 mg of γ-Toc. A. Correlation between the urine sodium level and the level of 2,7,8-trimethyl-2-(2'-carboxyethyl)-6-hydroxychroman (γ-CEHC) throughout the 24 h period. These plots display a linear relationship at r² = 0.4139, p<0.001 (closed circle) and r² = 0.4199, p<0.001 (closed triangle). B. Correlation between the urine sodium level and the dose of γ-tocopherol (γ-Toc) throughout the 24 hour period. These plots display a linear relationship at r² = 0.0536 (closed circle) and r² = 0.1601 (closed triangle). C. Correlation between the level of 2,7,8-trimethyl-2-(2'-carboxyethyl)-6-hydroxychroman (γ-CEHC) and the dose of γ-tocopherol (γ-Toc) throughout the 24 h period. These plots display a linear relationship at r² = 0.2115, p<0.05 (closed circle) and r² = 0.4528, p<0.001 (closed triangle).

Fig. 4

Changes in the rat urine volume level after the oral administration of placebo and γ-tocopherol (γ-Toc). The rats were fed a vitamin E-deficient diet (control) or a NaCl diet for 4 weeks. In each group, one subgroup was a placebo, while the others were given 10 mg (γ10), 20 mg (γ20), 40 mg (γ40) of γ-Toc. After the oral administration of single dose of the placebo or γ-Toc, the rat urine was collected for 24 h (divided into 6 h periods) and the urine volume was determined. The values are the mean ± SEM of 4–6 rats, *p<0.05 vs placebo at each time period.

Fig. 5

Changes in the urine sodium levels after the oral administration of a placebo or γ-tocopherol (γ-Toc). The rats were fed a vitamin E-deficient diet (control) or a NaCl diet for 4 weeks. In each group, one subgroup was administered a placebo, while the others were given 10 mg (γ10), 20 mg (γ20), 40 mg (γ40) of γ-Toc. After the oral administration of single dose of the placebo or γ-Toc, the rat urine was collected for 24 h (divided into 6 h periods) and the sodium content was measured. The values are the mean ± SEM of 4–6 rats, *p<0.05, **p<0.01 vs placebo at each time period.

Fig. 6

Changes in the urine potassium content after the oral administration of placebo or γ-tocopherol (γ-Toc). The rats were fed a vitamin E-deficient diet (control) or a NaCl diet for 4 weeks. In each group, one subgroup was administered a placebo, while the others were given 10 mg (γ10), 20 mg (γ20), 40 mg (γ40) of γ-Toc. After the oral administration of single dose of the placebo or γ-Toc, the rat urine was collected for 24 h (divided into 6 h periods) and the potassium content was measured. The values are the mean ± SEM of 4–6 rats.