Affinity for α-tocopherol transfer protein as a determinant of the biological activities of vitamin E analogs

Abstractα-Tocopherol transfer protein (αTTP), a product of the gene which causes familial isolated vitamin E deficiency, plays an important role in determining the plasma vitamin E level. We examined the structural characteristics of vitamin E analogs required for recognition by αTTP. Ligand specificity was assessed by evaluating the competition of non-labeled vitamin E analogs and α-[3H]tocopherol for transfer between membranes in vitro. Relative affinities (RRR-α-tocopherol=100%) calculated from the degree of competition were as follows: β-tocopherol, 38%; γ-tocopherol, 9%; δ-tocopherol, 2%; α-tocopherol acetate, 2%; α-tocopherol quinone, 2%; SRR-α-tocopherol, 11%; α-tocotrienol, 12%; trolox, 9%. Interestingly, there was a linear relationship between the relative affinity and the known biological activity obtained from the rat resorption-gestation assay. From these observations, we conclude that the affinity of vitamin E analogs for αTTP is one of the critical determinants of their biological activity

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

We have previously reported that γ-tocopherol (γ-Toc) displays a natriuretic potency in rats fed a NaCl diet and administered 20 mg γ-Toc. In this study, we investigated whether γ-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 γ-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 (γ-CEHC) level, the sodium excretion content, and the urine volume were determined. The 24-hour γ-CEHC and sodium levels in the urine of the NaCl groups given 20 mg or 40 mg γ-Toc were significantly higher than those in the placebo group. The peak levels of urine sodium and γ-CEHC in the NaCl group given 40 mg γ-Toc appeared at 0–6 h, which was a more rapid increase than that seen in the group given 20 mg γ-Toc. The 24-hour urine volumes of the NaCl groups given 10 and 20 mg γ-Toc were significantly higher than the urine volume of the placebo group. Our findings suggested that γ-Toc increased sodium excretion in a dose-dependent manner in rats fed a NaCl diet. Moreover, a high dose of γ-Toc may accelerate its metabolism and cause an increase in the rate of sodium excretion

Clinical Characteristics and Outcomes in 314 Japanese Patients with Bacterial Endophthalmitis : A Multicenter Cohort Study from J-CREST

Bacterial endophthalmitis is an intraocular infection that causes rapid vison loss. Pathogens can infect the intraocular space directly (exogenous endophthalmitis (ExE)) or indirectly (endogenous endophthalmitis (EnE)). To identify predictive factors for the visual prognosis of Japanese patients with bacterial endophthalmitis, we retrospectively examined the bacterial endophthalmitis characteristics of 314 Japanese patients and performed statistics using these clinical data. Older patients, with significantly more severe clinical symptoms, were prevalent in the ExE group compared with the EnE group. However, the final best-corrected visual acuity (BCVA) was not significantly different between the ExE and EnE groups. Bacteria isolated from patients were not associated with age, sex, or presence of eye symptoms. Genus Streptococcus, Streptococcus pneumoniae, and Enterococcus were more prevalent in ExE patients than EnE patients and contributed to poor final BCVA. The presence of eye pain, bacterial identification, and poor BCVA at baseline were risk factors for final visual impairment

A proline-type fullerene derivative inhibits adipogenesis by preventing PPARγ activation

Obesity and its associated metabolic diseases represent some of the most rapidly expanding health issues worldwide, and, thus, the development of a novel chemical compound to suppress adipogenesis is strongly expected. We herein investigated the effects of water-soluble fullerene derivatives: a bis-malonic acid derivative and three types of proline-type fullerene derivatives, on adipogenesis using NIH-3T3 cells overexpressing PPARγ. One of the proline-type fullerene derivatives (P3) harboring three carboxy groups significantly inhibited lipid accumulation and the expression of adipocyte-specific genes, such as aP2, induced by the PPARγ agonist rosiglitazone. On the other hand, the bis-malonic acid derivative (M) and the 2 other proline-type fullerene derivatives (P1, P2), which have two carboxy groups, had no effect on PPARγ-mediated lipid accumulation or the expression of aP2. P3 fullerene also inhibited lipid accumulation induced by the combined stimulation with 3-isobutyl-1-methylxanthine (IBMX), dexamethasone, and insulin in 3T3-L1 preadipocytes. During the differentiation of 3T3-L1 cells into adipocytes, P3 fullerene did not affect the expression of C/EBPδ, C/EBPβ, or PPARγ, but markedly inhibited that of aP2 mRNA. These results suggest that P3 fullerene exhibits anti-obesity activity by preventing the activation of PPARγ

γ-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-α) has recently been proven to be a 2,7,8-trimethyl-2-(2'-carboxyethyl)-6-hydroxychroman (γ-CEHC), which is a metabolite of γ-tocopherol (γ-Toc). The purpose of this study was to investigate whether γ-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 γ-Toc group. After the oral administration of one experimental dose of 20 mg γ-Toc or placebo, rat urine was collected at 6 h intervals for 24 h, and then the urine volume, sodium and potassium and γ-CEHC content were determined. γ-Toc increased in the urine volume of the high-NaCl intake group. The sodium excretion in the high-NaCl group given γ-Toc was 8.29±2.20 g, while in the control group given γ-Toc it was 6.24±1.49 g fr om 12-18 h. In contrast, the potassium excretion in the rat urine did not change in any of the groups. Our findings suggested that γ-Toc accelerates the degree of sodium excretion in rats with a high sodium intake