Effects of ADH1B and ALDH2 Genetic Polymorphisms on Alcohol Elimination Rates and Salivary Acetaldehyde Levels in Intoxicated Japanese Alcoholic Men.

BACKGROUND: The genetic polymorphisms of alcohol dehydrogenase-1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) are associated with the risk of alcoholism and upper aerodigestive tract cancer in alcoholics. Salivary ethanol (sEtOH) levels are well correlated with blood EtOH levels. METHODS: To study the effects of ADH1B and ALDH2 genotypes on the alcohol elimination rate (AER) and salivary acetaldehyde (sAcH) levels, we measured the sEtOH and sAcH levels twice at a 1-hour intervals in 99 intoxicated Japanese alcoholic men who had stopped drinking for 4 or more hours. RESULTS: The initial sEtOH levels did not differ between the ADH1B*2 group (n = 50) and the ADH1B*1/*1 group (n = 49) (median: 0.617 vs. 0.762 mg/ml). The salivary AER (sAER) increased as the sEtOH levels increased (p < 0.0001). After stratification according to the sEtOH levels (<0.4, 0.4 to 0.99, and ≥1.00 mg/ml), the median sAER of the ADH1B*2 group was 0.075, 0.188, and 0.228 mg/ml/h, respectively, and that of the ADH1B*1/*1 group was 0.037, 0.115, and 0.233 mg/ml/h, respectively. The sAER of the ADH1B*2 group was faster than that of the ADH1B*1/*1 group overall (p = 0.001) and when the sEtOH category was 0.4 to 0.99 mg/ml (p < 0.0001). The ADH1B genotype and the sEtOH levels had an interaction effect on the sAER (p = 0.036). A multiple linear regression analysis with a stepwise procedure selected the ADH1B*2 allele (p = 0.004) and the sEtOH levels (p < 0.0001) as positive predictors of sAER. The sAER did not differ according to the ALDH2 genotype. The sAcH levels were higher than the blood AcH levels reported in alcoholics, probably because of AcH production by oral microorganisms. The sAcH of the ALDH2*1/*2 group (n = 18) was higher than that of the ALDH2*1/*1 group (n = 81) overall (p = 0.0008) and when the corresponding sEtOH category was ≥1.00 mg/ml (median: 3.195 vs. 1.776 µg/ml, p = 0.009). A multiple linear regression analysis selected the ALDH2*1/*2 and the sEtOH levels as positive predictors of the sAcH levels (p < 0.0001). CONCLUSIONS: The enhanced AER in ADH1B*2 carriers and the increased sAcH levels in ALDH2*1/*2 carriers among intoxicated alcoholics provide possible mechanisms explaining how each genetic polymorphism affects the risk of alcoholism and upper aerodigestive tract cancer.

Genotoxicity evaluation of sesamin and episesamin.

Sesamin is a major lignan that is present in sesame seeds and oil. Sesamin is partially converted to its stereoisomer, episesamin, during the refining process of non-roasted sesame seed oil. We evaluated the genotoxicity of these substances through the following tests: a bacterial reverse mutation assay (Ames test), a chromosomal aberration test in cultured Chinese hamster lung cells (CHL/IU), a bone marrow micronucleus (MN) test in Crlj:CD1 (ICR) mice, and a comet assay using the liver of Sprague-Dawley (SD) rats. Episesamin showed negative results in the Ames test with and without S9 mix, in the in vitro chromosomal aberration test with and without S9 mix, and in the in vivo comet assay. Sesamin showed negative results in the Ames test with and without S9 mix. In the in vitro chromosomal aberration test, sesamin did not induce chromosomal aberrations in the absence of S9 mix, but induced structural abnormalities at cytotoxic concentrations in the presence of S9 mix. Oral administration of sesamin at doses up to 2.0g/kg did not cause a significant increase in either the percentage of micronucleated polychromatic erythrocytes in the in vivo bone marrow MN test or in the % DNA in the comet tails in the in vivo comet assay of liver cells. These findings indicate that sesamin does not damage DNA in vivo and that sesamin and episesamin have no genotoxic activity.

Ventral tegmental lesions reduce overconsumption of normally preferred taste fluid in rats.

Previous studies have suggested that the brain regions along the taste pathway and its anatomical interfacing with the brain reward system are concerned with palatability-induced consumption. To clarify whether the ventral tegmental area (VTA) is involved in the behavioral expression induced by taste pleasantness, we examined the effects of lesions to the VTA on the consumption of taste stimuli in rats. (1) Bilateral extensive electrolytic lesions to the VTA selectively reduced the consumption of a normally preferred taste fluid (0.1 M sucrose) compared to that of sham-operated animals during a 24-h two-bottle choice test. The consumption of other fluids, including non-preferred taste fluids (HCl and quinine hydrochloride) was not different between the lesioned and sham animals. (2) The injection of midazolam (3 mg/kg), a benzodiazepine agonist, or morphine (2 mg/kg) significantly increased the consumption of 0.1 M sucrose fluids in the sham animals. The same injections, however, failed to increase intake of the 0.1 M sucrose in rats with 6-hydroxydopamine lesions of the VTA. Neither midazolam nor morphine modified the intake of non-preferred quinine (0.0003 M) solution in both the lesioned and sham animals. These results suggest that dopaminergic mediation in the VTA is required to enhance the consumption of normally preferred fluids exclusively.

Effect of a soybean product on serum lipid levels in female university students.

1. A dietary intervention study targeting female students by using cake containing soybean protein and isoflavone was conducted. Female students (n = 120) were divided into three Groups (A, 6.26 g of soybean protein and isoflavone at 50 mg/day; B, 1.36 g soybean protein and isoflavone 50 mg; and C, a wheat puff as placebo). Intervention period was 4 weeks. The ratio of hypercholesterol in each group indicated a high value; A: 25%, B: 17.9% and C: 24.4%. 2. Total cholesterol as well as the rate of hypercholesterolemia decreased in Group A. The average total cholesterol significantly reduced (P < 0.001) from 242 +/- 17 to 220 +/- 25 mg/dL in Group A. 3. Dietary intake of soy protein for 4 weeks could be effective in reducing CHD risk among Japanese female students with a high plasma cholesterol level.