A non-invasive urine analysis method to determine the in-vivo flavin-containing mono-oxygenase (FMO) activity catalysing N-oxidation of ranitidine (RA) was developed and used to phenotype a Korean population. FMO activity was assessed by the molar concentration ratio of RA and RANO in the bulked 8 h urine. This method was used to determine the FMO phenotypes of 210 Korean volunteers (173 men and 37 women, 110 nonsmokers and 100 smokers). Urinary RA/RANO ratio, representing the metabolic ratio and the reciprocal index of FMO activity, ranged from 5.67-27.20 (4.8-fold difference) and was not different between men and women (P = 0.76) or between smokers and nonsmokers (P = 0.50). The frequencies of RA/RANO ratios were distributed in a trimodal fashion. Among the 210 Korean subjects, 93 (44.3%) were fast metabolizers, 104 (49.5%) were intermediate metabolizers and 13 (6.2%) were slow metabolizers. Subsequently, the relationship between the ranitidine N-oxidation phenotypes and FMO3 genotypes, determined by the presence of two previously identified mutant alleles (Glu158Lys: FMO3/Lys158 and Glu308Gly: FMO3/Gly308 alleles) commonly found in our Korean population was examined. The results showed that subjects who were homozygous and heterozygous for either one or both of the FMO3/Lys158 and FMO3/Gly308 mutant alleles had significantly lower in-vivo FMO activities than those with homozygous wild-type alleles (FMO3/Glu158 and FMO3/Glu308) (P < 0.001, Mann-Whitney U-test). Furthermore, the FMO activities of subjects with either FMO3/Lys158 or FMO3/Gly308 mutant alleles were almost identical to those having both FMO3 mutant alleles (FMO3/Lys158 and FMO3/Gly308). These two mutant alleles located, respectively, at exons 4 and 7 in the FMO3 gene appeared to be strongly linked by cis-configuration in Koreans. Therefore, we concluded that presence of FMO3/Lys158 and FMO3/Gly308 mutant alleles in FMO3 gene is responsible for the low ranitidine N-oxidation (FMO3 activity) in our Korean population.

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Lead (Pb) is a toxic heavy metal widely distributed in the environment. Recent studies suggest oxidative stress as one possible mechanism involved in Pb poisoning. The unicellular algae Chlorella vulgaris (CV) contains various bioactive substances with antioxidant for the prevention of oxidative stress by metals. We investigated the protective effects of CV on the oxidative system in five groups of male Sprague-Dawley rats fed American Institute of Nutrition (AIN)-76 diet, plus 2, 5 or 10% CV for 4 weeks. All animals were exposed to 200 mg/l lead acetate by drinking water except for the control (tap water). Body weight gains were significantly reduced in the Pb-exposed group (64%) relative to the control and CV groups. Brain weights were significantly increased in the Pb-exposed group (44%) relative to the others. In the experimental period, food intake, water intake and Pb intake were not different among the groups. The levels of Pb (87%) in brain obtained from the Pb-exposed group were significantly increased compared to the other groups. The levels of oxidative stress parameters in the brain such as superoxide dismutase (36%), glutathione peroxidase (63%), and glutathione reductase (30%) were decreased in the Pb-exposed group relative to the control but markedly increased in the CV groups. The CV also significantly increased glutathione levels by approximately 1.7-fold over the Pb-exposed group, while the malondialdehye concentration significantly decreased by approximately 47-71%. Based on these results, we found alterations in several indicators of oxidative stress of Pb intoxication, suggesting the antioxidant potential of CV. Therefore, CV may have protective effects on brain damage of low-level and short-term Pb exposure in the brains of rats.

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