Interactive effects of cadmium and Microcystis aeruginosa (cyanobacterium) on the growth,antioxidative responses and accumulation of cadmium and microcystins in rice seedlings

Ecotoxicology - Cadmium pollution and harmful cyanobacterial blooms are two prominent environmental problems. The interactive effects of cadmium(II) and harmful cyanobacteria on rice seedlings...     

Disturbed ion balance in flounder, Platichthys flesus L. exposed to sublethal levels of cadmium

The ion balance in the flounder (Ptatichthys flesus L.) was studied after 4 and 9 wk of exposure to sublethal cadmium levels (5–500 μg Cd/l) in brackish water. The cadmium exposure had no effect on the major blood plasma electrolytes, sodium and chloride, indicating an intact osmoregulation. In contrast, cadmium seriously affected the regulation of other ions. Potassium and calcium concentrations showed a strong and dose-dependent depression in blood plasma, whereas the plasma concentrations of inorganic phosphate and magnesium were significantly elevated. It is suggested that these ion disturbances might be associated with cadmium-induced pathological changes in ion-regulating tissues. The reduced concentrations of plasma calcium and potassium might be responsible for neuromuscular disturbances, such as hyperexcitability, spasms and tetanic body contractions, observed in some flounders exposed to the highest cadmium concentration (500 μg Cd/l). In spite of the pronounced disturbance of the calcium metabolism, the spinal columns of the cadmiumexposed flounders did not show any signs of demineralization, fractures or other deformations. This might be due to the fact that the flounder probably has an acellular bone tissue, which only to a small degree seems to be affected by the disturbed calcium balance. It is suggested that fish species with acellular bone tissue run a minor risk of suffering from skeletal damage after cadmium exposure than fish species with an active cellular bone tissue.     

Interaction between accumulation of cadmium selenium in the tissues of turbot Scophthalmus maximus

The interaction between accumulation of waterborne cadmium and selenite in juvenile turbot, Scophthalmus maximus, was investigated in the laboratory. Intestine, kidney and liver of turbot exposed to 150 μg Cd 1⁻¹ accumulated cadmium linearly with time over 5 wk at rates of 0.50, 0.014 and 0.11 μg Cd g⁻¹ dry wt. d⁻¹, respectively. Gills, skin and muscle reached steady-state cadmium levels of ca. 15, 0.8 and 0.25 μg Cd g⁻¹ after 1–3 wk of exposure. Plasma and erythrocytes reached steady-state concentrations of ca. 0.1 and 1–2 μg Cd ml ⁻¹ after 1–2 wk of exposure. Exposure to 105 μg Se-SeO₃²⁻1⁻¹ did not consistently alter selenium concentrations in gills, skin, liver, muscle and erythrocytes of juvenile turbot. Kidneys accumulated selenium linearly (0.029 μg Se g⁻¹ dry wt. d⁻¹) with time over 5 wk, while intestine reached a steady-state level after 2 wk. Selenium concentrations in the plasma were maintained close to the ambient level throughout the exposure time. Concurrent exposure to selenite augmented cadmium accumulation rates in gills, kidney and liver and reduced cadmium accumulation in intestine and erythrocytes; cadmium accumulation in spleen, skin, muscle and plasma was not affected. Concurrent exposure to cadmium depleted erythrocytes and partly skin of selenium and reduced accumulation of selenium in kidney and plasma, whereas selenium accumulation patterns in gills, intestine, liver, muscle and spleen were not affected by exposure to cadmium.     

Protective effect of quercetin on experimental chronic cadmium nephrotoxicity in rats is based on its antioxidant properties

Oxidative stress can play a key role in Cd-induced dysfunctions. Quercetin is a potent oxygen free radicals scavenger and a metal chelator. Our aim was to study the effect of quercetin on Cd-induced kidney damage and oxidative stress as well as its mechanism of action. Wistar rats were distributed in four experimental groups: control rats; Cd; quercetin and Cd + quercetin. Renal toxicity was evaluated by measuring urinary excretion of proteins, albumin, glucose and enzymes markers of tubular necrosis, as well as plasma concentration of creatinine. Plasma TBARS concentration and activity of antioxidant enzymes in kidney were also measured. Renal cell damage was assessed by electron microscopy. Animals that received both Cd and quercetin showed a better renal function than those receiving Cd alone. Cd-induced tubular lesions were markedly reduced in rats that also received quercetin. Cd-induced increase in plasma TBARS was prevented by the administration of quercetin. Total plasma antioxidants and renal superoxide dismutase and glutathione-reductase activities were higher in the group that received Cd and quercetin than in rats that received Cd alone. Quercetin administration does not modify the renal content or the urinary excretion of Cd. In conclusion, quercetin treatment prevents renal tubular damage and increased oxidative stress induced by chronic Cd administration, most probably throughout its antioxidant properties.     

Mass spectrometric detection and quantification of nodularin-R in flounder livers

Livers of flounders caught during August 1995 from the western Gulf of Finland and the Archipelago Sea were analyzed for nodularin-R (NODLN) by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and liquid chromatography-electrospray ionization-mass spectrometry (LC-MS). Results showed that NODLN was detected in samples by both MS techniques. NODLN content in samples varied between 0.082 and 0.637 microg g(-1) wet weight by LC-MS. Biotransformation products such as glutathione adduct were not found in the samples. The results showed that intact NODLN can be found in tissues after storage at -70 degrees C for several years.     

小鼠孕期染镉对子代免疫功能的影响

小鼠在受孕第９～１５天给予氯化镉灌胃，剂量分别为０，１．０，１０．０ｍｇ／ｋｇ，检测其仔鼠在４和８周龄对各项免疫功能的变化。结果发现，从时间上来看，仔鼠外周血白细胞总数、Ｔ淋巴细胞计数和血清溶血素滴度在８周龄时低剂量组有刺激作用，在４周龄时均无影响，表现出迟发作用；从剂量上看，８周龄时上述指标均为低剂量有刺激作用，高剂量无影响。而血清溶菌酶是在４周龄时高剂量组有抑制趋势。母鼠产后２１天肝肾内有明显的镉蓄积，仔鼠胸腺、脾、肝、肾中却未见明显镉蓄积，说明镉对仔鼠免疫功能的影响不是直接作用所致     

Protective effects of selenium (Se) and zinc (Zn) on cadmium (Cd) toxicity in the liver and kidney of the rat: histology and Cd accumulation

To assess the co-effect of Se and Zn on Cd accumulation in the liver and kidney and on their histology, male rats were exposed either to Cd, Cd+Zn, Cd+Se, or Cd+Zn+Se in their drinking water, during 35 days. Exposure to Cd resulted in its accumulation in the liver and kidney. In the Cd-Zn and Cd-Zn-Se groups, Cd contents in the two organs were significantly (p < 0.01) higher than those in the Cd group. Se did not induce any significant difference in hepatic and renal concentrations of Cd in comparison to Cd-treated group. Light microscopic examination indicated severe histological changes in the two organs under Cd influence. Se or Zn partially alleviated the damage observed in the liver. The same effect was remarked in the kidney with Se, but no differences in the renal histological structure have been observed between the Zn-Cd and the control groups. With Se and Zn simultaneous treatment during Cd exposure, the observed morphological changes had practically disappeared from the liver, but were only reduced in the kidney. CONCLUSION: Se and Zn can have a cooperative effect in the protection against Cd-induced structural damage in the liver but not in the kidney.     

Effect of cadmium on Japanese encephalitis virus infection in mice. 1. Acute and single-dose exposure experiment

When mice were treated with 0.09 mg cadmium chloride (Cd) per mouse once and inoculated i.p. simultaneously with Japanese encephalitis virus (JEV) they showed a significant difference in the incubation time and mortality between the treated and untreated groups in repeated experiments. Cd treatment shortened the incubation time and the mortality increased greater than twice compared with the untreated control. This effect was not observed in the case of intracerebral inoculation of JEV. Effects of Cd on antibody formation in mice were also determined. Animals given a single s.c. dose of Cd were immunized with JE inactivated vaccine once simultaneously. When mice were treated with Cd, they did not show low neutralizing and hemagglutination inhibition activities compared with the control mice. Pretreatment of Cd did not affect any mortality or antibody formation.     

Comparative study of bioconcentration and EROD activity induction in the Japanese flounder, red sea bream, and Java medaka exposed to polycyclic aromatic hydrocarbons

Japanese flounder (Paralichthys olivaceus), red sea bream (Pagrus major), and Java medaka (Oryzias javanicus) were exposed to water borne polycyclic aromatic hydrocarbons (PAHs) for 10 days to compare PAH bioconcentration and P450 enzyme induction by ethoxyresorufin-O-deethylase (EROD) activity for use in oil spill biomonitoring in Asian waters. Target exposure concentration for phenanthrene, pyrene, and chrysene were 30 microg/L each, while benzo[a]pyrene was 3.0 microg/L. Phenanthrene and pyrene were accumulated in the flounder and red sea bream; chrysene was found only in the livers of the red sea bream, while Java medaka accumulated the high molecular weight benzo[a]pyrene along with the other PAHs. Total PAH concentrations increased with duration of exposure in the red sea bream from 184+/-37 ng/g wet weight (w.w.) in day 2 to 572+/-72 ng/g (w.w.) in day 10; It, however, decreased in the other two species. Among the three fish species, Java medaka had the highest initial total PAH concentration of 388+/-62 ng/g (w.w.); this was, however, reduced to the lowest final concentration of 52.3+/-3 ng/g (w.w.). It also had the highest EROD activity of 4.2+/-2.8 n mol/min/mg protein compared to the lowest of 0.11+/-0.03 n mol/min/mg protein in the Japanese flounder. Java medaka with high EROD activity induction and bioaccumulation of all PAHs will be suitable for PAH biomonitoring in Asian waters. Due to its high PAH bioconcentration red sea bream is also recommended for consideration for biomonitoring and PAH chronic toxicity tests.     

Relationship between the development of hepato-renal toxicity and cadmium accumulation in rats given minimum to large amounts of cadmium chloride in the long-term: preliminary study

We wished to clarify the relationship between the sensitivity to induce hepato-renal toxicity and the level of cadmium (Cd) in the organs of rats exposed to minimum to large amounts of cadmium chloride (CdCl₂). For this purpose, groups of female Sprague-Dawley (SD) rats, each consisting of 24 animals, were fed diet containing CdCl₂ at concentrations of 0, 8, 40, 200, and 600 ppm for 2, 4, and 8 months from 5 weeks of age. All surviving rats given 600 ppm Cd were killed at 4␣months because of deterioration of their general condition. Animals of this group showed anemia and decreased hematopoiesis in the bone marrow, in addition to reduction of cancellous bone in their femurs. Hepatotoxicity was observed after 2 months in the groups treated with 200 ppm. By 4 months, the rats in the 600 ppm group had developed periportal liver cell necrosis. Renal toxicity characterized by degeneration of proximal tubular epithelia was apparent in the groups treated with 200 ppm from 2 months, becoming more prominent in the high-dose rats at 4 months. Hepatic accumulation of Cd increased linearly with the duration of treatment. In contrast, the concentration of Cd in the renal cortex of rats treated with 600 ppm reached a plateau level of ∼250 μg/g within the first 2 months. The renal concentration of Cd in the 200 ppm group when renal toxic lesions were first detected at 2 months ranged from 104 to 244 μg/g. No renal lesions were observed in the 40 ppm group after 8 months, despite the presence of 91–183 μg/g of Cd in the kidneys. The results thus suggest that renal toxicity would not be induced by treatment with minimum amounts of CdCl₂ for periods longer than 8 months, although accumulation of Cd might gradually progress. A further 2-year feeding study of CdCl₂ and Cd-polluted rice is now in progress. Received: 26 January 1998 / Accepted: 26 May 1998     

Biochemical evaluation of antihyperglycemic and antioxidative effects of Morinda citrifolia fruit extract studied in streptozotocin-induced diabetic rats

The hypoglycemic and antioxidative effects of Morinda citrifolia fruit extract were evaluated in streptozotocin (STZ)-induced diabetic rats. The ethanolic extract of Morinda citrifolia fruit at a concentration of 300 mg/kg body weight/rat/day was orally administered to STZ-induced diabetic rats for a period of 30 days. The elevated levels of blood glucose, glycosylated hemoglobin, blood urea, and serum creatinine in the diabetic rats reverted back to near normal after treatment with the noni fruit extract. Similarly significant decrease in the levels of plasma insulin and hemoglobin were elevated to near normal after treatment with fruit extract, suggesting the antihyperglycemic effect of Morinda citrifolia fruit. Determination of thiobarbituric acid reactive substance (TBARS), hydroperoxides, and both enzymatic and nonenzymatic antioxidants evidenced the antioxidative potential of the extract of noni fruit, which in turn may be responsible for its hypoglycemic potential. Alterations observed in the activities of pathophysiological enzymes such as serum aspartate transaminase (AST), serum alanine transaminase (ALT), and serum alkaline phosphatase (ALP) in the serum of control and experimental groups of rats revealed the tissue protective nature of Morinda citrifolia fruits, and the results of all the biochemical parameters analyzed were comparable with glyclazide, the standard reference drug.     

Mechanism for the decrease in the accumulation of cadmium (Cd) in Cd-resistant Chinese hamster V79 cells

The mechanism for the decrease in the accumulation of cadmium (Cd) in Cd-resistant Chinese hamster V79 (Cd^r) cells in culture was investigated in a comparison with Cd-sensitive (Cd^s) cells. Both Cd^r and Cd^s cells took up Cd in a time-dependent manner but the rate of uptake of Cd by Cd^r cells was about 15% of that by Cd^s cells. Kinetic studies of the uptake of Cd showed that the V_max values for Cd^r and Cd^s cells were 0.31 and 0.46 pmol Cd/h per mg protein, respectively. The K_m values were 31.95 μM for Cd^r cells and 3.15 μM for Cd^s cells. Mersalyl acid, a sulfhydryl (SH) blocker to which cells are impermeable, inhibited the uptake of Cd by Cd^s cells at subtoxic concentrations while Cd^r cells were insensitive to inhibition by mersalyl acid, suggesting that SH groups in the plasma membrane play a role in the uptake of Cd. Uptake of Cd by Cd^s cells was dependent on the pH of the incubation medium and the rate of uptake was very high at pH 7.4 and pH 8.0 relative to the rates at pH 6.0 and pH 6.8. By contrast, the uptake of Cd by Cd^r cells was lower at all pH values than that by Cd^s cells. The decrease in the rate of uptake of Cd by Cd^r cells could not be ascribed to an increase in the efflux of Cd. A Cd-blotting technique was used to detect plasma membrane proteins with high affinity for Cd. Two major differences in terms of Cd-binding proteins (Cd-BPs) were observed between Cd^r and Cd^s cells. A 110-kDa Cd-BP, detected in Cd^s cells, was found at a reduced level in Cd^r cells, while an 82-kDa Cd-BP, which was not observed in Cd^s cells, was detected in Cd^r cells.     

Hematobiochemical effects of cadmium intoxication in male Japanese quail (Coturnix japonica) and its amelioration with silymarin and milk thistle

The present study was designed to investigate the toxico-pathological effect of cadmium (Cd) and its amelioration with silymarin (SL) and milk thistle (MT) in male Japanese quail (Coturnix japonica). A total of 144 male quail were divided into nine equal groups (A–I). Experimental feeds were offered to these groups containing different combinations of Cd chloride (Cd1: 150 and Cd2: 300?mg/kg feed), SL (250?mg/kg of feed), and MT (10?g/kg of feed). The duration of the experiment was 60 days. The physical parameters studied included feed intake and body weight. Hematobiochemical parameters included total protein, albumin, ALT, AST, creatinine, urea, hemoglobin, and hematocrit. The data were analyzed by analysis of variance (ANOVA) technique, and group means were compared by Duncan’s multiple range test. The body weight decreased significantly in Cd-treated groups while SL and MT ameliorated the toxic effects of Cd as compared to control group. The hemoglobin (Hb) concentration and hematocrit (Hct) values were decreased significantly in Cd2-treated group, while Hb and Hct decreased nonsignificantly in Cd1-treated group compared with control. Similar hematological findings were observed, when Cd was used in combinations with SL and MT. Urea, creatinine, and AST increased significantly, while ALT increased nonsignificantly in Cd-treated groups as compared to control group, while total protein, albumin, and globulin decreased significantly in Cd-treated groups as compared to control group. The SL and MT completely ameliorated these toxic effects at low dose of Cd; however, amelioration was partial at higher doses of Cd. These compounds (SL &; MT) might be used to ameliorate toxic effects of Cd in Japanese quail.     

乙型脑炎病毒E315回复突变对小鼠神经毒力的影响

目的  构建乙型脑炎病毒减毒株SA14-14-2 囊膜蛋白第315位氨基酸（E315）回复突变株,并分析该位点回复突变后在小鼠体内的神经毒力变化。方法  采用重叠PCR扩增含基因组第1921核苷酸位点回复突变的基因片段,替换SA14-14-2全长克隆的相应区域,获得回复突变株M315。通过测定突变株的蚀斑大小和一步生长曲线并与SA14-14-2进行比较,分析M315的增殖特征;采用小鼠模型测定该突变株的脑内神经毒力、皮下感染入脑能力、腹腔感染入脑能力和乳鼠传代返祖,分析疫苗株E315位点回复突变后毒力的变化。结果  成功构建了回复突变株M315,其蚀斑大小和增殖特征与疫苗株相似。M315对17~19日龄小鼠无皮下或腹腔入脑神经毒力,鼠脑病毒有很低但可检测的脑内神经毒力（小于3.0 lg蚀斑形成单位（plaque forming unit,PFU） / 0.03 ml）,皮下注射不发病。3~5日龄乳鼠脑内接种后发病,但脑内病毒毒力低于3.0 lgPFU / 0.03 ml。结论  在分子水平上证明了E315位点是影响乙型脑炎疫苗安全性的关键位点之一,但影响较弱。E315位点的回复突变虽使SA14-14-2的小鼠脑内神经毒力和乳鼠传代返祖能力增强,但没有超出中国药典规定的毒力范围。     

The effects of drugs and denervation on removal and accumulation of noradrenaline in the perfused hind-limb of the dog

Summary The removal of noradrenaline by the autoperfused hind-limb of dogs anaesthetized with pentobarbital, as well as the accumulation of noradrenaline in the saphenous vein were studied. Sensitivity of the perfused vascular area was determined by the response of the perfusion pressure to infusions of noradrenaline.The removal of noradrenaline declined very slowly during infusions lasting for up to 2 h, but edema of the perfused limb occurred after 45 to 60 min; therefore, the duration of infusion was limited to 30 min. During this period, noradrenaline was infused in rates increasing by a factor of 2 and ranging from 0.5 to 16 g/kg per minute. Accumulation capacity was saturated at 1 g/kg · min^–1, but the amount removed increased until a four-to eightfold rate was reached and then levelled off.At a rate of 1 g/kg · min^–1 the influence of drugs and of surgical denervation was investigated in other experimental series. Cocaine, nialamide, phenoxybenzamine and pretreatment with reserpine reduced removal (by 50, 45, 40 and 35%, respectively). Cortexone had no detectable influence on removal with this rate of infusion, but blocked it effectively when 4 g/kg · min^–1 were infused. Accumulation of noradrenaline in the vein was prevented by cocaine or reserpine, slightly reduced by phenoxybenzamine and enhanced by nialamide. The effects of nialamide plus cocaine did not differ significantly from those of cocaine alone, but cortexone plus cocaine completely blocked removal and accumulation. Surgical denervation reduced removal by about 70% and abolished accumulation; reserpine plus nialamide had similar effects. In the case of nialamide, removal progressively diminished during the infusion period and this time dependence of effects was accompanied by a prolongation of noradrenaline washout.Cocaine, reserpine and denervation caused supersensitivity of the perfused vessels to noradrenaline, whereas nialamide and cortexone had no such effect and phenoxybenzamine caused subsensitivity.The pronounced ability of the perfused vessels of the hind-limb to remove noradrenaline from the circulating blood is attributed primarily to neuronal uptake and intraneuronal oxidative deamination; extraneuronal uptake and inactivation seem to play an important role when neuronal mechanisms are saturated (infusion of higher noradrenaline doses) or impaired (after cocaine or denervation).Supported by Instituto de Alta Cultura (Research Project PMC/2). Part of this work was presented at the Fifth International Congress on Pharmacology (S.Francisco, July 23–28, 1972).     

临床药代动力学中蓄积指数的计算方法及其评价

目的 多次给药的蓄积一般由药动学的蓄积指数（Rac）来表达,但计算Rac有多种方法,本文对此进行分析和评价,以确定合理的方法。方法 计算机模拟蒿乙醚真实实验的单、多次给药的血药浓度经时变化,分别采用AUC法、Cmax法、Ctrough法和模型法计算Rac,采用Bootstrap抽样法评价各法的优缺点及适用条件。结果 AUC法和Cmax法较Ctrough法和模型法更为稳定,模型法计算值偏高。药效或毒性呈浓度信赖性者,宜用Cmax法,而药效或毒性时间信赖性和体内药量信赖性时,宜用AUC法。结论 药物蓄积与有效性和安全性均相关,Rac计算方法需根据药物特性进行合理选择。     

Allergy medication in Japanese volunteers: treatment effect of single doses on nocturnal sleep architecture and next day residual effects

ABSTRACT

Objectives: To evaluate the acute effects of two histamine H1-receptor antagonists on nocturnal sleep architecture and on next day cognitive function and psychomotor performance.

Methods: This was a single-site, randomized, double-blind, 3-way crossover study, comparing the effects of a single dose of chlorpheniramine (6?mg), fexofenadine (120?mg) and placebo in 18 healthy (male and female) Japanese volunteers aged 20–55 years. Volunteers were resident for 3 days and each period was separated by a minimum 5‐day washout period. The three treatments were administered at 23.00?h. Overnight sleep was measured from 23.00?h to 07.00?h using polysomnography. Residual effects were studied at 07.00?h and 9.00?h the next morning, with the latency to sleep (sleep latency test) measured at 09.30?h.

Results: Compared with placebo, chlorpheniramine increased the latencies to sleep onset and rapid eye movement (REM) sleep (?p ≤ 0.05 for both), and reduced the duration of REM sleep (?p ≤ 0.01), but this was not observed with fexofenadine. As far as residual effects the next morning were concerned there were decrements in performance with chlorpheniramine, but not with fexofenadine. Chlorpheniramine 6?mg impaired divided attention (?p < 0.001), vigilance (?p < 0.05), working memory (?p < 0.0001) and sensori-motor performance (?p < 0.01), and the latency to daytime sleep was reduced (?p < 0.0001). Six adverse events possibly related to study medication were reported during the study, three of which were related to placebo, two to fexofenadine and one to chlorpheniramine.

Conclusion: These findings suggest that a single nocturnal dose of fexofenadine has advantages over the first-generation antihistamine chlorpheniramine, being free of disruption of night-time sleep and detrimental effects on cognitive performance the next day. It is likely that this advantage will remain with chronic ingestion, but this would need to be confirmed.     

Influence of humic substances on the toxic effects of cadmium and SDBS to the green alga Scenedesmus obliquus

The joint toxicity of chemicals mixture in the aquatic environment was still not well clear. To clarify the joint toxicity of the mixtures of metals and organic pollutants, as well as the influence of dissolved organic matter (DOM) in field water-body on their toxic effects, we conducted the toxicity tests with cadmium (Cd) and sodium dodecyl benzene sulfonate (SDBS) on Scenedesmus obliquus (S. obliquus) with or without the presence of fulvic acid (FA), a typical of DOM. Our results showed Cd was more toxic to S. obliquus than SDBS, and the effects of fulvic acid on SDBS were greater than Cd. The joint toxicity of Cd and SDBS expressed a synergistic effect on S. obliquus, which was observed to be increased with the presence of FA. Our results gave an example for the joint toxicity investigations of organics and metals, aiding to understanding the toxicity of pollutant mixtures in field water bodies containing DOM.     

Limited frequency of the CYP2C19*17 allele and its minor role in a Japanese population

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
• A novel CYP2C19 gene variant, CYP2C19 * 17 , is associated with increased metabolic activity.
• Ethnic differences in the frequency of the variant allele have been reported. However, the frequency of the CYP2C19 * 17 allele has not been studied in the Japanese population.
WHAT THIS STUDY ADDS
• In a population of 265 healthy Japanese subjects, a low frequency (1.3%) of the CYP2C19 * 17 allele was observed.
• The limited frequency of the * 17 allele and the absence of a subject homozygous for * 17 indicated that CYP2C19 * 17 would play a minor role in a Japanese population.  

AIMS

We investigated the CYP2C19 * 17 allelic frequency in Japanese subjects, and evaluated whether CYP2C19 * 17 is an important determinant of interindividual variability of CYP2C19 activity.  

METHODS

We enrolled 265 subjects to determine their CYP2C19 genotype and plasma metabolic ratio following a single dose of 40 mg omeprazole.  

RESULTS

Seven subjects heterozygous for CYP2C19 * 17 and no * 17/ * 17 subjects resulted in the CYP2C19 * 17 frequency being 1.3%. These heterozygotes had moderate metabolic activities when compared with the metabolic ratio of the other subjects.  

CONCLUSIONS

The low frequency of CYP2C19 * 17 and the absence of * 17/ * 17 indicates that CYP2C19 * 17 plays a minor role in the Japanese population.