Sun-In Moon

Temporal changes in urinary levels of cadmium, N-acetyl-β-d-glucosaminidase and β2-microglobulin in individuals in a cadmium-contaminated area

Cadmium (Cd) is a metal that is toxic to renal tubules. If renal tubules are damaged by Cd, urinary excretion of N-acetyl-β-D-glucosaminidase (NAG) and beta 2-microglobulin (β2-MG) increases. The aim of this study was to describe the changing patterns of urinary Cd, NAG, and β2-MG levels over a 3-year period in individuals living in a Cd-contaminated area. This follow-up study included 191 residents (65.6±9.3 years) who were living in the vicinity of a copper refinery. Urinary levels of Cd, NAG activity, and β2-MG levels were measured, and their determinants and changing patterns were analyzed statistically. The natural logarithm of urinary Cd levels decreased significantly over time. Sex and intake of locally cultivated rice were significant determinants of urinary Cd concentration. Urinary NAG activity decreased over time. Age and urinary Cd concentration were significant determinants of urinary NAG activity in subjects with urinary Cd concentrations >5μg/g creatinine. In subjects whose urinary Cd concentrations were >2μg/g creatinine, diabetes was found to be a significant risk factor for high urinary NAG activity. The slope for temporal changes in urinary β2-MG levels was negative in subjects whose urinary Cd levels were <2μg/g creatinine but was positive in those whose urinary Cd levels were 2-5μg/g creatinine or >5μg/g creatinine. The urinary β2-MG levels found in individuals whose urinary Cd levels were >2μg/g creatinine suggest that previous Cd-induced renal tubular damage had occurred.

Differences in the susceptibility to cadmium-induced renal tubular damage and osteoporosis according to sex

This study aimed to estimate the risks for renal tubular damage and osteoporosis in individuals with long-term environmental Cd exposure. This cross-sectional study comprised 1086 residents living in the vicinity of a copper refinery plant. As the urinary Cd levels increased, the proportion of female subjects with β₂-MG ≥300 μg/g creatinine also increased significantly, but this was not observed in the male subjects. The prevalence of osteoporosis was significantly higher in men with urinary Cd >5 μg/g creatinine than in those with urinary Cd ≤5 μg/g creatinine. This difference was not observed in the corresponding female groups. The association between increased urinary excretion of β₂-MG and decreased BMD was statistically significant only in the female subjects. We suggest that an increased Cd body burden directly decreases the BMD in male subjects; however, in female subjects, it first induces renal microtubular damage, which can lead to osteoporosis.

Thiobarbituric Acid Reactive Substances Levels in Brain Tissue of Aldh2 Knockout Mice Following Ethanol Exposure for 8 Weeks

과다한 음주는 알츠하이머 및 파킨슨 질병과 같은 각종 만성 퇴행성 뇌질환의 대표적인 원인 중 하나로 알려져 있다. 체내에 유입된 에탄올은 알코올 탈수소효소(alcohol dehydrogenase, ADH)에 의해 아세트알데히드로 대사된 후 다시 알데히드탈수소효소 2(aldehyde dehydrogenase 2, ALDH2)에 의해 아세트산으로 대사되어 배출된다. 에탄올의 대사과정 중에는 다량의 free radical이 생성되어 체내에서 산화적 스트레스를 유발하는 것으로 알려져 있고, 아세트알데히드는 활성산소를 생산하는 독성물질로 잘 알려져 있다. 본 연구에서는 8주간 에탄올에 노출된 Aldh2 knockout 마우스를 사용하여 ALDH2 효소 활성이 뇌 조직과 소변의 지질과산화에 미치는 영향에 대하여 살펴보았으며, 지질과산화 정도를 측정하기 위해 HPLC를 통한 TBARS 정도를 측정하였다. 연구결과, 마우스에서 만성 에탄올 섭취는 뇌 조직 TBARS 생성에 영향을 주지 않는 것으로 나타났으나, 소변 TBARS는 Aldh2 (-/-) 마우스에서 에탄올을 투여함에 따라 유의한 증가를 보였다(p 【Excessive alcohol consumption causes various degenerative brain diseases including Alzheimers disease and Parkinsons disease. Absorbed ethanol is metabolized to acetaldehyde and acetic acid by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Acetaldehyde is well known as a toxicant through generation of reactive oxygen species (ROS). Therefore, ALDH2 activity may play important roles in the pathogenesis of alcohol-induced brain diseases. In this study, we demonstrated the effects of ALDH2 enzyme activity on lipid peroxidation in brain tissues and urine of mice exposed to ethanol for 8 weeks. Five male, 8-week old Aldh2 (+/+) and Aldh2 (-/-) mice (C57BL/6J strain) in each group were exposed to ethanol for 8 weeks (2 g/kg wt./day) using gavage, and those in the control group received 0.9% saline alone. Thiobarbituric acid reactive substances (TBARS) level, a marker for lipid peroxidation, was measured in whole brain tissue and urine by high performance liquid chromatography. As a result, chronic ethanol treatment did not show any statistical change on the TBARS level of brain tissue in both Aldh2 (+/+) mice and in Aldh2 (-/-) mice. However, following ethanol exposure for 8 weeks in Aldh2 (-/-) mice, the urinary TBARS levels were significantly increased to more than double compared to the pretreatment group. This result was not observed in Aldh2 (+/+) mice. These results suggest that although ALDH2 enzyme activity plays a role in the generation of ROS in the whole body, it does not seem to be important in the pathogenesis of alcohol induced degenerative brain diseases.】

Effect of ALDH2 Enzyme Activity on the Level of 8-Hydroxydeoxyguanosine in Tissues Following Ethanol Exposure

Individuals who regularly consume excessive quantities of alcohol are at a greater risk of developing various cancers such as esophageal, pharyngeal and lung cancers compared to normal populations if they are deficient in ALDH2 enzyme activity. We evaluated oxidative DNA damage in the liver, brain, and lung tissues of Aldh2 +/+ and Aldh2 -/- mice after they had been subjected to acute ethanol exposure. The 8-hydroxydeoxyguanosine (8-OHdG) level in each tissue was evaluated as a biomarker of oxidative DNA damage. The 8-OHdG level in the liver, brain, and lung tissues was significantly increased following ethanol treatment. In addition, the level of 8-OHdG in the liver and lung tissues was affected by ALDH2 enzyme activity. This result suggests that ALDH2-deficient individuals may be more susceptible than wild-type ALDH2 individuals to ethanol-mediated diseases, including cancer.

Novel Method for Urinary 1-Hydroxypyrene Measurement Using Molecular Imprinting

This study was performed to determine whether or not urinary 1-hydroxypyrene (1-OHP) levels can be accurately detected by our 1-OHP-detecting -Bead-HPLC assay that we developed based on the molecular imprinting method. Our method showed a variation coefficient of 4.97% and a between-day variation coefficient of 4.43%, suggesting that this may be a very stable method. In addition, the recovery rate of 1-OHP from a mixture of 1-OHP and similar substances using our -Bead-HPLC method was estimated to be 105.6%. The correlation coefficient between the conventional enzyme-HPLC method and this new method was 0.74 (p-coating beads and that development of beads by molecular imprinting can be applied to analysis of chemicals other than 1-OHP.

Amyloid-β Levels in Mice Hippocampus According to the ALDH2 Enzyme Activity followed Ethanol Exposure for 8-Weeks

Alzheimer`s disease (AD) is a progressive neurodegenerative disease, resulting in the loss of cognitive function. Mitochondrial aldehyde dehydrogenase (ALDH2) has been proposed to be a risk factor for the development of AD, but there is still controversy about that. In this study, we demonstrated the role of ALDH2 enzyme activity on amyloid-beta (A) and nuclear factor kappa B (NF-) expression in mice brain following ethanol exposure for 8 weeks. Five male Aldh2 (+/+) and Aldh2 (-/-) mice, 8 weeks-old of age (C57BL/6J strain), in each group were exposed to ethanol for 8 weeks (2 g/kg wt./day) using gavage. Those in the control groups received 0.9% saline alone. Results showed a difference in expression level of A in the hippocampus after ethanol exposure according to the ALDH2 enzyme activity (p). Our results suggest a possibility that ALDH2 enzyme activity may be an important role in the development of AD.Alzheimer’s disease (AD) is a progressive neurodegenerative disease, resulting in the loss of cognitive function. Mitochondrial aldehyde dehydrogenase (ALDH2) has been proposed to be a risk factor for the development of AD, but there is still controversy about that. In this study, we demonstrated the role of ALDH2 enzyme activity on amyloid-beta (Aβ) and nuclear factor kappa B (NF-κB) expression in mice brain following ethanol exposure for 8 weeks. Five male Aldh2 (+/+) and Aldh2 (-/-) mice, 8 weeks-old of age (C57BL/6J strain), in each group were exposed to ethanol for 8 weeks (2 g/kg wt./day) using gavage. Those in the control groups received 0.9% saline alone. Results showed a difference in expression level of Aβ in the hippocampus after ethanol exposure according to the ALDH2 enzyme activity (p<0.05), but not in the level of NF-κB. Our results suggest a possibility that ALDH2 enzyme activity may be an important role in the development of AD.