Research progress on cold ischemia injury of steatotic donor livers / 器官移植

Liver transplantation is a vital treatment for end-stage liver disease. However, the shortage of donor livers has limited the development of liver transplantation. How to expand the source of donor livers has become a challenge in the academic community. In recent years, the proportion of donors with non-alcoholic fatty liver disease (NAFLD) has been increased. Rational use of steatotic donor livers is a feasible approach to expand the donor pool. Cold ischemia injury during donor liver preservation before liver transplantation increases the risk of postoperative organ dysfunction. Therefore, it is of significance to unravel the mechanism and intervention measures of cold ischemia injury of steatotic donor livers. Cold ischemia injury of steatotic donor livers is characterized as the damage of mitochondria, lysosomes and endoplasmic reticulum at the organelle level, and up-regulated expression of adenosine monphosphate activated protein kinase (AMPK), aldehyde dehydrogenase 2 (ALDH2) and heme oxygenase (HO)-1 at the protein level. In this article, the research progresses on cold ischemia injury of steatotic donor livers and relevant intervention measures were reviewed.

Distribution of genetic polymorphism of aldehyde dehydrogenase-2 (ALDH2) in Indonesian subjects.

Aldehyde dehydrogenase (ALDH) plays a pivotal role in the alcohol metabolism. Decreased activity of ALDH enzyme has more influence on the hypersensitivity to alcohol than of alcohol dehydrogenase. ALDH enzyme exists in several isozymes. Among these isozymes, ALDH2 is a major isozyme that has a very high affinity for acetaldehyde. Recent studies suggested that the deficiency of ALDH2 may be inherited. Functional polymorphism of ALDH2 gene has been observed in a nucleotide of the 487th codon. In the atypical gene, this codon consists of AAA nucleotides for lysine, instead of GAA for glutamic acid in the wild type gene. In this study, we have analyzed the genetic polymorphism of ALDH2 gene among 100 Indonesian students using genomic DNA extracted from hair roots. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods were performed for this purpose. Three oligonucleotide primers were designed for two steps PCR. The reverse primer R was intentionally constructed not to be 100% complementary to the template strand, to generate a restriction site for Eco RI within the variable nucleotide in the PCR product of ALDH2 gene. This study indicates that 70 subjects (70%) have wild type, 29 (29%) atypical heterozygote and only 1 (1%) atypical homozygote ALDH2 alleles. Conclusively, the atypical ALDH2 allele frequency in Indonesians (31/200) is higher than in Caucasoids (only about 5-10%), but less than in Mongoloids (40-50%). This may be due to the diverse ethnics of Indonesian population.

Effects of Genetic Factor, Life Styles, and Diet on Urinary Hippuric Acid Excretion in Toluene Exposed Workers / 대한산업의학회지

OBJECTIVES: The purpose was to investigate the distributions and the effects of genetic polymorphism of aldehyde dehydrogenase 2(ALDH2), cytochrome P450 1A1(CYP1A1), and cytochrome P450 2E1(CYP2E1) on the toluene metabolism. METHODS: The subjects consisted of 160 workers who were exposed to toluene in different industries such as paint manufacturing, painting on steel and wood products, printing, bonding, and coating. The exposed toluene level was monitored by passive air sampler, and the questionnaire variables were age, sex, smoking, drinking, previous nights drinking, use of personal protective equipment, work duration, and taking benzoic acid containing food. The urinary hippurric acid collected in the end of shift was corrected by urinary creatinine concentration. The genotypes of ALDH2, CYP1A1, and CYP2E1 were investigated using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) methods with DNA extracted from venous blood. RESULTS: The geometric mean and the geometric standard deviation of urinary hippuric acid concentration were 0. 44 g/g creatinine and 2. 80. The urinary hippuric acid concentration was significantly related to personal exposed toluene level among personal exposed toluene level, use of personal protective equipment, and benzoic acid containing food diet. The slope differences of the regression for ALDH2, CYP1A1, and CYP2El genetic polymorphism, age, smoking, and work duration tended to be significant. In multiple regression analysis, the regression coefficient of toluene, ALDH2, CYP1A1, CYP2E1 genetic polymorphism were significant. CONCLUSIONS: Prom the above results, urinary hippuric acid level after toluene exposure was significantly affected by the genetic polymorphism of ALDH2, CYP1A1, CYP2E1. It is needed further investigation of the urinary hippuric acid level considering the effect of genetic polymorphism.

Effect of Aldehyde dehydrogenase2 (ALDH2) Genotypes in Urinary Hippuric Acid Excretion as a Biological Exposure Index of Toluene / 대한산업의학회지

We investigated toluene exposure level, urinary hippuric acid concentrations, subjective symptoms and genotype of ALDH2 DNA in 134 exposed workers and 53 nonexposed workers for evaluating the effect of ALDH2 polymorphism on toluene metabolism and urinary hippuric acid concentration as biological exposure indices (BEI) of toluene. The results were as follows; 1. The percentage of inactive genotype of ALDH2 in exposed workers was lower than that of exposed (P=0.081). 2. The percentages of exposed workers with inactive genotype did not have any significant difference by the increase of toluene exposure level or work duration. 3. The frequency of drinking, monthly and maximum amount of alcohol intake in workers with normal genotype were significantly higher than those with inactive genotype. 4. The urinary hippuric acid concentration of nonexposed workers ,with inactive genotype was significantly lower than that with normal genotype. Under 100 ppm of toluene, similar but statistically insignificant trends were found, while above that concentration of toluene, reverse but statistically insignificant trends were found. 5. The number of acute and chronic subjective symptoms were increased positively with the concentration of toluene in workers with normal genotype, but ho such trends were found in workers with inactive genotype. 6. The result of simple linear regression between toluene and urinary hippuric acid concentrations showed a very significant positive linear relation-ship. The mean hippuric acid concentration of nonoccupational exposure was 0.289+/-0.227 (0.062-0.516) g/l. Toluene exposure level unable to discriminate with nonoccupational exposure estimated from regression equation, it range from 7.29 to 9.87 ppm. Considering above all things, it was useful to estimate the exposure level of toluene by means of analysing urinary hippuric acid concentration in both genotype workers, but the biological exposure indices (BEI) of both genotypes were different from each other. The BEI of the total exposed workers was 2.76 g/ I, which was lower than current criteria 3.0g/ I (2.5 g/g Cr), and it also suggest that the BEI for the exposed workers in our country be lowered to the appropriate level after further study.