博士 / 國立陽明大學 / 環境與職業衛生研究所 / 107 / Acrolein, a highly reactive unsaturated aldehyde and respiratory irritant, is formed during combustion (e.g., cigarette smoke, exhaust gas), high-temperature cooking of foods, and in vivo as a by product of oxidative stress and polyamine metabolism. 3-Hydroxypropyl mercapturic acid (3-HPMA), the main metabolite of acrolein in urine, is formed by glutathione (GSH) conjugation following the reduction and normal metabolic processing to a mercapturic acid.
The study was designed to test the hypothesis that the alkaline oral environment (pH 8-11) included by chewing slake lime containing betel quid will facilitate the absorption of acrolein (pKa 9.6) exposed from smoking. On the other hand, the previous study has found that the concentration of endogenous acrolein-protein bond (PC-Acr) in cerebrospinal fluid and blood in patients with Alzheimer's disease in Taiwan will increase, but in urine. The 3-HPMA concentration results are not yet clear.
The aim of this study is to explore two points: (1) Whether acrolein in cigarettes will increase in the alkaline environment of chewing betel quid, resulting in an increase in the concentration of 3-HPMA in the urine and DNA-acrolein (Acr-dG) is increased in the epithelial cells of the buccal membrane. In addition, because nicotine in cigarettes is alkaline, it is also necessary to investigate whether the concentration of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) metabolite 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in the urine of smokers will follow increase via chewing betel quid. Urine samples of oral squamous cell carcinoma (OSCC) patients were obtained from Mackay Memorial Hospital Tamshui Branch and healthy subjects from Kaohsiung area. (2) To explore whether the 3-HPMA content in urine can be used as a reference substance of Alzheimer's disease (AD). Urine samples of AD patients were obtained from Taipei Veterans Hospital, and further analyzed with age, gender and the Mini-Mental State Examination (MMSE).
The results showed that in the 3-HPMA of urine, the mean concentration of cigarette-smoking (CS) with betel quid (BQ) chewing history (n=99) (9.1 ± 9.6 μmole /g creatinine) was significantly higher than CS (n=74) (5.6 ± 5.0 μmole /g creatinine) (p<0.01). The statistical results indicate that the concentration of 3-HPMA/creatinine in urine is significantly increased with the increase in smoking and chewing betel quid. Exogenous acrolein may increase the absorption of acrolein by the alkaline environment generated by chewing betel quid and increase the concentration of 3-HPMA in the urine. The statistical results indicate that the concentration of 3-HPMA/creatinine in urine is significantly increased with the increase in smoking and chewing betel quid behavior. Subsequently, it was further found that the smoking age of more than 15 years, the concentration of 3-HPMA in the urine of population who smoked with betel quid chewing was significantly higher than that of only smoking (p<0.01).
The total NNAL in the urine of the healthy group of CS (258.9 ± 204.1 pg/mg creatinine) was significantly higher than CS+BQ (n=99) (151.9 ± 118.9 pg/mg creatinine) (p < 0.001). The Free NNAL in the urine of the healthy group of CS (n=74) (67.7 ± 96.4 pg/mg creatinine) was significantly higher than CS+BQ (n=99) (30.3 ± 58.0 pg/mg creatinine) (p<0.01). This result may be related to safrole in betel quit could induce liver CYP2As enzyme, which increases the α-hydroxylation of NNK, resulting in a decrease in NNAL emissions.
This study was further found that in the urine 3-HPMA, CS+BQ (n=99) (9.1 ± 9.6 μmole/g creatinine) was significantly higher than oral cancer patients (oral squamous cell carcinoma, OSCC) (n=77) (0.7 ± 0.7 μmole/g creatinine) (p<0.001). In addition, the total NNAL in the urine of the healthy group of CS (n=74) (258.9 ± 204.1 pg/mg creatinine) was higher than OSCC (n=77) (215.3 ± 129.8 pg/mg creatinine), but there was no significant difference (p=0.246). However, the Free NNAL in the urine of the healthy group of CS (n=74) (67.7 ± 96.4 pg/mg creatinine) was significantly higher than OSCC (n=77) (20.7 ± 43.0 pg/mg creatinine) (p<0.01). The result may be due to the low concentration of GSH in OSCC patients, and the acrolein conjugate GSH are less.
In the Alzheimer's disease study, the results of the control group (2.2 ± 2.4 µmole/g creatinine) was 1.2 fold higher than Alzheimer's disease (1.8 ± 1.8 µmole/g creatinine) (p=0.264). According to the results, endogenous acrolein may decrease in the amount of GSH conjugated with acrolein in patients with Alzheimer's disease. On the other hand, 3-HPMA is associated with an increase in MMSE, and this study is inferred to be related to the severity of the disease.
| Identifer | oai:union.ndltd.org:TW/107YM005515004 |
| Date | January 2019 |
| Creators | Han-Hsing Tsou, 鄒瀚興 |
| Contributors | Tsung-Yun Liu, Cheng-Chang Yang, 劉宗榮, 楊振昌 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 140 |
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