跳到主要內容

臺灣博碩士論文加值系統

(3.231.230.177) 您好!臺灣時間:2021/08/04 05:08
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

我願授權國圖
: 
twitterline
研究生:陳建翰
研究生(外文):Chien-Han Chen
論文名稱:機車廢氣對大鼠心臟及生殖發育毒性之探討
論文名稱(外文):Effects of Motorcycle Exhaust on Heart and Reproductive Development Toxicity in Rats
指導教授:翁祖輝翁祖輝引用關係
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:毒理學研究所
學門:醫藥衛生學門
學類:其他醫藥衛生學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
語文別:中文
論文頁數:98
中文關鍵詞:機車廢氣心臟毒性氧化壓力心臟超音波生殖發育毒性動情週期早期死胎率
外文關鍵詞:motrocycle exhaustcardiactoxicityoxidative stressendocardiographyreproductive development toxicityestrus cyclicityfetal death
相關次數:
  • 被引用被引用:1
  • 點閱點閱:172
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
暴露於品質不良的空氣、心臟疾病的好發,及男性精液品質的惡化,可能具有密切的關係。台灣都會區以機車廢氣 (motorcycle exhaust,ME) 為主要空氣汙染源。本文模擬人類可能暴露環境條件下,雌性大鼠暴露二行程機車廢氣二週,心臟重量對體重的相對重量有顯著上升,暴露 ME 組大鼠心臟的脂質過氧化現象也較控制組明顯上升,組織穀胱甘肽含量含量下降,cytochrome P450 的7-ethoxycoumarin O-dealkylase 活性下降,抗氧化酵素過氧化氫酶 (catalase,CAT) 活性下降,而雄性大鼠在相同條件暴露四週下,各生化指標亦有類似的變化趨勢,且抗氧化酵素穀胱甘肽轉移酶 (glutathione S-transferase,GST)、超氧化歧化酶 (superoxide dismutase,SOD) 及穀胱甘肽過氧化酶 (glutathione peroxidase,GPX), 活性皆下降,表示心臟的抗氧化系統失效可能為導致氧化性傷害之一種機制。雄性大鼠在暴露八週後,心臟病理切片之結果顯示心臟左、右心室尺寸增大、心臟隔膜的心肌細胞輕微纖維化,且右心室部位有單核細胞浸潤,左心室肌纖維有輕微腫大與肌纖維間隙寬度擴大的現象。心臟超音波數據顯示,心臟瓣膜及左心室後壁厚度增厚,而左心室空腔體積明顯下降,左心室心肌肥厚等現象。雄性大鼠在相同條件下,暴露四行程機車廢氣每天分別各為二、四、六小時,發現每日暴露四、六小時組別的大鼠心臟相對重量顯著上升,但心臟的各生化指標則皆無明顯變化。
  將懷孕第 7 天 (gestational day 7,GD 7) 之母鼠,呼吸暴露二行程機車廢氣持續至懷孕第 20 天 (GD 20),懷孕母鼠於 GD 20 及 GD 21 的體重,及此其間體重增加的幅度皆顯著低於控制組與自由組。暴露組母鼠的生產子代數目 / 著床點比率亦有低於控制組和自由組的趨勢,顯示暴露組中有較多的母鼠發生早期死胎的情況。觀察暴露組子代雄、雌性仔鼠在發育過程中,體重皆有明顯低於控制組與自由組的趨勢,且 anogential distance (AGD) / 體重比率、anovaginal distance (AVD) / 體重比率及vaginal-genital distance (VGD) / 體重比率具有上升的趨勢,推測暴露組母鼠泌乳的成分,可能具有來自廢氣中的毒性物質,而導致子代仔鼠發育情形較差,且在生殖發育的過程中,因雄激素的分佈受到干擾,產生雄性化的趨勢。
  雄性大鼠連續暴露二行程機車廢氣八週後,與雌性大鼠進行交配,觀察子代雄、雄性仔鼠的生殖發育情形。子代仔鼠於青春前期時,暴露組的存活率低於控制組,但不具統計意義上的顯著差異;暴露組雄性仔鼠於出生第 1 天 (postnatal day 1,PND 1) 及雌性仔鼠在 PND 14 時,肛門-生殖點距離 AGD / 體重比率均明顯低於控制組,且雌性仔鼠陰道開口的時間明顯提早。每日觀察雌性仔鼠動情週期,結果顯示,暴露組的週期規律性較差,正常的週期次數亦較少。雄、雌性仔鼠分別於 PND 56、98 與 140 時犧牲,雄性仔鼠在 PND 56 的前列腺、提肛與球海綿體肌 (LABC) 與尿道球腺,及 PND 98 時副睪與 LABC 相對重量明顯上升;暴露組雌性仔鼠於 PND 56 時卵巢相對重量有明顯上升,而在 PND 140 肝臟相對重量則顯著下降。子代雄性仔鼠睪丸的脂質過氧化、穀胱甘肽含量,以及睪丸與副睪尾的精子密度則皆沒有明顯差異。另外,探討雄、雌性子代仔鼠肝臟的生化指標的結果顯示,三個時間點暴露組雄性仔鼠的穀胱甘肽 glutathione 含量皆有下降的趨勢,其中以 PND 56 與 140 具有統計意義的顯著差異,雌性仔鼠亦皆有略低於控制組的趨勢,但皆無顯著差異。脂質過氧化方面,未加入亞鐵離子的情形下,暴露組雄性仔鼠的 molondialdehyde 值皆有下降趨勢,其中 PND56 與 140 具有顯著差異,而加入亞鐵離子後,暴露組於 PND 140 亦明顯下降;雌性仔鼠則僅在加入亞鐵離子的情形下,暴露組分別於 PND 56 及 98 有顯著下降。肝臟單氧酶方面,在 PND 98 時,暴露組雄性仔鼠aniline hydroxylase 活性有明顯下降的情形,雌性仔鼠 erythromycin N-demethylase 活性亦具有顯著的下降。探討雄性與雌性仔鼠的抗氧化酵素 GST、SOD、CAT、GPX 等活性,結果皆無明顯差異。
  本研究首次證明機車排放廢氣對大鼠心臟生化與功能指標的不良影響、子代雄性與雌性仔鼠生殖發育之干擾,以及對懷孕母鼠早期死胎率、子代生殖發育的負面影響。此結果將有助於我們對機車廢氣的危害評估。
The cardiac diseases and poor quality of semen are possibly associated with air pollution. Motorcycle exhaust (ME) is a major source of air pollution in the urban areas in Taiwan. The present studies showed that inhalation exposure of adult male rats to 2-stroke ME at environmental realistic conditions for 4 weeks increased heart relative weight and lipid peroxidation level, and decreased glutathione content, and the activities of 7-ethoxycoumarin O-dealkylase, glutathione S-transferase, superoxide dismutase, and glutathione peroxidase enzyme acitivities in heart. Similar effects were observed in female rats under same experimental conditions during 2 weeks exposure. The 2-stroke ME induced-cardiac oxidative damage is probably due to antioxidant defense failure. The histophathological study revealed that inhalation exposure to 2-stroke ME inhalation exposure for 8 weeks caused a slight larger size in the left and right ventricle of rat heart compared to control. Hearts showed focal minimal to slight myofibrosis in the septa, mononuclear cell infiltration in the right ventricle, and slight swelling myofibers and widening interspace between myofibers of left ventricle in ME group. The results of echocardiography analysis showed that 2-stroke ME increased the septa and left ventricle posterior wall thickness and LV mass and decreased the dimension of left ventricle cavity significantly. Under similar experimental conditions using a 4-stroke motorcycle engine of 2, 4, and 6 hours daily exposure for 4 weeks respectively, the heart relative weight were increased markedly in 4-hour and 6-hour daily exposure groups. There were no significant changes of cardiac effects in these ME groups.

Inhalation exposure of pregnant rats to 2-stroke ME from gestational (GD) 7 to GD 20, the body weights of ME group at GD 20 and 21 were lower than the body weights of control and free groups significantly. ME also decreased the number of offspring/number of implantation site ratio. The results showed that ME caused more fetal deaths in early periods. We have observed adverse effects of ME on reproductive development of offspring. The body weight of offspring was lower than control and free groups for the duration of development. Furthermore, the anogential distance (AGD)/body weight, anovaginal distance (AVD)/body weight and vaginal-genital distance (VGD)/body weight ratio of ME group female offspring were altered significantly. The results revealed that the ME exposure of pregnant female rats inhibited the general growth and disturbed the reproductive development of offspring.
  Adult male rats were exposed to 2-stroke ME for 8 weeks and subsequently mated with untreated female rats and the reproductive development of offspring was studied. The viability of ME group offspring showed a trend toward decrease. The AGD/body weight ratio of male and female offspring at postnatal day (PND) 1 and PND 14, respectively, were lower than control markedly. The vaginal opening day of ME group female rats was advanced significantly. The pattern of estrous cyclicity showed that the ME group female offspring had more disordered regularity. Furthermore, the number of normal cyclicity and number of normal cyclicity/rat ratio of ME group female offspring were lower than control. The male and female offspring were sacrificed at PND 56, 98, and 140 respectively. The prostate, levatro ani bulbocavernosus (LABC) and bulbourethral glands relative weights at PND 56, and epididymis and LABC relative weights at PND 98 of ME group male offspring were increased significantly. The ovary relative weight at PND 56 was increased, and liver relative weight at PND 140 of ME group female offspring was decreased markedly. Lipid peroxidation level, glutathione content, and sperm density were not altered in male offspring testis. On other experiments, we have investigated the biochemical marker changes in offspring liver. The result showed that glutathione contents were decreased in ME group male offspring liver at PND 56 and 140. Lipid peroxidation level in ME male offspring liver was lower than control at PND 56 and 98. Lipid peroxidation analysed by thiobarbituric acid-reactive substances formation with ferrous iron showed that the level of ME group female offspring in liver was lower than control at PND 140. With respective to monooxygenase activities, aniline hydroxylase activity of male offspring and erythromycin N-demethylase activity in female offspring liver were decreased significantly. Antioxidant enzyme activities were not changed.

  To the best of our knowledge, this is the first to show adverse effects of exposure to ME on biochemical markers and function of heart, reproductive development of offspring, and fetal viability. These results may assist in assessing the health risk associated with ME exposure.
目 錄
中文摘要…………………...…………………………………………………….............1
英文摘要…………………………………………………………………………............4
第一章 前言
第一節、日趨嚴重的空氣汙染議題…………………………….…………………..7
第二節、空氣汙染導致的健康危害及其機制……………….……………………..7
第三節、目前台灣機動車使用情況及機車廢氣組成分…………….…………......8
第四節、空氣汙染與心臟疾病之間的關聯…………………………………….....10
第五節、空氣汙染與精液品質惡化以及不孕之間的關聯…………………….....10
第六節、本篇研究目的………………………………………………………….....11
第二章 研究方法與步驟
第一節、呼吸暴露實驗
Ⅰ. 實驗動物……………………………………………………………………13
Ⅱ. 機車廢氣暴露裝置系統…………………………………………………....13
Ⅲ. 大鼠呼吸暴露機車廢氣實驗……………………………………………....14
Ⅳ. 懷孕母鼠呼吸暴露機車廢氣實驗………………………………………....14
第二節、 精子毒性評估
Ⅰ. 睪丸及副睪精子密度計算…………..……………………………………..14
第三節、 呼吸二行程機車廢氣大鼠之懷孕率實驗……...……….………………….15
第四節、 子代仔鼠發育觀察……………..…………………………………………...15
第五節、 酵素實驗測試
Ⅰ. 細胞微粒體及細胞質之製備……………………………………………....16
Ⅱ. 蛋白濃度測定……………………………………………………………....16
Ⅲ. 單氧酶活性測試
a. 7-Ethoxycoumarin O-Dealkylase Activity Assay………………………….....17
b. 7-Ethoxyresorufin O-Deethylase Activity Assay……………….………….......17
c. Methoxyresorufin O-Demethylase Activity Assay…………....……………….17
d. Pentoxyresorufin O-Dealkylase Activity Assay……………………………….17
e. Erythromycin N-Demethylase Activity Assay………………...………………18
f. Aniline Hydroxylase Activity Assay…………………………...……………...18
Ⅳ. 抗氧化酵素活性測試
a. Glutathione S-Transferase Activity Assay…………………………………….18
b. Superoxide Dismutase Activity Assay…………………………………….......18
c. Catalase Activity Assay…………………………………………………….....19
d. Total Glutathione Content Assay……...………………………………….......19
第六節、 脂質過氧化分析……………...…………………………………………….19
第七節、 血清酵素分析
Ⅰ. 肝臟細胞損傷指標
a. Alanine Aminotransferase Activity Assay………………………………….....19
b. Aspartate Aminotransferase Activity Assay………………...……………..20
Ⅱ. 心肌細胞損傷指標
a. Lactate Dehydrogenase Activity Assay………………………………….....20
b. Creatine Phosphokinase Activity Assay………………………………………20
第八節、 大鼠心臟功能測定
Ⅰ. 心電圖測定…………………………………………………………………..21
Ⅱ. 心臟超音波測定…………………………………………………………......22
第九節、 數據統計分析………….………………………………………………….22
第三章 結果
第一節、 二行程機車廢氣對雄性及雌性大鼠器官相對重量之影響………….....23
第二節、 暴露二行程機車廢氣之雄性大鼠心臟超音波及心電圖變化之影
響…………………………..…………………………………………….......23
第三節、 暴露二行程機車廢氣之雄性大鼠心臟組織病理變化之影響…………….24
第四節、 二行程機車廢氣對雄性及雌性大鼠血清肝臟細胞及心肌細胞急性
損傷生物指標之影響…….…………………………………………...........25
第五節、 二行程機車廢氣對雄性及雌性大鼠心臟穀胱甘肽含量和脂質過氧化
之影響…………………….…………………………………………...........25
第六節、 二行程機車廢氣對雄性及雌性大鼠心臟單氧酶活性與抗氧化酵素活
性之影響…………...……...…………………………………………...........26
第七節、 四行程機車廢氣對雄性大鼠體重、心臟相對重量及各項生化指標
之影響…………………….……………………………...............................26
第八節、 懷孕母鼠暴露二行程機車廢氣期間體重變化與早期死胎率之影
響..………………………...…………………………………………….......27
第九節、 暴露二行程機車廢氣之懷孕母鼠對子代仔鼠體重、AGD/體重比率、
AVD/體重比率及 VGD/體重比率與動情週期規律性之影響…...............28
第十節、 二行程機車廢氣對雄性大鼠精子密度變化之影響……....………..…….29
第十一節、 二行程機車廢氣對雄性大鼠生殖能力之影響…….……………..….….29
第十二節、 暴露二行程機車廢氣之親代雄性大鼠對子代仔鼠青春前期的存活
率、體重與 AGD/體重比率之影響………….………………...……….29
第十三節、 暴露二行程機車廢氣之親代雄性大鼠對子代雄性仔鼠陰莖包皮
分離、雌性仔鼠陰道開口與初次動情時間之影響………..…......…….30
第十四節、 暴露二行程機車廢氣之親代雄性大鼠對子代仔鼠青春期及成年
期生殖發育指標之影響………………………………………...…….....30
第十五節、 暴露二行程機車廢氣之親代雄性大鼠對子代雄性仔鼠睪丸精子
密度、穀胱甘肽含量與脂質過氧化之影響…………............................31
第十六節、 暴露二行程機車廢氣之親代雄性大鼠對子代雌性仔鼠動情週期
規律之影響……...………………………………………………………32
第十七節、 暴露二行程機車廢氣之親代雄性大鼠對子代雌、雄性仔鼠肝臟
穀胱甘肽含量、脂質過氧化、單氧酶活性與抗氧化酵素活性之
影響…………………………………...………………………………...33

第四章 討論
第一節、 二行程機車廢氣影響心臟生化指標及造成心肌肥厚的可能機制…….35
第二節、 暴露二行程機車廢氣懷孕母鼠與早期死胎、子代仔鼠生長不良
及生殖發育情形影響之關聯……………………….…….……………...39
第三節、 親代雄性大鼠暴露二行程機車廢氣影響子代仔鼠生殖發育的可
能機制……….…………………………………………..….…………….41
第四節、 親代雄性大鼠暴露二行程機車廢氣影響子代仔鼠肝臟單氧酶活
性與性賀爾蒙的關聯……….……………………………….…………...43
第五節、 結論……………………………………………………………………….45

參考文獻………………………………………………………………………………….46











表目錄
Table 1. Effects of 2-stroke ME inhalation exposure on relative organ weights
in male rats……………………………………...………………………………..56
Table 2. Effects of 2-stroke ME inhalation exposure on relative organ weights
in female rats………………...………………...…………………………………57
Table 3. Effect of treatment with 2-stroke ME inhalation exposure on
echocardiography in male rats………………...…………………………………58
Table 4. Effect of treatment with 2-stroke ME inhalation exposure on electrocardiography
in male rats…………………………………...…………......................................59
Table 5. Effects of treatment with 2-stroke ME inhalation exposure on aspartate
aminotransferase and alanine aminotransferase enzyme activities in male rat
serum………………………………………...…………………………………...60
Table 6. Effects of treatment with 2-stroke ME inhalation exposure on lactate
dehydrogenase and creatine kinase enzyme activities in male and female rat
sera…………………………………………...…………………………………..61
Table 7. Effects of treatment with 2-stroke ME inhalation exposure on total
glutathione content and lipid peroxidation in male and female rat hearts...……..62
Table 8. Effects of treatment with 2-stroke ME inhalation exposure on
monooxygenase activities in male and female rat hearts………………...……..63
Table 9. Effects of treatment with 2-stroke ME inhalation exposure on antioxidant enzyme
activities in male and female rat hearts………………………………………….64
Table 10. Effects of treatment with 4-stroke ME inhalation exposure on body weights
and relative organ weights of heart in male rats……...………………………...65
Table 11. Effects of treatment with 4-stroke ME inhalation exposure on lipid
peroxidation, total GSH content, monooxygenase and antioxidant enzyme activities in male rat heart and cardiac cell damage markers
in male rat serum…..…………………………...…………….………………….66
Table 12. Effects of treatment of pregnant female rats with 2-stroke ME inhalation
exposure on body weight……………………………….……………………….67
Table 13. Effects of treatment of pregnant female rats with 2-stroke ME inhalation
exposure on number of offspring / number of implantation site ratio…....68
Table 14. Effect of in utero treatment with 2-stroke ME inhalation exposure on
body weight in male offspring….………….………………………………...69
Table 15. Effect of in utero treatment with 2-stroke ME inhalation exposure on
body weight in female offspringing………………………………………….....70
Table 16. Effects of in utero treatment with 2-stroke ME inhalation exposure on
estrus cyclicity regularity and he frequency of estrus cyclicity phases in
female offspring……………………………………………………………...…71
Table 17. Effect of 2-stroke ME inhalation exposure on sperm density in male rats…..….72
Table 18. Reproductive toxicity of male rats exposed to 2-stroke ME by inhalation……..73
Table 19. Effects of paternal treatment with 2-stroke ME inhalation exposure of
parental male and female rats on pre-puberty male offspring viability,
body weight, and AGD/body weight ratio………………………………….…..74
Table 20. Effects of paternal treatment with 2-stroke ME inhalation exposure on the age
of preputial separation in male offspring and age of vaginal opening and onset
of estrus cycle in female offspring….…...………………….………...........…...75
Table 21. Effects of paternal treatment with 2-stroke ME inhalation exposure of on
the pubertal and adult male offspring reproductive development…….…….…...76
Table 22. Effects of paternal treatment with 2-stroke ME inhalation exposure on the
pubertal and adult female offspring reproductive development……….…...…..77
Table 23. Effects of paternal treatment with 2-stroke ME inhalation exposure on
body weight and relative organ weight of the pubertal and adult male
offspring……..…………...……………………………………………………..78
Table 24. Effects of paternal treatment with 2-stroke ME inhalation exposure on
body weight and relative organ weight of the pubertal and adult female
offspring………………………………………………………………………..79
Table 25. Effects of paternal treatment with 2-stroke ME inhalation exposure on
sperm densities in male offspring testis and cauda epididymis…….………….80
Table 26. Effects of paternal treatment with 2-stroke ME inhalation exposure on
total glutathione content and lipid peroxidation in male offspring testis…….…81
Table 27. Effects of paternal treatment with 2-stroke ME inhalation exposure on
estrus cyclicity regularity in female offspring………………………………….82
Table 28. Effects of paternal treatment with 2-stroke ME inhalation exposure on
the frequency of estrus cyclicity phases in female offspring…………………...83
Table 29. Effects of paternal treatment with 2-stroke ME inhalation exposure on
total glutathione content and lipid peroxidation in male and female
offspring liver…………………………………………………………………..84
Table 30. Effects of paternal treatment with 2-stroke ME inhalation exposure on
monooxygenase activities in male and female rat livers……………………….85
Table 31. Effects of paternal treatment with 2-stroke ME inhalation exposure on
antioxidant enzyme activities in male and female offspring livers…………….86










圖目錄
Fig 1. Effect of treatment with 2-stroke ME inhalation exposure on echocardiography
in male rats………………...……………………………………………………...87
Fig 2. Effects of 2-stroke ME inhalation exposure on cardiac histopathological
changes in male rats……...……………………………………………………….88
Fig 3. Effects of 2-stroke ME inhalation exposure on cardiac histopathological
changes in male rats (continued)…………………………….…….89 (continued)
Fig 4. Effects of 2-stroke ME inhalation exposure on cardiac histopathological
changes in male rats (continued)……………….…………………….90 (continued)
Fig 5. Effects of 2-stroke ME inhalation exposure on cardiac histopathological
changes in male rats (continued)….…………….……………………91 (continued)
Fig 6. Effects of 2-stroke ME inhalation exposure on cardiac histopathological
changes in male rats (continued)……………….……………...……..92 (continued)
Fig 7. Effect of in utero treatment with 2-stroke ME inhalation exposure on
AGD/body ratio in male offspring……………….…….………………………….93
Fig 8. Effect of in utero treatment with 2-stroke ME inhalation exposure on
AGD/body ratio in female offspring…………………..…………………………..94
Fig 9. Effect of in utero treatment with 2-stroke ME inhalation exposure on
AVD/body ratio in female offspring…………..……………..……………………95
Fig 10. Effect of in utero treatment with 2-stroke ME inhalation exposure on
VGD/body ratio in female offspring…………..…….………………...…………...96
Fig 11. Effect of in utero treatment with 2-stroke ME inhalation exposure on estrus
cyclicity regularity in female offspring……………………………….……………97
Fig 12. Effect of paternal treatment with 2-stroke ME inhalation exposure on estrus
cyclicity regularity in female offspring (continued).…..………..….....98 (continued)
參考文獻
1.Adiga, I.K., and Nair, R.R. (2008). Multiple signaling pathways coordinately mediate reactive oxygen species dependent cardiomyocyte hypertrophy. Cell Biochem Funct 26, 346-351.
2.Alvares, A.P., and Mannering, G.J. (1970). Two-substrate kinetics of drug-metabolizing enzyme systems of hepatic microsomes. Mol Pharmacol 6, 206-212.
3.Boveris, A., Cadenas, E., Reiter, R., Filipkowski, M., Nakase, Y., and Chance, B. (1980). Organ chemiluminescence: noninvasive assay for oxidative radical reactions. Proc Natl Acad Sci U S A 77, 347-351.
4.Bowman, C.J., Barlow, N.J., Turner, K.J., Wallace, D.G., and Foster, P.M. (2003). Effects of in utero exposure to finasteride on androgen-dependent reproductive development in the male rat. Toxicol Sci 74, 393-406.
5.Brunekreef, B., and Holgate, S.T. (2002). Air pollution and health. Lancet 360, 1233-1242.
6.Burke, M.D., and Mayer, R.T. (1974). Ethoxyresorufin: direct fluorimetric assay of a microsomal O-dealkylation which is preferentially inducible by 3-methylcholanthrene. Drug Metab Dispos 2, 583-588.
7.Cadenas, E., and Sies, H. (1984). Low-level chemiluminescence as an indicator of singlet molecular oxygen in biological systems. Methods Enzymol 105, 221-231.
8.Carlsen, E., Giwercman, A., Keiding, N., and Skakkebaek, N.E. (1992). Evidence for decreasing quality of semen during past 50 years. BMJ 305, 609-613.
9.Cave, A., Grieve, D., Johar, S., Zhang, M., and Shah, A.M. (2005). NADPH oxidase-derived reactive oxygen species in cardiac pathophysiology. Philos Trans R Soc Lond B Biol Sci 360, 2327-2334.
10.Cesselli, D., Jakoniuk, I., Barlucchi, L., Beltrami, A.P., Hintze, T.H., Nadal-Ginard, B., Kajstura, J., Leri, A., and Anversa, P. (2001). Oxidative stress-mediated cardiac cell death is a major determinant of ventricular dysfunction and failure in dog dilated cardiomyopathy. Circ Res 89, 279-286.
11.Chadwick, R.W., Cooper, R.L., Chang, J., Rehnberg, G.L., and McElroy, W.K. (1988). Possible antiestrogenic activity of lindane in female rats. J Biochem Toxicol 3, 147-158.
12.Chang, C.C., Hwang, J.S., Chan, C.C., Wang, P.Y., Hu, T.H., and Cheng, T.J. (2005). Effects of concentrated ambient particles on heart rate variability in spontaneously hypertensive rats. J Occup Health 47, 471-480.
13.Chen, G.F., Ronis, M.J., Ingelman-Sundberg, M., and Badger, T.M. (1999). Hormonal regulation of microsomal cytochrome P4502E1 and P450 reductase in rat liver and kidney. Xenobiotica 29, 437-451.
14.Cheng, T.J., Hwang, J.S., Wang, P.Y., Tsai, C.F., Chen, C.Y., Lin, S.H., and Chan, C.C. (2003). Effects of concentrated ambient particles on heart rate and blood pressure in pulmonary hypertensive rats. Environ Health Perspect 111, 147-150.
15.Cihak, R., Gutmann, E., and Hanzlikova, V. (1970). Involution and hormone-induced persistence of the M. sphincter (levator) ani in female rats. J Anat 106, 93-110.
16.Clancy, L., Goodman, P., Sinclair, H., and Dockery, D.W. (2002). Effect of air-pollution control on death rates in Dublin, Ireland: an intervention study. Lancet 360, 1210-1214.
17.Davis, R.J. (1993). The mitogen-activated protein kinase signal transduction pathway. J Biol Chem 268, 14553-14556.
18.De Rosa, M., Zarrilli, S., Paesano, L., Carbone, U., Boggia, B., Petretta, M., Maisto, A., Cimmino, F., Puca, G., Colao, A., et al. (2003). Traffic pollutants affect fertility in men. Hum Reprod 18, 1055-1061.
19.Delbosc, S., Cristol, J.P., Descomps, B., Mimran, A., and Jover, B. (2002). Simvastatin prevents angiotensin II-induced cardiac alteration and oxidative stress. Hypertension 40, 142-147.
20.Furuta, C., Suzuki, A.K., Taneda, S., Kamata, K., Hayashi, H., Mori, Y., Li, C., Watanabe, G., and Taya, K. (2004). Estrogenic activities of nitrophenols in diesel exhaust particles. Biol Reprod 70, 1527-1533.
21.Ghosh, M.C., Wang, X., Li, S., and Klee, C. (2003). Regulation of calcineurin by oxidative stress. Methods Enzymol 366, 289-304.
22.Gonzalez-Jasso, E., Lopez, T., Lucas, D., Berthou, F., Manno, M., Ortega, A., and Albores, A. (2003). CYP2E1 regulation by benzene and other small organic chemicals in rat liver and peripheral lymphocytes. Toxicol Lett 144, 55-67.
23.Gray, L.E., Jr., Ostby, J., Ferrell, J., Rehnberg, G., Linder, R., Cooper, R., Goldman, J., Slott, V., and Laskey, J. (1989). A dose-response analysis of methoxychlor-induced alterations of reproductive development and function in the rat. Fundam Appl Toxicol 12, 92-108.
24.Gray, L.E., Jr., Ostby, J., Monosson, E., and Kelce, W.R. (1999). Environmental antiandrogens: low doses of the fungicide vinclozolin alter sexual differentiation of the male rat. Toxicol Ind Health 15, 48-64.
25.Gray, L.E., Jr., Ostby, J.S., and Kelce, W.R. (1994). Developmental effects of an environmental antiandrogen: the fungicide vinclozolin alters sex differentiation of the male rat. Toxicol Appl Pharmacol 129, 46-52.
26.Greenlee, W.F., and Poland, A. (1978). An improved assay of 7-ethoxycoumarin O-deethylase activity: induction of hepatic enzyme activity in C57BL/6J and DBA/2J mice by phenobarbital, 3-methylcholanthrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin. J Pharmacol Exp Ther 205, 596-605.
27.Griffith, O.W. (1980). Determination of glutathione and glutathione disulfide using glutathione reductase and 2-vinylpyridine. Anal Biochem 106, 207-212.
28.Guengerich, F.P., Martin, M.V., Beaune, P.H., Kremers, P., Wolff, T., and Waxman, D.J. (1986). Characterization of rat and human liver microsomal cytochrome P-450 forms involved in nifedipine oxidation, a prototype for genetic polymorphism in oxidative drug metabolism. J Biol Chem 261, 5051-5060.
29.Gupta, C., Shapiro, B.H., and Yaffe, S.J. (1980). Reproductive dysfunction in male rats following prenatal exposure to phenobarbital. Pediatr Pharmacol (New York) 1, 55-62.
30.Gurgueira, S.A., Lawrence, J., Coull, B., Murthy, G.G., and Gonzalez-Flecha, B. (2002). Rapid increases in the steady-state concentration of reactive oxygen species in the lungs and heart after particulate air pollution inhalation. Environ Health Perspect 110, 749-755.
31.Guthenberg, C., Alin, P., and Mannervik, B. (1985). Glutathione transferase from rat testis. Methods Enzymol 113, 507-510.
32.Gutmann, E., Hanzlikova, V., and Cihak, R. (1967). Persistence of the levator ani muscle in female rats. Experientia 23, 852-853.
33.Halliwell, B., and Gutteridge, J.M. (1990). Role of free radicals and catalytic metal ions in human disease: an overview. Methods Enzymol 186, 1-85.
34.Hanzlikova, V., Schiaffino, S., and Settembrini, P. (1970). Histochemical fiber types characteristics in the normal and the persistent levator ani muscle of the rat. Histochemie 22, 45-50.
35.Hayes, C.L., Spink, D.C., Spink, B.C., Cao, J.Q., Walker, N.J., and Sutter, T.R. (1996). 17 beta-estradiol hydroxylation catalyzed by human cytochrome P450 1B1. Proc Natl Acad Sci U S A 93, 9776-9781.
36.Hougaard, K.S., Jensen, K.A., Nordly, P., Taxvig, C., Vogel, U., Saber, A.T., and Wallin, H. (2008). Effects of prenatal exposure to diesel exhaust particles on postnatal development, behavior, genotoxicity and inflammation in mice. Part Fibre Toxicol 5, 3.
37.Izumiya, Y., Kim, S., Izumi, Y., Yoshida, K., Yoshiyama, M., Matsuzawa, A., Ichijo, H., and Iwao, H. (2003). Apoptosis signal-regulating kinase 1 plays a pivotal role in angiotensin II-induced cardiac hypertrophy and remodeling. Circ Res 93, 874-883.
38.Jensen, T.K., Carlsen, E., Jorgensen, N., Berthelsen, J.G., Keiding, N., Christensen, K., Petersen, J.H., Knudsen, L.B., and Skakkebaek, N.E. (2002). Poor semen quality may contribute to recent decline in fertility rates. Hum Reprod 17, 1437-1440.
39.Kamataki, T., Kitada, M., Chiba, K., Kitagawa, H., Imai, Y., and Sato, R. (1980). Enhancement by cyanide of aniline p-hydroxylation activity in rat liver microsomes. Biochem Pharmacol 29, 1141-1147.
40.Kawashima, K., Nakaura, S., Nagao, S., Tanaka, S., and Kuwamura, T. (1975). Quantitative evaluation of virilizing activity of steroids by measuring morphological changes in uro-genital region of rats. Endocrinol Jpn 22, 439-444.
41.Kodavanti, U.P., Moyer, C.F., Ledbetter, A.D., Schladweiler, M.C., Costa, D.L., Hauser, R., Christiani, D.C., and Nyska, A. (2003). Inhaled environmental combustion particles cause myocardial injury in the Wistar Kyoto rat. Toxicol Sci 71, 237-245.
42.Kuo, M.L., Jee, S.H., Chou, M.H., and Ueng, T.H. (1998). Involvement of oxidative stress in motorcycle exhaust particle-induced DNA damage and inhibition of intercellular communication. Mutat Res 413, 143-150.
43.Kwon, S.H., Pimentel, D.R., Remondino, A., Sawyer, D.B., and Colucci, W.S. (2003). H(2)O(2) regulates cardiac myocyte phenotype via concentration-dependent activation of distinct kinase pathways. J Mol Cell Cardiol 35, 615-621.
44.Laws, S.C., Carey, S.A., Ferrell, J.M., Bodman, G.J., and Cooper, R.L. (2000). Estrogenic activity of octylphenol, nonylphenol, bisphenol A and methoxychlor in rats. Toxicol Sci 54, 154-167.
45.Lee, C.C., Liao, J.W., and Kang, J.J. (2004). Motorcycle exhaust particles induce airway inflammation and airway hyperresponsiveness in BALB/C mice. Toxicol Sci 79, 326-334.
46.Lowry, O.H., Rosebrough, N.J., Farr, A.L., and Randall, R.J. (1951). Protein measurement with the Folin phenol reagent. J Biol Chem 193, 265-275.
47.Lubet, R.A., Mayer, R.T., Cameron, J.W., Nims, R.W., Burke, M.D., Wolff, T., and Guengerich, F.P. (1985). Dealkylation of pentoxyresorufin: a rapid and sensitive assay for measuring induction of cytochrome(s) P-450 by phenobarbital and other xenobiotics in the rat. Arch Biochem Biophys 238, 43-48.
48.Mahadevan, B., Parsons, H., Musafia, T., Sharma, A.K., Amin, S., Pereira, C., and Baird, W.M. (2004). Effect of artificial mixtures of environmental polycyclic aromatic hydrocarbons present in coal tar, urban dust, and diesel exhaust particulates on MCF-7 cells in culture. Environ Mol Mutagen 44, 99-107.
49.Misra, H.P., and Fridovich, I. (1972). The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 247, 3170-3175.
50.Mohallem, S.V., de Araujo Lobo, D.J., Pesquero, C.R., Assuncao, J.V., de Andre, P.A., Saldiva, P.H., and Dolhnikoff, M. (2005). Decreased fertility in mice exposed to environmental air pollution in the city of Sao Paulo. Environ Res 98, 196-202.
51.Molkentin, J.D., Lu, J.R., Antos, C.L., Markham, B., Richardson, J., Robbins, J., Grant, S.R., and Olson, E.N. (1998). A calcineurin-dependent transcriptional pathway for cardiac hypertrophy. Cell 93, 215-228.
52.Nakamura, K., Fushimi, K., Kouchi, H., Mihara, K., Miyazaki, M., Ohe, T., and Namba, M. (1998). Inhibitory effects of antioxidants on neonatal rat cardiac myocyte hypertrophy induced by tumor necrosis factor-alpha and angiotensin II. Circulation 98, 794-799.
53.Nash, T. (1953). The colorimetric estimation of formaldehyde by means of the Hantzsch reaction. Biochem J 55, 416-421.
54.Ohkawa, H., Ohishi, N., and Yagi, K. (1978). Reaction of linoleic acid hydroperoxide with thiobarbituric acid. J Lipid Res 19, 1053-1057.
55.Peters, A., Dockery, D.W., Muller, J.E., and Mittleman, M.A. (2001). Increased particulate air pollution and the triggering of myocardial infarction. Circulation 103, 2810-2815.
56.Peters, A., and Pope, C.A., 3rd (2002). Cardiopulmonary mortality and air pollution. Lancet 360, 1184-1185.
57.Pippenger, C.E., Browne, R.W., and Armstrong, D. (1998). Regulatory antioxidant enzymes. Methods Mol Biol 108, 299-313.
58.Rayment, N.B., Haven, A.J., Madden, B., Murday, A., Trickey, R., Shipley, M., Davies, M.J., and Katz, D.R. (1999). Myocyte loss in chronic heart failure. J Pathol 188, 213-219.
59.Rhees, R.W., Kirk, B.A., Sephton, S., and Lephart, E.D. (1997). Effects of prenatal testosterone on sexual behavior, reproductive morphology and LH secretion in the female rat. Dev Neurosci 19, 430-437.
60.Rockett, J.C., Narotsky, M.G., Thompson, K.E., Thillainadarajah, I., Blystone, C.R., Goetz, A.K., Ren, H., Best, D.S., Murrell, R.N., Nichols, H.P., et al. (2006). Effect of conazole fungicides on reproductive development in the female rat. Reprod Toxicol 22, 647-658.
61.Rosalki, S.B. (1967). An improved procedure for serum creatine phosphokinase determination. J Lab Clin Med 69, 696-705.
62.Sabri, A., Hughie, H.H., and Lucchesi, P.A. (2003). Regulation of hypertrophic and apoptotic signaling pathways by reactive oxygen species in cardiac myocytes. Antioxid Redox Signal 5, 731-740.
63.Saxon, A., and Diaz-Sanchez, D. (2005). Air pollution and allergy: you are what you breathe. Nat Immunol 6, 223-226.
64.Slama, R., Morgenstern, V., Cyrys, J., Zutavern, A., Herbarth, O., Wichmann, H.E., and Heinrich, J. (2007). Traffic-related atmospheric pollutants levels during pregnancy and offspring''s term birth weight: a study relying on a land-use regression exposure model. Environ Health Perspect 115, 1283-1292.
65.Sorhaug, S., Steinshamn, S., Nilsen, O.G., and Waldum, H.L. (2006). Chronic inhalation of carbon monoxide: effects on the respiratory and cardiovascular system at doses corresponding to tobacco smoking. Toxicology 228, 280-290.
66.Toshimori, K. (2003). Biology of spermatozoa maturation: an overview with an introduction to this issue. Microsc Res Tech 61, 1-6.
67.Tzeng, H.P., Yang, R.S., Ueng, T.H., Lin-Shiau, S.Y., and Liu, S.H. (2003). Motorcycle exhaust particulates enhance vasoconstriction in organ culture of rat aortas and involve reactive oxygen species. Toxicol Sci 75, 66-73.
68.Ueng, T.H., Hu, S.H., Chen, R.M., Wang, H.W., and Kuo, M.L. (2000). Induction of cytochrome P-450 1A1 in human hepatoma HepG2 and lung carcinoma NCI-H322 cells by motorcycle exhaust particulate. J Toxicol Environ Health A 60, 101-119.
69.Ueng, T.H., Hung, C.C., Kuo, M.L., Chan, P.K., Hu, S.H., Yang, P.C., and Chang, L.W. (2005). Induction of fibroblast growth factor-9 and interleukin-1alpha gene expression by motorcycle exhaust particulate extracts and benzo(a)pyrene in human lung adenocarcinoma cells. Toxicol Sci 87, 483-496.
70.Ueng, T.H., Wang, H.W., Huang, Y.P., and Hung, C.C. (2004a). Antiestrogenic effects of motorcycle exhaust particulate in MCF-7 human breast cancer cells and immature female rats. Arch Environ Contam Toxicol 46, 454-462.
71.Ueng, T.H., Wang, H.W., Hung, C.C., and Chang, H.L. (2004b). Effects of motorcycle exhaust inhalation exposure on cytochrome P-450 2B1, antioxidant enzymes, and lipid peroxidation in rat liver and lung. J Toxicol Environ Health A 67, 875-888.
72.Vernet, P., Aitken, R.J., and Drevet, J.R. (2004). Antioxidant strategies in the epididymis. Mol Cell Endocrinol 216, 31-39.
73.Watanabe, N. (2005). Decreased number of sperms and Sertoli cells in mature rats exposed to diesel exhaust as fetuses. Toxicol Lett 155, 51-58.
74.Watanabe, N., and Oonuki, Y. (1999). Inhalation of diesel engine exhaust affects spermatogenesis in growing male rats. Environ Health Perspect 107, 539-544.
75.Waxman, D.J., Attisano, C., Guengerich, F.P., and Lapenson, D.P. (1988). Human liver microsomal steroid metabolism: identification of the major microsomal steroid hormone 6 beta-hydroxylase cytochrome P-450 enzyme. Arch Biochem Biophys 263, 424-436.
76.Wilkins, B.J., Dai, Y.S., Bueno, O.F., Parsons, S.A., Xu, J., Plank, D.M., Jones, F., Kimball, T.R., and Molkentin, J.D. (2004). Calcineurin/NFAT coupling participates in pathological, but not physiological, cardiac hypertrophy. Circ Res 94, 110-118.
77.Williams, T.M., and Borghoff, S.J. (2000). Induction of testosterone biotransformation enzymes following oral administration of methyl tert-butyl ether to male Sprague-Dawley rats. Toxicol Sci 57, 147-155.
78.Wolf, C.J., Hotchkiss, A., Ostby, J.S., LeBlanc, G.A., and Gray, L.E., Jr. (2002). Effects of prenatal testosterone propionate on the sexual development of male and female rats: a dose-response study. Toxicol Sci 65, 71-86.
79.Wroblewski, F., and Ladue, J.S. (1955). Lactic dehydrogenase activity in blood. Proc Soc Exp Biol Med 90, 210-213.
80.Xiao, G.G., Wang, M., Li, N., Loo, J.A., and Nel, A.E. (2003). Use of proteomics to demonstrate a hierarchical oxidative stress response to diesel exhaust particle chemicals in a macrophage cell line. J Biol Chem 278, 50781-50790.
81.Yamaguchi, O., Higuchi, Y., Hirotani, S., Kashiwase, K., Nakayama, H., Hikoso, S., Takeda, T., Watanabe, T., Asahi, M., Taniike, M., et al. (2003). Targeted deletion of apoptosis signal-regulating kinase 1 attenuates left ventricular remodeling. Proc Natl Acad Sci U S A 100, 15883-15888.
82.Yandle, T.G., Richards, A.M., Gilbert, A., Fisher, S., Holmes, S., and Espiner, E.A. (1993). Assay of brain natriuretic peptide (BNP) in human plasma: evidence for high molecular weight BNP as a major plasma component in heart failure. J Clin Endocrinol Metab 76, 832-838.
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top