含有甘油及氯化鈉的食品，經過酸水解或高溫加工產生食品汙染物三單氯丙二醇酯(3-monochloro-1,2-propanediol esters, 3-MCPDE)及二單氯丙二醇酯(2-monochloro-1,2-propanediol esters, 2-MCPDE)，經由攝食進入腸胃道再被水解成游離態的3-MCPD及2-MCPD。動物實驗研究顯示3-MCPD會損害腎臟及雄性生殖系統，然而3-MCPD造成毒性之機制並不清楚，並且2-MCPD毒性目前尚未證實。本研究探討3-MCPD及2-MCPD的毒性影響，並利用MIOX-NanoLuc基因轉殖小鼠觀察停止暴露汙染物後，腎臟損傷回復之可能性。大鼠腎臟近曲小管上皮細胞NRK-52E將用以探討3-MCPD是否藉由粒線體功能喪失，啟動粒線體自體吞噬作用(mitophagy)來誘導腎毒性。
28天亞急毒性動物實驗管餵給予雄性C57BL/6小鼠3-MCPD (1、2.5、5、10、25 mg/kg)和2-MCPD(1、5、10、25、50 mg/kg )，取其血清、尿液檢測腎肝功能生化值，並以H&E染色觀察腦、心、肺、腎、睪丸等器官受損情形。依據上述實驗結果選擇回復性試驗之3-MCPD暴露劑量(5、10、25 mg/kg)，馬兜鈴酸一型(aristolochic acid I)作為正向對照組。MIOX-NanoLuc基因轉殖小鼠暴露3-MCPD 28天後再停止管餵28天進行犧牲。每周收集尿液測定生化值變化，利用H&E染色觀察肺、腎組織回復情形。細胞實驗方面，暴露10 mΜ 3-MCPD後檢測粒線體膜電位、外膜動態蛋白及活性氧物質(reactive oxygen species, ROS)程度以判斷粒線體損傷情形，利用西方墨點法、免疫螢光染色等實驗分析粒線體自體吞噬作用機制。
實驗結果顯示，暴露3-MCPD的小鼠，僅血清中尿酸濃度相較控制組顯著增加。腎臟組織出現腎小管變性及免疫細胞浸潤，嚴重程度隨劑量增加而提高。25 mg/kg 3-MCPD處理後，肺臟發現肺泡腫脹、免疫細胞浸潤情況。然而2-MCPD僅在高劑量組(50 mg/kg)造成腎臟和心臟些微受損，統計結果無顯著差異，肝、腎功能生化值也無劑量效應。由此可推論3-MCPD毒性較2-MCPD高，並且兩者皆會誘導腎臟損傷。回復性試驗結果觀察到最高劑量(25 mg/kg)損傷指標冷光蛋白在第三週表達下降，停止暴露3-MCPD後回升。組織方面，實驗組與28天結果相比，腎臟受損情形降低，具有部分回復效果，肺臟則無受損。細胞結果發現暴露10 mΜ 3-MCPD後粒線體膜動態蛋白DRP1及MFN1表達失衡、ROS增加、粒線體膜電位下降且粒線體自體吞噬作用相關蛋白表達增加，螢光標記出現共定位區域，利用電子顯微鏡也觀察到暴露3-MCPD的組別出現粒線體自體吞噬作用型態。在加入DRP1抑制劑後NRK-52E細胞存活率上升，且粒腺體自體吞噬作用相關蛋白質表達皆下降。利用致弱DRP1基因之細胞顯示共同暴露3-MCPD後細胞凋亡情形降低，表示3-MCPD所誘導之粒線體自體吞噬作用對細胞是毒性機制。
總體而言，本研究發現3-MCPD毒性較2-MCPD劇烈，且兩物質皆會導致腎臟損傷。3-MCPD可能藉由粒線體功能喪失促使粒線體自體吞噬作用產生並誘導腎臟損傷。若停止暴露3-MCPD則腎臟損傷具有部分回復效果。

Food contaminants 3-monochloro-1,2-propanediol (3-MCPD) and 2- monochloro-1,3-propanediol (2-MCPD) are produced by high temperature in oil processing. Animals studies have demonstrated that 3-MCPD caused kidney and male reproduction system injury. Mechanistical studies indicated that 3-MCPD can reduce the mitochondrial membrane potential (MMP) and induced apoptosis. However, the toxicity of 2-MCPD has not been confirmed and exact mechanisms of 3-MCPD in nephrotoxicity is still unclear. The aim of this study is to investigate the toxicity effects of 3-MCPD and 2-MCPD, and MIOX mice were used to observe the reversibility of renal damage. We also investigate the mechanisms of 3-MCPD-induced renal toxicity via mitochondrial dysfunction leading to mitophagy pathway by NRK-52E cells. The results showed the kidney damage was increases dose-dependently, as shown by obvious tubule degeneration and infiltration in the kidney in mice after treated by 3-MCPD. Obvious pulmonary edema and infiltration were observed in lungs after high dose treatment. Contrary, there was minor kidney and heart injury in 2-MCPD high-dose treatment group. This suggested that, 3-MCPD is more toxic than 2-MCPD, and the kidney is the most sensitive organ to both. In the recovery study, the renal damage in 3-MCPD treated groups are less severe compared to the 28-day toxicity study, which indicated partial recovery of renal toxicity was observed. The results of in vitro studies showed that mitochondrial membrane dynamic protein expression imbalanced, ROS increased significantly and MMP decreased after 3-MCPD exposure. Mitophagy-related proteins were also increased and we observed mitophagy morphology in NRK-52E cells after 3-MCPD treatment. The proteins were decreased after cotreated with DRP1 inhibitor, Mdivi-1, and 3-MCPD. And the apoptosis level was decreased after 3-MCPD treatment in knockdown DRP1 NRK-52E cells. Overall, we suggested that 3-MCPD may induce renal damage via mitochondrial dysfunction and mitophagy, whereas ceasing exposure to 3-MCPD would lead to partial reversed in renal toxicity.

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