The current study aimed to investigate the hepatotoxicity of rats administered with chronic low-dose acrylamide (AA) by using metabonomics technology on the basis of ultraperformance liquid chromatography–mass spectrometry (UPLC-MS). A total of 40 male Wistar rats were randomly divided into the following four groups: control, low-dose AA (0.2 mg/kg bw, non-carcinogenic end-point based on the induction of morphological nerve changes in rats), middle-dose AA (1 mg/kg bw), and high-dose AA (5 mg/kg bw). The rats continuously received AA by administering it in drinking water daily for 16 weeks. After the treatment, rat livers were collected for metabonomics analysis and histopathology examination. Principal components analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) were used to investigate the metabonomics profile changes in rat liver tissues and screen the potential biomarkers.

Fourteen metabolites were identified with significant changes in intensities (increased or decreased compared with the control group) as a result of treatment (p < 0.05 or p < 0.01). These metabolites included tauro-b-muricholic acid, docosapentaenoic acid, sphingosine 1-phosphate, taurodeoxycholic acid, lysoPE(20:5), cervonyl carnitine, linoleyl carnitine, docosahexaenoic acid, lysoPC(20:4), lysoPE(18:3), PA(20:4), stearidonyl carnitine, alpha-linolenic acid, and lysoPA(18:0).

Results showed that chronic exposure to AA at NOAEL (0.2 mg/kg bw) exhibited no toxic effect in rat livers at the metabolic level. AA induced oxidative stress to the liver and disrupted lipid metabolism. The results of liver histopathology examination further supported the metabonomic results.

目前的研究旨在通过基于超高效液相色谱-质谱（UPLC-MS）的代谢组学技术，研究慢性低剂量丙烯酰胺（AA）所致大鼠的肝毒性。将40只雄性Wistar大鼠随机分为以下四组：对照组，低剂量AA（0.2 mg / kg体重，基于诱导大鼠形态神经变化的非致癌终点），中剂量AA（1 mg / kg bw）和高剂量AA（5 mg / kg bw）。通过每天在饮用水中给予AA连续16周，大鼠连续接受AA。治疗后，收集大鼠肝脏进行代谢组学分析和组织病理学检查。

经治疗后，鉴定出十四种代谢物的强度发生了显着变化（与对照组相比有所增加或减少）（p  <0.05或p  <0.01）。这些代谢物包括牛磺酸b-甲酚酸，二十二碳五烯酸，鞘氨醇1-磷酸，牛磺脱氧胆酸，lysoPE（20：5），神经肉碱，肉碱，亚油酰基肉碱，二十二碳六烯酸，lysoPC（20：4），lysoPE（18：3） ，PA（20：4），十八烷基肉碱，α-亚麻酸和lysoPA（18：0）。

结果表明，在NOAEL（0.2 mg / kg bw）下长期暴露于AA时，在代谢水平上对大鼠肝脏没有毒性作用。AA诱导肝脏氧化应激并破坏脂质代谢。肝脏组织病理学检查的结果进一步支持了代谢组学结果。