This study aimed to investigate the toxic effects of long-term, low-dose acephate administration on rats using ultra-performance liquid chromatography-mass spectrometry. A total of 120 male Wistar rats were randomly assigned to different groups: control; low-dose acephate (0.5 mg kg(-1) bw(-1)); middle-dose acephate (1.5 mg kg(-1) bw(-1)); and high-dose acephate (4.5 mg kg(-1) bw(-1)). The rats continuously received acephate via drinking water for 24 weeks. Rat plasma samples were collected at different time points to measure metabonomic profiles. Liver tissues were subjected to histopathological examination. The results showed that 10 metabolites in the plasma were significantly changed in the treated groups compared with those in the control group (P < 0.05 or P < 0.01). Exposure to acephate resulted in increased lysoPC (15 : 0), lysoPC (16 : 0), lysoPC (O-18 : 0), lysoPC (18 : 1(9Z)), lysoPC (18 : 0), lysoPC (20 : 4(5Z, 8Z, 11Z, 14Z)), arachidonic acid, and 12-HETE as well as decreased tryptophan and indoleacrylic acid in rat plasma. Moreover, the contents of high-density lipoprotein, low-density lipoprotein, triglyceride, total cholesterol, free fatty acids, and malondialdehyde, as well as the activities of superoxide dismutase and phospholipaseA2 in the serum, were significantly changed in the middle- and high-dose groups compared with those in the control group (P < 0.05 or P < 0.01). Histopathological examination results revealed that exposure to acephate may induce vacuolar degeneration in the liver cell cytoplasm, fat degeneration, and liver cell necrosis. These results indicated that exposure to acephate disrupted metabolism of lipids and amino acids, induced oxidative stress, caused neurotoxicity, and resulted in liver dysfunction.

This study assessed the effects of long-term, low-dose dimethoate administration to rats by ultra-performance liquid chromatography–mass spectrometry (UPLC–MS). Dimethoate (0.04, 0.12, and 0.36mg/kg body weight/day) was administered daily to male Wistar rats through their drinking water for 24weeks. Significant changes in serum clinical chemistry were observed in the middle- and high-dose groups. UPLC–MS revealed evident separate clustering among the different dose groups using global metabolic profiling by supervised partial least squares-discriminant analysis. Metabonomic analysis showed alterations in a number of metabolites (12 from urine and 13 from plasma), such as l-tyrosine, dimethylthiophosphate (DMTP), dimethyldithiophosphate (DMDTP), citric acid, uric acid, suberic acid, glycylproline, allantoin, isovalerylglutamic acid and kinds of lipids. The results suggest that long-term, low-dose exposure to dimethoate can cause disturbances in liver function, antioxidant and nervous systems, as well as the metabolisms of lipids, glucose, fatty acids, amino acids, and collagen in rats. DMTP and DMDTP, which had the most significant changes among all other studied biomarkers, were considered as early, sensitive biomarkers of exposure to dimethoate. The other aforementioned proposed toxicity biomarkers in metabonomic analysis may be useful in the risk assessment of the toxic effects of dimethoate. Metabonomics as a systems toxicology approach was able to provide comprehensive information on the dynamic process of dimethoate induced toxicity. In addition, the results indicate that metabonomic approach could detect systemic toxic effects at an earlier stage compared to clinical chemistry. The combination of metabonomics and clinical chemistry made the toxicity of dimethoate on rats more comprehensive.

To study the toxic effect of chronic exposure to acephate at low-dose levels, a metabolomics approach based on ultra-performance liquid chromatography/mass spectrometry (UPLC-MS) was applied. Three different doses of 0.5 mg/kg/day, 1.5 mg/kg/day, and 4.5 mg/kg/day acephate were administered to Wistar rats for 24 weeks. Endogenous metabolite profiles were obtained with UPLC-MS for all rats at six time points after treatment. Some metabolites like dimethylthiophosphate and uric acid in urine were detected at week 4. Dimethylthiophosphate, which had the most significant elevations compared with other biomarkers, was considered as an early, sensitive biomarker of exposure to acephate. Moreover, there were some endogenous metabolite changes, which demonstrated that the doses of 1.5 mg/kg/day and 4.5 mg/kg/day of acephate led to renal injury and perturbed the normal metabolic processes of rats, including glucose, nucleic acid, and protein metabolism. A connection between exposure to acephate and the metabolic disturbance has been found and interpreted. Our study indicates that the metabolomics approach based on UPLC-MS of urine provides more information on toxicity than the conventional toxicological evaluation methods in measuring changes and can be considered as a promising technique for the study of the toxic effect of acephate.

<正>乙酰甲胺磷由于其低毒、安全、广谱等特点,作为高毒农药甲胺磷的替代品而被广泛应用〔1〕,同时也对环境造成了不同程度的污染,使人群不可避免的暴露于乙酰甲胺磷。这种长期低剂量暴露特点对机体健康影响存在不确定性。有文献报道乙酰甲胺磷在高剂量(47.25mg/kg)染毒下,对大鼠生殖

Organophosphorous pesticides, commonly used in agriculture for achieving better quality products, are toxic substances that have harmful effects on human health. Recent research on pesticides, especially pesticide mixtures, has shown that they are one of the key environmental health issues. The aim of the present study was to investigate whether dichlorvos, acephate, dimethoate and phorate, either used separately or in combination, can induce oxidative damage in rat livers. The levels of superoxide dismutase, glutathione peroxidase, catalase and lipid peroxidation products (malondialdehyde) were used as criteria. Low, middle and high doses of pesticides in drinking water were continuously administered orally to rats ad libitum for 24 weeks. Results show that the antioxidative defense mechanisms and lipid peroxidation in the rat livers display different responses, depending on the pesticide treatments and doses. The parameters for acephate, dichlorvos, phorate and dimethoate in the low-dose group, and the corresponding low-dose co-treated group were not altered. The oxidative damage in rat livers showed different responses with increasing pesticide dose according to the different pesticide treatments. The combination group of dichlorvos, acephate, dimethoate and phorate displayed different responses compared with the single pesticide-treated group. However, these responses did not constitute the sum of the response produced by each pesticide in the liver.

The purpose of the current study was to assess the effects of long-term exposure to low levels of DDVP on the biochemical parameters and metabolic profiles of rats. Three different doses (2.4, 7.2, and 21.6mg/kgbody weight/day) of DDVP were administered to rats through their drinking water over 24 weeks. Significant changes in blood cholinesterase, creatinine, urea nitrogen, aspartate aminotransferase, alanine aminotransferase, and albumin concentrations were observed in the middle and high dose groups. Changes in the concentration of some urine metabolites were detected via ultra performance liquid chromatography–mass spectrometry (UPLC–MS). Dimethyl phosphate (DMP), which was exclusively detected in the treated groups, can be an early, sensitive biomarker for DDVP exposure. Moreover, DDVP treatment resulted in an increase in the lactobionic acid, estrone sulfate, and indoxyl sulfic concentrations, and a decrease in citric acid, suberic acid, gulonic acid, urea, creatinine, and uric acid. These results suggest that chronic exposure to low-level DDVP can cause a disturbance in carbohydrate and fatty acid metabolism, the antioxidant system, etc. Therefore, an analysis of the metabolic profiles can contribute to the understanding of the adverse effects of long-term exposure to low doses of DDVP.

Epidemiologic studies have shown that populations that consume more fruits and vegetables have lower incidences of some diseases. These health effects have largely been attributed to flavonoid intake and bioavailability. However, no published data on the estimated flavonol and flavone intake of Chinese adults are currently available. Considering reports that food frequency questionnaires (FFQs) have been shown to provide good measurements of energy, macronutrient, and micronutrient intakes, we hypothesized that FFQ may be used to estimate intake of dietary flavonol and flavone. The two 7-day 24-hour dietary recalls (24-HDRs) and plasma levels were used as reference criteria. A total of 128 subjects each completed two 7-day 24-HDR and 2 FFQs, and 92 subjects donated 2 plasma samples. Pearson correlation coefficients and the agreement of quartile categorization between the FFQ and each reference instrument were conducted. Pearson correlation coefficients between 2 FFQs were 0.62 for flavonol and 0.65 for flavone and ranged from 0.48 (quercetin) to 0.63 (luteolin) (all P < .05). Pearson correlation coefficients between FFQ and 24-HDR were 0.62 for flavonol and 0.68 for flavone and ranged from 0.36 (quercetin) to 0.63 (luteolin) (all P < .05). Between the FFQ and plasma samples, Pearson correlation coefficients were 0.52 for flavonol and 0.41 for flavone and ranged from 0.32 (quercetin) to 0.44 (kaempferol) (all P < .05). The complete and partial agreement by quartiles ranged from 70% to 89%. The findings indicate that administering FFQ is a reliable and accurate method of assessing dietary intake of flavonol and flavone.