3-氯丙二醇及2,3-氧丙醇合并给药对大鼠附睾、肝、肾超微结构的影响

以每日5mg/kg的3-氯丙二醇及75mg/kg的2,3-氧丙醇同时给大鼠灌胃,连续给药2天后停药8天,共10天为一疗程。观察了3,6,9疗程结束时,附睾起始部主细胞的超微结构改变,及附睾管起始部的精子和肝脏、肾脏的超微结构。发现在3、6疗程末,附睾主细胞的高尔基复合体扁平囊变窄,大泡皱缩。在6疗程末,细胞表面的吞饮小泡和静纤毛减少。仅在3疗程见到粗面内质网扩张。9疗程的超微结构与对照比较无明显区别。结果提示,每一疗程药物引起的附睾主细胞超微结构的改变,在多数动物是可恢复的。但由于个体差异,部分动物于疗程之末,尚未完全恢复。在第6疗程末的肝脏,有部分肝细胞滑面内质网扩张,线粒体体积缩小,基质电子密度增高。这些变化可能是一种轻度的细胞损伤,这种损伤在3,9疗程均未发现,说明它与疗程长短不呈平行关系。肾尿细管上皮细胞及附睾起始部精子的超微结构,无可见改变。这一结果为阐明3-氯丙二醇及2,3-氧丙醇合并用药的抗生育作用,及对有关内脏的毒性作用,提供了形态学的依据。     

Bio-propylene glycol as value-added product from Epicerol® process

The production of chemicals from bio-based feedstocks is an emerging field of research in both industrial and academic communities. Here we present the synthesis of propylene glycol through catalytic hydrogenolysis of glycidol, obtained using a side-stream from the bio-based epichlorohydrin production plant, over Pd/C catalyst. In particular, we show the prominent effect of the acidic resin Amberlyst-15 in the selective and quantitative conversion of glycidol that permits to reach a TOF value of 162 h^?1. Propylene glycol is obtained with high yields and selectivity (> 99%) in only 1 h under mild reaction conditions. The effect of solvent is also investigated giving interesting results on the reaction selectivity. The catalytic system (Pd/C + Amberlyst-15) shows a good recyclability also after seven reaction cycles reaching high performances in term of conversion and selectivity. This allowed minimizing the amount of waste and enhancing the efficiency of the whole system.     

3-氯丙二醇和2、3-氧丙醇合并长期、间歇给药对恒河猴及大鼠毒性作用的观察

本文介绍了3-氯丙二醇和2,3-氧丙醇合并长期间歇用药对猴及大鼠的毒性观察,结果表明,以日剂量5mg/kg 3-氯丙二醇和75mg/kg 2,3-氧丙醇合并应用,可导至大鼠可逆性不育;对猴及大鼠的内脏器官、骨髓细胞增生度及微核数量、末梢血液细胞计数、分类,以及猴的染色体常规检查未见明显影响。表明合并用药有用药量小,给药时间短、起效快、毒性低等优点。     

Determination of glycidyl esters and 3-MCPD esters in edible oils by sample pretreatment with the combination of lipase hydrolysis and modified QuEChERS for GC-MS analysis

Glycidyl esters (GEs) and 3-chloroprapane-1,2-diol esters (3-MCPDEs) are processing contaminants in refined edible oils that have raised concerns globally owing to their potentially carcinogenic properties. Official analytical methods for GEs and 3-MCPDEs, such as AOCS Cd 29a-13 and AOCS Cd 29b-13, require up to 16 h for chemical hydrolysis. Also, parallel experiments should be conducted to correct for the conversion of analytes during hydrolysis in AOCS Cd 29b-13. For AOCS Cd 29c-13 with the shortest operating time, the reaction time (3.5–5.5 min) and temperature of alkaline hydrolysis should be carefully controlled, implying the accuracy may be influenced by human errors. Here, we propose a novel method based on Candida rugosa lipase hydrolysis and direct detection of free form GEs, glycidol, which was achieved by sample preparation with modified QuEChERS, to prevent side reactions in previous approaches, and also to shorten the overall sample preparation time. Glycidol was directly analyzed without halogenation and derivatization, whereas 3-MCPD required derivatization for analysis by GC-MS. Our method showed good accuracy and precision in terms of repeatability, intermediate precision, and reproducibility (inter-laboratory precision). The limit of detection (LOD) and limit of quantification (LOQ) for glycidol were 0.02 and 0.1 mg/kg, which is sufficient for practical applications. The proposed method was further compared with AOCS Cd 29c-13 by determination of GEs content in commercial oil samples and spiked samples. Our method with a streamlined procedure seems to possess potential advantage of reduced errors from operational factors. This proposed method based on direct detection of glycidol may serve as a simplified alternative for routine analysis of GEs and 3-MCPDEs in edible oils.     

Effects of 3-monochloropropane-1,2-diol (3-MCPD) and its metabolites on DNA damage and repair under in vitro conditions

3-monochloropropane-1,2-diol (3-MCPD) is a food contaminant that occurs during industrial production processes and can be found mainly in fat and salt containing products. 3-MCPD has exhibited mutagenic activity in vitro but not in vivo, however, a genotoxic mechanism for the occurrence of kidney tumors has not so far been excluded. The main pathway of mammalian 3-MCPD metabolism is via the formation of β – chlorolactatic acid and formation of glycidol has been demonstrated in bacterial metabolism. The aim of this study was to investigate genotoxic and oxidative DNA damaging effects of 3-MCPD and its metabolites, and to provide a better understanding of their roles in DNA repair processes. DNA damage was assessed by alkaline comet assay in target rat kidney epithelial cell lines (NRK-52E) and human embryonic kidney cells (HEK-293). Purine and pyrimidine base damage, H₂O₂ sensitivity and DNA repair capacity were assessed via modified comet assay. The results revealed in vitro evidence for increased genotoxicity and H₂O₂ sensitivity. No association was found between oxidative DNA damage and DNA repair capacity with the exception of glycidol treatment at 20 μg/mL. These findings provide further insights into the mechanisms underlying the in vitro genotoxic potential of 3-MCPD and metabolites.     

A pilot survey of 2- and 3-monochloropropanediol and glycidol fatty acid esters in foods on the Canadian market 2011–2013

We are presenting data on the occurrence of 2- and 3-MCPD esters and glycidol esters (MCPDEs and GEs) in more than 100 different edible fats, oils, and related products containing fats/oils, such as cookies and cooking sprays. Most of these products were purchased from retail stores in Ottawa, Canada between 2011 and 2013 in duplicate, thus allowing for evaluation of temporal trends. GEs and MCPDEs were determined by stable isotope dilution analysis using glycidol-d₅ labelled standards by LC–MS/MS in APCI mode and GC–MS in SIM mode after derivation with cyclohexanone, respectively. Unprocessed oils did not contain detectable levels of GEs or MCPDEs or contained them in trace amounts. The exception was palm oil, which contained 100–550 ng/g MCPDEs. GEs and MCPDEs content was highly variable in processed oils/fats, reaching 10.6 and 17.1 μg/g (expressed as glycidol and MCPDs equivalents, respectively). Walnut, rice bran, grape seed oils and palm oil shortening were found to have the highest levels of MCPDEs and GEs. Levels in cookies also varied greatly from 5 to 339 ng/g, expressed as glycidol equivalents and from 29 to 510 ng/g expressed as MCPD equivalents.     

A step towards bio-surfactants: Monoalkylglyceryl ethers synthesis through glycidol alcoholysis with long-chain alcohols catalyzed by Al(OTf)3

In this work we present a green synthetic pathway for the obtaining of bio-surfactants derived from glycerol. By extending a Lewis acid catalyzed reaction between glycidol and primary alcohols we obtained good conversion to the desired monoalkylglycidyl ether (MAGE) for long chain alcohols (n-octanol, n-decanol and n-dodecanol) reaching initial turnover frequency TOF up to 2633 h^?1in the case of octanol. The obtained MAGEs were fully characterized and the critical micelle concentration (CMC) was determined for all bio-surfactants using a spectrophotometric approach such as pyrene method with peak difference (P2–P7) linear fitting (octylglyceryl ether: 0.97 ± 0.02 mM; decylglyceryl ether: 0.85 ± 0.03 mM; dodecylglyceryl ether: 0.71 ± 0.04 mM).     

Late effect of developmental exposure to glycidol on hippocampal neurogenesis in mice: Loss of parvalbumin-expressing interneurons

Developmental exposure to glycidol of rats causes axonal injury targeting axon terminals in dams and transient disruption of late-stage differentiation of hippocampal neurogenesis, accompanying sustained increase in the number of reelin-producing or calretinin-expressing interneurons in offspring. The molecular mechanism of disruptive neurogenesis probably targets the newly generating nerve terminals. We previously found differences between mice and rats in the effects on hippocampal neurogenesis after developmental exposure to the same neurotoxic substances. In the present study, we examined the effects and underlying mechanisms of developmental exposure to glycidol on hippocampal neurogenesis in mice. Glycidol (800 or 1600 ppm) was administered in drinking water to mated female mice from gestational day 6 to postnatal day 21. Compared to mice drinking water without glycidol (control), the exposed dams showed axon terminal injury at both concentrations of glycidol. The offspring of the dams that had received 1600 ppm glycidol had fewer parvalbumin (PVALB)⁺ γ-aminobutyric acid (GABA)-ergic interneurons and neuron-specific nuclear protein⁺ postmitotic neurons in the hilus of the hippocampal dentate gyrus. Thus, exposure of glycidol to adult mice induced axonal degeneration equivalent to that seen in the rat; however, the target mechanism for the disruption of hippocampal neurogenesis by developmental exposure was different from that in rats, with the hilar neuronal population not affected until adulthood. Considering the role of PVALB⁺ GABAergic interneurons in the brain, developmental glycidol exposure in mice may cause a decline in cognitive function in later life, and involve a different mechanism from that targeting axon terminals in rats.     

Apoptosis is induced by sub-acute exposure to 3-MCPD and glycidol on Wistar Albino rat brain cells

3-chloropropane-1,2-diol (3-MCPD) and its toxic metabolite glycidol were classified by the International Agency for Research on Cancer (IARC) as belonging to group 2B and 2A for humans. This study aimed to determine the sub-acute toxicity of these agents. Rats were exposed to 3-MCPD at 0.87 and 10 mg/kg/bw and glycidol (2,4 and 37,5 mg/kg/bw) for 90 days. miR-21 gene expression levels significantly decreased in all group’s cerebellar tissues compared with control. Exposure to 10 mg/kg/bw 3-MCPD showed significant increases in PTEN in brain as compared to control group. The Akt gen expressions were significantly decreased in 3-MCPD and glycidol groups when compared to control group brains. Additionally, Caspase 3 and AIF immunopositivity significantly increased in 3-MCPD high dose and glycidol high dose groups in cerebellum granular layers compared to control. The results of the present study conclude that 3-MCPD and glycidol can induce apoptosis in rat brain tissue.