Metabolomic mechanisms of short chain chlorinated paraffins toxicity in rats.

Short chain chlorinated paraffins (SCCPs) have received increased interest worldwide since they were added to the list of controlled POPs in Annex A of the Stockholm Convention in 2017. Although many toxicological studies have already shown that SCCPs are hepatotoxic, nephrotoxic, and thyrotoxic to rodents, there have been few studies to date that have characterized changes in the metabolic pathways targeted by SCCPs. In this study, a UPLC-Q-TOF-MS based plasma metabolomics approach was used to investigate the toxicity of SCCPs in rats. Liver and kidney injury occurred rapidly after high-dose SCCP exposure, and the most relevant pathways affected were energy metabolism, amino acid metabolism, glycerophospholipid metabolism, nucleotide metabolism, and vitamin B metabolism. Exposure to SCCPs inhibited the tricarboxylic acid cycle and accelerated degradation. Fluctuating levels of phospholipids and nucleotides may have contributed to the neurotoxicity of SCCPs. In addition, the down regulation of folic acid induced by SCCPs may have led to malformations during the early development of laboratory animals. These results suggested that high exposure levels of SCCPs may have serious health risks and more research is needed to assess the health status of relevant occupational groups.

Determination of higenamine in multi-matrix by gas chromatography-mass spectrometry combined with derivatization technology.

Higenamine (HG), a cardioactive component of some foods and medicines, has been listed in the doping category by the International Olympic Committee, which may lead to misuse by athletes. We report the development of a gas chromatography-mass spectrometry (GC-MS) method for determination of HG in various matrix samples (biological samples, different forms of Chinese patent medicine, Chinese herbal medicine) based on acylation derivatization of HG by heptafluorobutyric anhydride. Under optimal conditions, the linearity of HG in the range of 5-200 ng mL-1 was acceptable (R2 > 0.999), and the limit of detection (LOD) and limit of quantitation (LOQ) for HG was 1.52 ng mL-1 and 5 ng mL-1, respectively. Low, medium, and high concentrations (25, 100 and 160 ng mL-1) of HG were added to plasma, urine, oral liquid, capsule, watered bolus, honeyed bolus and Chinese herbal medicine samples, with recovery ranging from 82.70 to 109.80%, intra-day and inter-day precisions were both less than 3.39%. The results indicated that the method had sufficient sensitivity for analysis of biological samples, and Chinese patent and herbal medicine.

Reduction of n-3 PUFAs, specifically DHA and EPA, and enhancement of peroxisomal beta-oxidation in type 2 diabetic rat heart.

BACKGROUND: There is overwhelming evidence that dietary supplementation with n-3 polyunsaturated fatty acids (PUFAs), mainly EPA (C20:5n-3) and DHA (C22:6n-3), has cardiovascular protective effects on patients with type 2 diabetes mellitus (T2DM) but not on healthy people. Because the T2DM heart increases fatty acid oxidation (FAO) to compensate for the diminished utilization of glucose, we hypothesize that T2DM hearts consume more n-3 PUFAs and, therefore, need more n-3 PUFAs. In the present study, we investigated the changes in cardiac n-3 PUFAs and peroxisomal beta-oxidation, which are responsible for the degradation of PUFAs in a high-fat diet (HFD) and low-dose streptozotocin- (STZ) induced type 2 diabetic rat model. METHODS AND RESULTS: The capillary gas chromatography results showed that all the n-3 (or omega-3) PUFAs, especially DHA (~50%) and EPA (~100%), were significantly decreased, and the n-6/n-3 ratio (~115%) was significantly increased in the hearts of diabetic rats. The activity of peroxisomal beta-oxidation, which is crucial to very-long-chain and unsaturated FA metabolism (including DHA), was significantly elevated in DM hearts. Additionally, the real-time PCR results showed that the mRNA expression of most peroxisomal beta-oxidation key enzymes were up-regulated in T2DM rat hearts, which might contribute to the reduction of n-3 (or omega-3) PUFAs. CONCLUSION: In conclusion, our results indicate that T2DM hearts consume more n-3 PUFAs, especially DHA and EPA, due to exaggerated peroxisomal beta-oxidation.