Cumulative dietary risk assessment of chronic acetylcholinesterase inhibition by residues of pesticides.

A retrospective cumulative risk assessment of dietary exposure to pesticide residues was conducted for chronic inhibition of acetylcholinesterase. The pesticides considered in this assessment were identified and characterised in a previous scientific report on the establishment of cumulative assessment groups of pesticides for their effects on the nervous system. The exposure assessments used monitoring data collected by Member States under their official pesticide monitoring programmes in 2016, 2017 and 2018, and individual food consumption data from 10 populations of consumers from different countries and from different age groups. Exposure estimates were obtained by means of a two-dimensional probabilistic model, which was implemented in SAS ® software. The characterisation of cumulative risk was supported by an uncertainty analysis based on expert knowledge elicitation. For each of the 10 populations, it is concluded with varying degrees of certainty that cumulative exposure to pesticides contributing to the chronic inhibition of acetylcholinesterase does not exceed the threshold for regulatory consideration established by risk managers.

Supplemental antioxidants do not ameliorate colitis development in HLA-B27 transgenic rats despite extremely low glutathione levels in colonic mucosa.

BACKGROUND: Oxidative stress is presumed to play an important role in inflammatory bowel disease (IBD). Accordingly, antioxidant supplementation might be protective. Dietary calcium inhibited colitis development in HLA-B27 transgenic rats, an animal model mimicking IBD. As antioxidants might act at mucosa level and calcium predominantly in the gut lumen, we hypothesize that the combination has additive protective effects on colitis development. METHODS: HLA-B27 rats were fed a control diet or the same diet supplemented with the antioxidants glutathione, vitamin C, and vitamin E, or supplemented with both antioxidants and calcium. Oxidative stress in colonic mucosa, colonic inflammation, intestinal permeability, and diarrhea were quantified. RESULTS: Intestinal permeability, diarrhea, myeloperoxidase, and interleukin-1ß levels were significantly lower in rats fed both antioxidants and calcium compared to rats supplemented with antioxidants only. No beneficial effects were observed in rats fed the diet supplemented with antioxidants only. Strikingly, despite extremely low colonic mucosal glutathione levels in HLA-B27 rats, there was no oxidative stress-related damage. Subsequent analyses showed no defect in expression of glutathione synthesis genes. Additional experiments, comparing young and older HLA-B27 rats, showed that glutathione levels and also reactive oxygen species production decreased with progression of intestinal inflammation. CONCLUSIONS: Antioxidant supplementation was ineffective in HLA-B27 rats despite low mucosal glutathione levels, because colitis development did not coincide with oxidative stress in this model. This indicates that the neutrophilic respiratory burst, and thus innate immune defense, is compromised in HLA-B27 rats. As supplementation with both calcium and antioxidants attenuated colitis development, we speculate that this protective effect is attributed to calcium only.

No evidence for oxidative stress in patients on home parenteral nutrition.

BACKGROUND & AIMS: Patients on total parenteral nutrition depend on the composition of the nutritional formulation for maintenance of their oxidant-antioxidant balance. The present observational study was conducted to evaluate a substantial part of our patient population for evidence of oxidative stress. METHODS: Venous blood samples were obtained from 41 patients on home parenteral nutrition (HPN) and 41 healthy controls. Glutathione in plasma and whole blood, glutathione peroxidase and superoxide dismutase in erythrocytes and total plasma antioxidant capacity were measured to assess the antioxidant status. Oxidant status was evaluated by measuring the production of reactive oxygen species by leukocytes. Oxidative damage was assessed by measuring lipid peroxidation and protein oxidation products. RESULTS: Patients on HPN showed some signs of increased oxidative stress, however, there were no signs for oxidative damage, compared with healthy controls. In addition, activity of any underlying disease was not associated with increased oxidative stress. CONCLUSIONS: The current treatment regime for patients on HPN at our center apparently prevents the development of significant oxidative damage, despite signs of some oxidative stress. Based on these data, adaptations in the composition of parenteral nutritional formulations do not seem mandatory.