Antagonistic in vivo interaction of polystyrene nanoplastics and silver compounds. A study using Drosophila

Acord transformatiu CRUE-CSICSince heavy metals and micro−/nanoplastics (MNPLs) can share common environmental niches, their potential interactions could modulate their hazard impacts. The current study was planned to evaluate the potential interactions between silver compounds (silver nanoparticles or silver nitrate) and two different sizes of polystyrene nanoplastics (PSNPLs) (PS-50 and PS-500 nm), administered via ingestion to Drosophila larvae. While egg-to-adult survival was not affected by the exposure to silver compounds, PSNPLs, or their coexposures, the combined treatments succeeded to restore the delay of fly emergence induced by silver compounds. Transmission electron microscopy (TEM) and inductively coupled plasma mass spectrometry (ICP-MS) showed the ability of PSNPLs to transport silver compounds (regardless of their form) across the intestinal barrier, delivering them into the hemolymph of Drosophila larvae in a concentration exceeding that mediated by the exposure to silver compounds alone. The molecular response (gene expression) of Drosophila larvae greatly fluctuated, accordingly if exposures were administered alone or in combination. Although PSNPLs produced some oxidative stress in the hemocytes of Drosophila, especially at the highest dose (1 mM), higher levels were observed after silver exposure, regardless of its form. Interestingly, the oxidative stress of silver, especially that produced by nano‑silver, drastically decreased when coexposed with PSNPLs. Similar effects were observed regarding the DNA damage induced in Drosophila hemocytes, where cotreatment decreased the genotoxicity induced by silver compounds. This antagonistic interaction could be attributed to the ability of tiny plastic specks to confine silver, avoiding its bioavailability, and diminishing their potential impacts

Hazard assessment of ingested polystyrene nanoplastics in Drosophila larvae

Micro- and nanoplastics (MNPLs) are intentionally produced for commercial uses (primary MNPLs) or are formed from environmentally aged plastics (secondary MNPLs). Independent of their origin, all of them will finally end up in the environment constituting some of the known emergent pollutants. Despite the inert nature of plastics, questions about their potential biological effects on human health need to find sound answers. In addition, the association between the potentially induced effects and the MNPL size is also required to be known. In this context, we have used our in vivo model of Drosophila larvae and three nanopolystyrene plastics (PSNPLs) sized 50, 200, and 500 nm (PS-50, PS-200, and PS-500) to add new data to better understand the potential health risks of MNPLs. Our model has permitted us to visualize (via transmission electron microscopy, TEM) the journey of the PSNPLs administered via ingestion, their interaction with gut lumen components (including symbiotic microbiota), their uptake by gut enterocytes, their translocation through the intestinal barrier to the hemolymph, and their uptake by hemocytes. This behavior was observed for the three analyzed sizes and, for the largest sizes, changes in size/shape were observed in ingested PSNPLs. Although no relevant toxicity, as measured by the egg-to-adult viability, was observed, exposure induced a wide molecular response altering the expression of genes involved in the general stress response, in the antioxidant response and even in the genotoxicity response, as well as in genes related to the intestinal damage response. Furthermore, a general induction of ROS production and DNA damage was also detected. Interestingly, these types of responses were size-dependent with the small PSNPL size inducing a higher response

Spontaneous changes in brain striatal dopamine synthesis and storage dynamics ex vivo reveal end-product feedback-inhibition of tyrosine hydroxylase

Synaptic events are important to define treatment strategies for brain disorders. In the present paper, freshly obtained rat brain striatal minces were incubated under different times and conditions to determine dopamine biosynthesis, storage, and tyrosine hydroxylase phosphorylation. Remarkably, we found that endogenous dopamine spontaneously accumulated during tissue incubation at 37 °C ex vivo while dopamine synthesis simultaneously decreased. We analyzed whether these changes in brain dopamine biosynthesis and storage were linked to dopamine feedback inhibition of its synthesis-limiting enzyme tyrosine hydroxylase. The aromatic-L-amino-acid decarboxylase inhibitor NSD-1015 prevented both effects. As expected, dopamine accumulation was increased with L-DOPA addition or VMAT2-overexpression, and dopamine synthesis decreased further with added dopamine, the VMAT2 inhibitor tetrabenazine or D auto-receptor activation with quinpirole, accordingly to the known synaptic effects of these treatments. Phosphorylation activation and inhibition of tyrosine hydroxylase on Ser31 and Ser40 with okadaic acid, Sp-cAMP and PD98059 also exerted the expected effects. However, no clear-cut association was found between dopamine feedback inhibition of its own biosynthesis and changes of tyrosine hydroxylase phosphorylation, assessed by Western blot and mass spectrometry. The later technique also revealed a new Thr30 phosphorylation in rat tyrosine hydroxylase. Our methodological assessment of brain dopamine synthesis and storage dynamics ex vivo could be applied to predict the in vivo effects of pharmacological interventions in animal models of dopamine-related disorders.This work was supported by Spanish Government grants SAF2006-08240 (J.O.), SAF2009-12510 (J.O.), SAF2014-58396 (J.G, J.O.), SAF2017-87199-R (J.G, J.O.), SAF2016-77541-R (M.V.), The Michael J. Fox Foundation (ID15291, M.V.), “la Caixa” Foundation (ID 100010434), under the agreement LCF/PR/HR17/52150003 (M.V.). The Biological and Environmental Proteomics laboratory is a member of Proteored-PRB3 and is supported by grant PT17/0019/0008 of the PE I + D + i 2013–2016, funded by ISCIII and FEDER. M.G.S. enjoyed a Spanish government FPI fellowship. G.M received a fellowship from the China Scholarship Council. We thank the skillful technical assistance of Susana Benítez

Spontaneous changes in brain striatal dopamine synthesis and storage dynamics ex vivo reveal end-product feedback-inhibition of tyrosine hydroxylase

Altres ajuts: acord transformatiu CRUE-CSICAltres ajuts: , The Michael J. Fox Foundation (ID15291), "la Caixa" Foundation (ID 100010434), under the agreement LCF/PR/HR17/52150003Synaptic events are important to define treatment strategies for brain disorders. In the present paper, freshly obtained rat brain striatal minces were incubated under different times and conditions to determine dopamine biosynthesis, storage, and tyrosine hydroxylase phosphorylation. Remarkably, we found that endogenous dopamine spontaneously accumulated during tissue incubation at 37 °C ex vivo while dopamine synthesis simultaneously decreased. We analyzed whether these changes in brain dopamine biosynthesis and storage were linked to dopamine feedback inhibition of its synthesis-limiting enzyme tyrosine hydroxylase. The aromatic-l-amino-acid decarboxylase inhibitor NSD-1015 prevented both effects. As expected, dopamine accumulation was increased with l-DOPA addition or VMAT2-overexpression, and dopamine synthesis decreased further with added dopamine, the VMAT2 inhibitor tetrabenazine or D2 auto-receptor activation with quinpirole, accordingly to the known synaptic effects of these treatments. Phosphorylation activation and inhibition of tyrosine hydroxylase on Ser31 and Ser40 with okadaic acid, Sp-cAMP and PD98059 also exerted the expected effects. However, no clear-cut association was found between dopamine feedback inhibition of its own biosynthesis and changes of tyrosine hydroxylase phosphorylation, assessed by Western blot and mass spectrometry. The later technique also revealed a new Thr30 phosphorylation in rat tyrosine hydroxylase. Our methodological assessment of brain dopamine synthesis and storage dynamics ex vivo could be applied to predict the in vivo effects of pharmacological interventions in animal models of dopamine-related disorders

Melatonin downregulates the increased hepatic alpha-fetoprotein expression and restores pancreatic beta cells in a streptozotocin-induced diabetic rat model: a clinical, biochemical, immunohistochemical, and descriptive histopathological study

BackgroundDiabetes mellitus (DM) is a chronic metabolic disorder. Hepatopathy is one of the serious effects of DM Melatonin (MT) is a potent endogenous antioxidant that can control insulin output. However, little information is available about the potential association between melatonin and hepatic alpha-fetoprotein expression in diabetes.ObjectiveThis study was conducted to assess the influence of MT on diabetes-related hepatic injuries and to determine how β-cells of the pancreas in diabetic rats respond to MT administration.Materials and methodsForty rats were assigned to four groups at random (ten animals per group). Group I served as a normal control group. Group II was induced with DM, and a single dose of freshly prepared streptozotocin (45 mg/kg body weight) was intraperitoneally injected. In Group III, rats received 10 mg/kg/day of intraperitoneal melatonin (IP MT) intraperitoneally over a period of 4 weeks. In Group IV (DM + MT), following the induction of diabetes, rats received MT (the same as in Group III). Fasting blood sugar, glycosylated hemoglobin (HbA1c), and serum insulin levels were assessed at the end of the experimental period. Serum liver function tests were performed. The pancreas and liver were examined histopathologically and immunohistochemically for insulin and alpha-fetoprotein (AFP) antibodies, respectively.ResultsMT was found to significantly modulate the raised blood glucose, HbA1c, and insulin levels induced by diabetes, as well as the decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Furthermore, MT attenuated diabetic degenerative changes in the pancreas and the hepatic histological structure, increased the β-cell percentage area, and decreased AFP expression in the liver tissue. It attenuated diabetes-induced hepatic injury by restoring pancreatic β-cells; its antioxidant effect also reduced hepatocyte injury.ConclusionCollectively, the present study confirmed the potential benefits of MT in downregulating the increased hepatic alpha-fetoprotein expression and in restoring pancreatic β-cells in a streptozotocin-induced diabetic rat model, suggesting its promising role in the treatment of diabetes

Are bioplastics safe? : Hazardous effects of polylactic acid (PLA) nanoplastics in Drosophila

Altres ajuts: acords transformatius de la UABThe expanded uses of bioplastics require understanding the potential health risks associated with their exposure. To address this issue, Drosophila melanogaster as a versatile terrestrial in vivo model was employed, and polylactic acid nanoplastics (PLA-NPLs), as a proxy for bioplastics, were tested as a material model. Effects were determined in larvae exposed for 4 days to different concentrations (25, 100, and 400 μg/mL) of 463.9 ± 129.4 nm PLA-NPLs. Transmission electron microscopy (TEM) and scanning electron microscope (SEM) approaches permitted the detection of PLA-NPLs in the midgut lumen of Drosophila larvae, interacting with symbiotic bacteria. Enzymatic vacuoles were observed as carriers, collecting PLA-NPLs and enabling the crossing of the peritrophic membrane, finally internalizing into enterocytes. Although no toxic effects were observed in egg-to-adult survival, cell uptake of PLA-NPLs causes cytological disturbances and the formation of large vacuoles. The translocation across the intestinal barrier was demonstrated by their presence in the hemolymph. PLA-NPL exposure triggered intestinal damage, oxidative stress, DNA damage, and inflammation responses, as evaluated via a wide set of marker genes. Collectively, these structural and molecular interferences caused by PLA-NPLs generated high levels of oxidative stress and DNA damage in the hemocytes of Drosophila larvae. The observed effects point out the need for further studies aiming to deepen the health risks of bioplastics before adopting their uses as a safe plastic alternative

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population