Cholesterol is an essential component of cell membranes and the precursor for the synthesis of steroid hormones and bile acids. The synthesis of this molecule occurs partially in a membranous world ...(especially the last steps), where the enzymes, substrates, and products involved tend to be extremely hydrophobic. The importance of cholesterol has increased in the past half-century because of its association with cardiovascular diseases, which are considered one of the leading causes of death worldwide. In light of the current need for new drugs capable of controlling the levels of cholesterol in the bloodstream, it is important to understand how cholesterol is synthesized in the organism and identify the main enzymes involved in this process. Taking this into account, this review presents a detailed description of several enzymes involved in the biosynthesis of cholesterol. In this regard, the structure and catalytic mechanism of the enzymes involved in cholesterol biosynthesis, from the initial two-carbon acetyl-CoA building block, will be reviewed and their current pharmacological importance discussed. We believe that this review may contribute to a deeper level of understanding of cholesterol metabolism and that it will serve as a useful resource for future studies of the cholesterol biosynthesis pathway.
Over the last decades the inhibition of plasma cholinesterase (ChE) activity has been widely used as a biomarker to diagnose organophosphate and carbamate exposure. Plasma ChE activity is a useful ...and non-invasive method to monitor bird exposure to anticholinesterase compounds; nonetheless several studies had shown that the ChE form(s) present in avian plasma may vary greatly among species. In order to support further biomonitoring studies and provide reference data for wildlife risk-assessment, plasma cholinesterase of the northern gannet (Morus bassanus), the white stork (Ciconia ciconia) and the grey heron (Ardea cinerea) were characterized using three substrates (acetylthiocholine iodide, propionylthiocholine iodide, and S-butyrylthiocholine iodide) and three ChE inhibitors (eserine sulphate, BW284C51, and iso-OMPA). Additionally, the range of ChE activity that may be considered as basal levels for non-exposed individuals was determined. The results suggest that in the plasma of the three species studied the main cholinesterase form present is butyrylcholinesterase (BChE). Plasma BChE activity in non-exposed individuals was 0.48±0.11 SD U/ml, 0.39±0.12 SD U/ml, 0.15±0.04 SD U/ml in the northern gannet, white stork and grey heron, respectively. These results are crucial for the further use of plasma BChE activity in these bird species as a contamination bioindicator of anti-cholinesterase agents in both wetland and marine environments. Our findings also underscore the importance of plasma ChE characterization before its use as a biomarker in biomonitoring studies with birds.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Between late 2010 to early 2011, an increased mortality in gulls was observed along the northern coast of Portugal, with individuals exhibiting neurologic disorders consistent with an eventual ...anticholinesterase pesticide poisoning event. To clarify if this mortality was related to organophosphate (OP) and/or carbamate (CB) poisoning, chemical and spontaneous cholinesterase (ChE) reactivation was tested in the brain of the yellow-legged gull (Larus michahellis). Initial brain ChE activity in L. michahellis was 40.92 ± 5.23 U/mg of protein (average ± SE). Following chemical and spontaneous reactivation, ChE activity increased in average 70.38 ± 48.59 % and 131.95 ± 92.64 %, respectively. ChE reactivation was found to decrease at increasing concentrations of the oxime pyridine-2-aldoxime methochloride and dilution factor, underscoring the importance of first optimizing the assay conditions prior to its use on bird species. These results suggest that birds analysed could have been exposed to OP and CB pesticide compounds and that in most cases CB exposure appeared to be the main cause of birds poisoning. These results are an important contribution to environmental monitoring as it demonstrates the suitability of L. michaellis as sentinel species of OP and CB pesticides within an urban environment.
Engineered nanoparticles released into surface water may accumulate in sediments, potentially threatening benthic organisms. This study determined the toxicokinetics in Chironomus riparius of Ag from ...pristine silver nanoparticles (Ag NPs), a simulating aged Ag NP form (Ag2S NPs), and AgNO3 as an ionic control. Chironomid larvae were exposed to these Ag forms through water, sediment, or food. The potential transfer of Ag from larvae to adult midges was also evaluated. Results revealed higher Ag uptake by C. riparius upon exposure to Ag2S NPs, while larvae exposed to pristine Ag NPs and AgNO3 generally presented similar uptake kinetics. Uptake patterns of the different Ag forms were generally similar in the tests with water or sediment exposures, suggesting that uptake from water was the most important route of Ag uptake in both experiments. For the sediment bioaccumulation test, uptake was likely a combination of water uptake and sediment particles ingestion. Ag uptake via food exposure was only significant for Ag2S NPs. Ag transfer to the terrestrial compartment was low. In our environmentally relevant exposure scenario, chironomid larvae accumulated relatively high Ag concentrations and elimination was extremely low in some cases. These results suggest that bioaccumulation of Ag in its nanoparticulate and/or ionic form may occur in the environment, raising concerns regarding chronic exposure and trophic transfer. This is the first study determining the toxicokinetics of NPs in Chironomus, providing important information for understanding chironomid exposure to NPs and their potential interactions in the environment.
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•Toxicokinetic studies are essential to assess interactions between species and NPs.•Different exposure routes tested for Ag NPs, Ag2S NPs and AgNO3 in chironomids.•Higher uptake/bioaccumulation of Ag2S NPs than other Ag forms by chironomid larvae.•Chironomids showed similar Ag kinetics upon exposure to pristine Ag NPs and AgNO3.•Pupal exuviae are likely an elimination route for ionic and nanoparticulate Ag.
Measuring cortisol levels as a stress biomarker is essential in many medical conditions associated with a high risk of metabolic syndromes such as anxiety and cardiovascular diseases, among others. ...One technology that has a growing interest in recent years is fiber optic biosensors that enable ultrasensitive cortisol detection. Such interest is allied with progress being achieved in basic interrogation, accuracy improvements, and novel applications. The development of improved cortisol monitoring, with a simplified manufacturing process, high reproducibility, and low cost, are challenges that these sensing mechanisms still face, and for which solutions are still needed. In this paper, a comprehensive characterization of a D-shaped fiber optic immunosensor for cortisol detection based on surface plasmon resonance (SPR) enabled by gold coating is reported. Specifically, the sensor instrumentation and fabrication processes are discussed in detail, and a simulation with its complete mathematical formalism is also presented. Moreover, experimental cortisol detection tests were performed for a detection range of 0.01 to 100 ng/mL, attaining a logarithmic sensitivity of 0.65 ± 0.02 nm/log(ng/mL) with a limit of detection (LOD) of 1.46 ng/mL. Additionally, an investigation of signal processing is also discussed, with the main issues addressed in order to highlight the best way to extract the sensing information from the spectra measured with a D-shaped sensor.
Over the past decades, the presence of micronucleated blood cells has been used to detect genotoxic effects of xenobiotics in fish, amphibians and birds. This study assessed the frequency of ...micronuclei (MN) and other nuclear abnormalities in erythrocytes of individuals of Ardea cinerea and Ciconia ciconia retrieved for rehabilitation in order to evaluate the influence of age, temporal and spatial factors on the occurrence of DNA damage in Portuguese wild birds. Blood smears from 65 birds with different life-history backgrounds (e.g. geographic origin, age) were collected between 2007 and 2011 and the frequency of erythrocyte nuclear abnormalities (ENAs) was analysed. Differences in DNA damage between ages were observed to occur in C. ciconia, with chicks displaying significantly higher frequencies of ENAs (both when looking at total ENAs or only MN frequency) than juveniles and adults. Additionally, significant differences in ENAs frequencies were observed between different years and geographic origins, whereas MN frequency alone did not show significant alterations concerning spatial and temporal variations. These results suggest that the assessment of ENAs rather than MN frequency alone may be a useful and valuable tool to complement the evaluation of DNA damage in populations of birds, as prompted by individual life-history traits and environmental factors.
•The ENA assay was used for the first time to assess DNA damage in Portuguese birds.•MN frequencies above normal levels were reported in white stork and grey heron.•DNA damage in birds differed between years and location.•Younger birds exhibited higher levels of DNA damage.