Search results for " Toxicity"
showing 10 items of 346 documents
The purine analogues abacavir and didanosine increase acetaminophen-induced hepatotoxicity by enhancing mitochondrial dysfunction
2016
Background NRTIs are essential components of HIV therapy with well-documented, long-term mitochondrial toxicity in hepatic cells, but whose acute effects on mitochondria are unclear. As acetaminophen-induced hepatotoxicity also involves mitochondrial interference, we hypothesized that it would be exacerbated in the context of ART. Methods We evaluated the acute effects of clinically relevant concentrations of the most widely used NRTIs, alone or combined with acetaminophen, on mitochondrial function and cellular viability. Results The purine analogues abacavir and didanosine produced an immediate and concentration-dependent inhibition of oxygen consumption and complex I and III activity. Th…
Correlation between polymorphism of TYMS gene and toxicity response to treatment with 5-fluoruracil and capecitabine
2020
Tumorigenesis is a multiphasic process in which genetic alterations guide the progressive transformation in cancer cells1. In order to evaluate the possible correlation between some gene variants and the risk of the toxicity development onset, two of the polymorphisms of the thymidylate synthase (TYMS), rs34743033 (2R/3R) and rs16430 (DEL/INS) were investigated. We enrolled in our study 47 patients from the Hospital of Sicily. Our preliminary findings suggest that there could be a linkage between the genotypes discussed and the development of the toxicity following the chemotherapy treatment. These results need to be confirmed by further studies, however this short paper offers some initial…
Modeling Chronic Toxicity: A Comparison of Experimental Variability With (Q)SAR/Read-Across Predictions
2018
This study compares the accuracy of (Q)SAR/read-across predictions with the experimental variability of chronic lowest-observed-adverse-effect levels (LOAELs) from in vivo experiments. We could demonstrate that predictions of the lazy structure-activity relationships (lazar) algorithm within the applicability domain of the training data have the same variability as the experimental training data. Predictions with a lower similarity threshold (i.e., a larger distance from the applicability domain) are also significantly better than random guessing, but the errors to be expected are higher and a manual inspection of prediction results is highly recommended.
Antipoxvirus Activity Evaluation of Optimized Corroles Based on Development of Autofluorescent ANCHOR Myxoma Virus
2021
International audience; A series of 43 antiviral corrole-based molecules have been tested on myxoma virus (Lausanne-like T1MYXV strain). An autofluorescent MYXV, with an ANCHOR cassette, has been used for the studies. A(2)B-fluorocorroles display various toxicities, from 40 being very toxic (CC50 = 1.7 mu M) to nontoxic 38 (CC50 > 50 mu M), whereas A(3)-fluorocorroles, with one to three fluorine atoms, are not toxic (with the exception of corroles 9, 10, and 22). In vitro, these compounds show a good selectivity index when used alone. Corrole 35 seems to be the most promising compound, which displays a high selectivity index with the lowest IC50. Interestingly, this "Hit" corrole is easy to…
Apoptosis of Hepatocytes: Relevance for HIV-Infected Patients under Treatment.
2021
Due to medical advances over the past few decades, human immunodeficiency virus (HIV) infection, once a devastatingly mortal pandemic, has become a manageable chronic condition. However, available antiretroviral treatments (cART) cannot fully restore immune health and, consequently, a number of inflammation-associated and/or immunodeficiency complications have manifested themselves in treated HIV-infected patients. Among these chronic, non-AIDS (acquired immune deficiency syndrome)-related conditions, liver disease is one of the deadliest, proving to be fatal for 15–17% of these individuals. Aside from the presence of liver-related comorbidities, including metabolic disturbances and co-infe…
Molecular strategies to increase yeast iron accumulation and resistance.
2018
All eukaryotic organisms rely on iron as an essential micronutrient for life because it participates as a redox-active cofactor in multiple biological processes. However, excess iron can generate reactive oxygen species that damage cellular macromolecules. The low solubility of ferric iron at physiological conditions increases the prevalence of iron deficiency anemia. A common strategy to treat iron deficiency consists of dietary iron supplementation. The baker’s yeast Saccharomyces cerevisiae is used as a model eukaryotic organism, but also as a feed supplement. In response to iron deficiency, the yeast Aft1 transcription factor activates cellular iron acquisition. However, when constituti…
Nanoparticle decoration impacts airborne fungal pathobiology
2018
Airborne fungal pathogens, predominantly Aspergillus fumigatus, can cause severe respiratory tract diseases. Here we show that in environments, fungal spores can already be decorated with nanoparticles. Using representative controlled nanoparticle models, we demonstrate that various nanoparticles, but not microparticles, rapidly and stably associate with spores, without specific functionalization. Nanoparticle-spore complex formation was enhanced by small nanoparticle size rather than by material, charge, or "stealth" modifications and was concentration-dependently reduced by the formation of environmental or physiological biomolecule coronas. Assembly of nanoparticle-spore surface hybrid s…
Transcriptional response of Erwinia amylovora to copper shock: in vivo role of the copA gene
2017
Fire blight is a devastating plant disease caused by the bacterium Erwinia amylovora, and its control is frequently based on the use of copper-based compounds whose mechanisms of action are not well known. Consequently, in this article, we investigate the response of E. amylovora to copper shock by a whole-genome microarray approach. Transcriptional analyses showed that, in the presence of copper, 23 genes were increased in expression; these genes were classified mainly into the transport and stress functional categories. Among them, the copA gene was strongly induced and regulated in a finely tuned manner by copper. Mutation of copA, soxS, arcB, yjcE, ygcF, yhhQ, galF and EAM_3469 genes re…
Toxicity of biomining effluents to Daphnia magna: Acute toxicity and transcriptomic biomarkers
2018
Increasing metal consumption is driving the introduction of new techniques such as biomining to exploit low grade ores. The biomining impacts notably aquatic ecosystems, yet, the applicability of ecotoxicological tests to study the complex mixture effects of mining waters is insufficiently understood. The aim of the present work was to test if transcriptomic biomarkers are suitable and sensitive for the ecotoxicity assessment of biomining affected waters. The study site had been affected by a multimetal biomine, and the studied water samples formed a concentration gradient of contamination downstream from the biomining site. Cadmium and nickel were used as positive controls in the toxicity …
What can visual caregivers expect with patients treated for SARS-CoV-2? An analysis of ongoing clinical trials and ocular side effects
2020
Within the COVID-19 pandemic context, the WHO has proposed a list of medicines to treat patients with severe acute respiratory syndrome (SARS-CoV-2). An analysis of their ocular side effects was performed. Only chloroquine and hydroxychloroquine were found to have an ocular impact in the medium and long-term. Detailed search strategies were performed in EMBASE, MEDLINE, SCOPUS and WOS Core Collection. Additionally, the worldwide ongoing clinical trials including chloroquine or hydroxychloroquine were evaluated, and their proposals of drug administration and exclusion criteria analyzed. In general, high maximum cumulative doses of chloroquine or hydroxychloroquine are being used for a short…