Search results for "TOXICITY"

Wirkungen von Acetazolamid, Chlorothiazid und Chlormerodrin auf die Clearance von Inulin, echtem endogenen Kreatinin, PAH und Harnstoff. Abgrenzung n…

1959

Ketorolac beats ketoprofen: lower photodecarboxylation, photohemolysis and phototoxicity

2013

Ketorolac shows reduced photohemolytic activity and low phototoxicity against human skin fibroblasts when compared to ketoprofen. The low decarboxylation quantum yield together with the efficient non-radiative deactivation of the triplet and singlet excited states of ketorolac are believed to be responsible for this behaviour.

In vivo Evaluation of [225Ac]Ac-DOTAZOL for α-Therapy of Bone Metastases

2018

Background Conjugates of bisphosphonates with macrocyclic chelators possess high potential in bone targeted radionuclide imaging and therapy. DOTAZOL, zoledronic acid conjugated to DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), demonstrated promising results in vivo in small animals as well as in first patient applications using 68Ga for diagnosis via PET and the lowenergy β-emitter 177Lu for therapy of painful bone metastases. In consideration of the fact that targeted α-therapy probably offers various advantages over the use of β--emitters, the 225Ac-labelled derivative [225Ac]Ac-DOTAZOL was synthesized and evaluated in vivo. Here, we report on radiolabelling and biodist…

Mitochondrial Toxicity in HAART: An Overview of In Vitro Evidence

2011

The combined antiretroviral therapeutic approach currently employed for the treatment of HIV infection, known as Higly Active Antiretroviral Therapy (HAART), has dramatically reduced AIDS-related morbidity and mortality. However, the adverse reactions associated with the long term use of this therapy have now become a major issue and researchers have focused on understanding the cellular mechanisms underlying these drug-induced detrimental effects which englobe a large list of different events including rash and hypersensibility reactions, hepatotoxicity, metabolic disturbances including lipodystrophy, and other metabolic syndrome-like disturbances such as hyperlactatemia, hyperlipedimia, i…

Enhanced oxidative stress and increased mitochondrial mass during Efavirenz-induced apoptosis in human hepatic cells

2010

BACKGROUND AND PURPOSE Efavirenz (EFV) is widely used in the treatment of HIV-1 infection. Though highly efficient, there is growing concern about EFV-related side effects, the molecular basis of which remains elusive. EXPERIMENTAL APPROACH In vitro studies were performed to address the effect of clinically relevant concentrations of EFV (10, 25 and 50 µM) on human hepatic cells. KEY RESULTS Cellular proliferation and viability were reduced in a concentration-dependent manner. Analyses of the cell cycle and several cell death parameters (chromatin condensation, phosphatidylserine exteriorization, mitochondrial proapoptotic protein translocation and caspase activation) revealed that EFV trig…

New ursolic and betulinic derivatives as potential cytotoxic agents.

2003

Fifteen new ursolic and betulinic triterpenoids, bearing various functionalities at C-3 and C-28 were synthesized as potential cytotoxic agents. All compounds were obtained by a hemisynthetic route via ursolic and betulinic acids. Preliminary screening of these compounds on human HT 29 colon cancer cells revealed inhibitory activity for three of them. Beta-D-Glucopyranosyl-3beta-hydroxyurs-12(13)-en-28-oate 1c, 3beta-3-(3-pyridyl)-prop-2-enoyloxyurs-12(13)-en-28-oic acid 1i and the potassium salt of 3beta-cinnamoyloxylup-20(29)-en-28-oic acid 2d demonstrated cytotoxic activity in the micromolar range: 8.0, 45.0 and 8.0 microM, respectively.

2015

Multidrug resistance is a prevailing phenomenon leading to chemotherapy treatment failure in cancer patients. In the current study two known cytotoxic pseudoguaianolide sesquiterpene lactones; neoambrosin (1) and damsin (2) that circumvent MDR were identified. The two cytotoxic compounds were isolated using column chromatography, characterized using 1D and 2D NMR, MS, and compared with literature values. The isolated compounds were investigated for their cytotoxic potential using resazurin assays and thereafter confirmed with immunoblotting and in silico studies. MDR cells overexpressing ABC transporters (P-glycoprotein, BCRP, ABCB5) did not confer cross-resistance toward (1) and (2), indic…

Ircinal E, a New Manzamine Derivative from the Indonesian Marine Sponge Acanthostrongylophora ingens

2015

Chemical investigation of the MeOH extract of the sponge Acanthostrongylophora ingens afforded the new manzamine derivative ircinal E (1), in addition to six known metabolites (2–7). The structure of the new compound was unequivocally elucidated using one- and two-dimensional NMR spectroscopy, as well as high-resolution mass spectrometry. Compounds 1–6 exhibited strong to moderate cytotoxicity against the murine lymphoma L5178Y cell line with IC50 values ranging from 2.8 to 21.7 μM.

Acid Rearrangment of Epoxy-germacranolides and Absolute Configuration of 1β,10α-Epoxy-salonitenolide

2010

The acid-catalyzed cyclization of mono epoxides of cnicin acetonide (3) was investigated. Several 6,12-eudesmanolides were obtained, and their stereochemistry established by extensive spectroscopic analyses. Chemical correlations also led to the assignment of the absolute configuration of 1β,10α-epoxy-salonitenolide (13), a previously isolated natural product. The cytotoxic activities of some compounds were determined against A549 and MCF-7 tumor cell lines. The esterified germacranolides 2–6 were selectively cytotoxic against the MCF-7 breast cancer cell line.

Nonsense codons suppression. An acute toxicity study of three optimized TRIDs in murine model, safety and tolerability evaluation.

2022

Stop mutations cause 11% of the genetic diseases, due to the introduction of a premature termination codon (PTC) in the mRNA, followed by the production of a truncated protein. A promising therapeutic approach is the suppression therapy by Translational Readthrough Inducing Drugs (TRIDs), restoring the expression of the protein. Recently, three new TRIDs (NV848, NV914, NV930) have been proposed, and validated by several in vitro assays, for the rescue of the CFTR protein, involved in Cystic Fibrosis disease. In this work, an acute toxicological study for the three TRIDs was conducted in vivo on mice, according to the OECD No.420 guidelines. Animals were divided into groups and treated with …