Search results for "TOXICITY"

[15] Glutathione and protein kinase C in peripheral nervous tissue

1995

Publisher Summary This chapter focuses on the Glutathione and Protein Kinase C (PKC) in peripheral nervous tissue. It has long been known that the redox state of thiols in peripheral neural structures might play an important role in electrophysiological function. Former studies suggested that the integrity of certain sulfhydryl groups in nerve fibers would be essential for conduction. This classic work showed data strongly suggesting that the blockade of SH groups resulted in a loss of excitability and a reduction of the resting potential, and proposed for the first time the role of SH groups in the relationship between structure and function in nerve. The histochemical localization of glut…

Novel approaches in diagnosis and therapy of Creutzfeldt-Jakob disease.

2000

The scrapie prion protein, PrP(Sc), as well as its peptide fragment, PrP106-126, are toxic on neuronal cells, resulting in cell death by an apoptotic, rather than necrotic mechanism. The apoptotic process of neuronal cells induced by prion protein supports diagnosis and offers potential targets for therapeutic intervention of the prion diseases. Among the cerebrospinal fluid (CSF) proteins, which may serve as markers of neuronal cell death associated with prion diseases, the 14-3-3 protein(s) turned out to be the most promising one. A new sensitive assay allows the detection of even small changes in the normally low levels of these proteins. In vitro, the toxic effects displayed by PrP(Sc) …

Neurodegeneration in excitotoxicity, global cerebral ischemia, and target deprivation: A perspective on the contributions of apoptosis and necrosis.

1998

In the human brain and spinal cord, neurons degenerate after acute insults (e.g., stroke, cardiac arrest, trauma) and during progressive, adult-onset diseases [e.g., amyotrophic lateral sclerosis, Alzheimer's disease]. Glutamate receptor-mediated excitotoxicity has been implicated in all of these neurological conditions. Nevertheless, effective approaches to prevent or limit neuronal damage in these disorders remain elusive, primarily because of an incomplete understanding of the mechanisms of neuronal death in in vivo settings. Therefore, animal models of neurodegeneration are crucial for improving our understanding of the mechanisms of neuronal death. In this review, we evaluate experimen…

General anaesthetics and the developing brain: an overview

2014

Various experimental studies in animals have shown that general anaesthetics are potentially toxic to the developing brain. By inducing apoptosis or interfering with neurogenesis, anaesthetic exposure during a critical period of neuronal development can have significant impact on neurocognitive function later in life. It remains controversial whether these experimental results can be transferred to human beings and this is under intensive scientific evaluation. To gain more insight into possible neurotoxic effects on the human brain of infants and small children, a number of retrospective studies have been performed. At present, there is no clear evidence that exposure to anaesthesia up to …

Mildronate and its neuroregulatory mechanisms: targeting the mitochondria, neuroinflammation, and protein expression.

2013

This review for the first time summarizes the data obtained in the neuropharmacological studies of mildronate, a drug previously known as a cardioprotective agent. In different animal models of neurotoxicity and neurodegenerative diseases, we demonstrated its neuroprotecting activity. By the use of immunohistochemical methods and Western blot analysis, as well as some selected behavioral tests, the new mechanisms of mildronate have been demonstrated: a regulatory effect on mitochondrial processes and on the expression of nerve cell proteins, which are involved in cell survival, functioning, and inflammation processes. Particular attention is paid to the capability of mildronate to stimulate…

Designing trehalose-conjugated peptides for the inhibition of Alzheimer’s Aβ oligomerization and neurotoxicity

2008

Neurotoxicity in Rat Cortical Cells Caused by N-Methyl-D-Aspartate (NMDA) and gp120 of HIV-1: Induction and Pharmacological Intervention

1996

Incubation of highly enriched neurons from rat cerebral cortex with the human immunodeficiency virus type 1 (HIV-1) coat protein gpl20 for 18 h results in fragmentation of DNA at internucleosomal linkers, a feature of apoptosis. We report that neurons respond to exposure to gp120 with an increased release of arachidonic acid via activation of phospholipase A2. This process is not inhibited by antagonists of the N-methyl-D-aspartate (NMDA) receptor channels. To investigate the influence of arachidonic acid on the sensitivity of NMDA receptor towards its aganist, low concentrations of NMDA were coadministered with arachidonic acid. Under these conditions the NMDA-mediated cytotoxicity was enh…

Imūnsupresīvās terapijas radītās neiroloģiskās blaknes pacientiem pēc nieru transplantācijas

2017

Mērķis: Neiroloģiskas blaknes dažādām imūnsupresīvām zālem nav daudz pētītas un iespējamo blakņu incidences un smaguma atšķirību identifikācia var palīdzēt optimizēt terapiju, lai palīdzētu uzlabot pacientu dzīves kvalitāti pēc transplatācijas. Šī pētījuma mērķis ir salīdzināt incidenci un smagumu neiroloģiskām blaknēm pacientiem, kuri saņem dažāda veida imūnsupresīvu terapiju pēc nieres pārstādīšanas un izvērtēt blakņu incidenci starp sieviešu un vīriešu dzimumiem. Metodes: Pētījums tika viekts Rīgas Paula Stradiņa Klīniskajā Universitātes Slimnīcā ambulatorajā nieru transplantāciju nodaļā. Pētījuma populācija sastāvēja no pacientiem, kuri vismaz sešus mēnešus pēc nieru transplantācijas sa…

Uridine uptake inhibition as a cytotoxicity test for a human hepatoma cell line (HepG2 cells): comparison with the neutral red assay

2001

International audience; This study describes a sensitive microassay for measuring cytotoxicity based on the degree of inhibition of RNA synthesis in HepG2 cells. RNA synthesis is measured by the kinetic uptake of radiolabeled uridine. A large number of compounds were tested in a wide range of concentrations. The concentration required to induce 50% inhibition of HepG2 uridine uptake rates (IC50) was determined for each compound and used to rank its potency. These IC50s were compared with IC50s measured with the neutral red assay. 2-acetylaminofluorene, benzo[a]pyrene and methylnitrosourea were not cytotoxic in the neutral red assay. Uridine uptake was always inhibited at lower concentrations…

Comparative analysis of eight cytotoxicity assays evaluated within the ACuteTox Project.

2013

A comparative analysis of eight cytotoxicity assays [the 3T3 and normal human keratinocytes Neutral Red Uptake (NRU) assay, the primary rat hepatocytes, human HepG2 and 3T3 MU assay, and the human A.704, SH-SY5Y and HepG2 cells propidium iodide (PI) assay] included in several work packages of the EU Integrated Project ACuteTox, has been carried out. The aim was to evaluate whether cells originating from liver, kidney and brain provided different in vitro acute toxicity results, and the influence of primary liver cells versus cell lines originated from the same tissue. Spearman rank correlation analysis and Hierarchical Cluster Analysis were performed based on the IC50 (50% inhibitory concen…