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Spinal administration of mGluR5 antagonist prevents the onset of bortezomib induced neuropathic pain in rat
No full textPeripheral neuropathy is a common adverse effect of bortezomib-based chemotherapy. In this study we have investigated the role played by subtype 5 of metabotropic receptors in bortezomib induced peripheral neuropathy. Rats were administered with bortezomib three times weekly at 0.20 mg/kg for a total of 4 weeks in presence or absence of mGluR5 antagonist MPEP. The animals were submitted to paw-pressure test and tail sensory nerve conduction measurement more times during the treatment and follow-up. Bortezomib treatment induced a progressively increasing hyperalgesia in rat which was accompanied by a significant reduction in sensory nerve conduction velocity (SNCV). MPEP prevented the emergence of bortezomib-induced pain and counteracted SNCV reduction when co-administered with bortezomib treatment. Spinal extracellular glutamate levels increased in rats treated with bortezomib. Bortezomib-induced onset of the hyperalgesia and SNCV decrease could be prevented by agents that promote the reuptake of glutamate maintaining spinal glutamate at basal level. Our data support the manipulation of the glutamatergic system through the mGluR5 receptor in bortezomib induced peripheral neuropathy. The use of antagonists at the mGluR5, initiated at the same time as bortezomib-chemotherapy, might reduce the number of patients who develop painful peripheral chemo-neuropathy
Glutamatergic system modulators as agents in prevention and management of chemotherapy- induced polyneuropathy
Full text linkPolyneuropathy is a common and important chemotherapy-induced adverse effect which often leads to dose modifications and impact on patients’ quality of life. Limited treatment options for prevention and management of this neuropathology stimulate further research on the topic. Recent attention has been focused on downregulation of glial glutamate transporter expression observed in spinal region of rodents treated with cancer chemotherapy drugs. Consequent extrasynaptic glutamate overflow could be considered a key element in neuropathic pathogenesis resulting in excessive activation of glutamate receptors and neuronal hyper-excitability, finally contributing to develop neuropathic condition. Recently, the onset of neuropathy in bortezomib treated rats could be prevented by preemptive administration of drugs promoting glial glutamate transporter expression and antagonism at mGlur5, a metabotropic receptor which reinforces glutamatergic transmission in presence of high extracellular glutamate concentrations. These findings point to glial-glutamate system dysregulation as a main mechanism in the pathogenesis of anticancer chemotherapy induced neuropathy
Effects of Gemcitabine (dFdC) on 5-Fluorouracil (5Fu) pharmacokinetics and pharmacodynamics.
No full textAnnual meeting of the Società Italiana di Farmacologia (SIF), Florence, Ital
Redox imbalance induced by docetaxel in the neuroblastoma SH-SY5Y cells: a study of docetaxel-induced neuronal damage
Full text linkOBJECTIVES: In cancer survivors, chemotherapy-associated adverse neurological effects are described as side effects in non-targeted tissue. We investigated the role of redox-imbalance in neuronal damage by a relative low dose of Docetaxel (DTX).METHODS: The neuroblastoma cells (SH-SY5Y cells) were exposed to DTX at a dose of 1.25 nM for 6 h. Antioxidant defenses (i.e. ascorbic acid, glutathione, and catalase) and lipid oxidation products (i.e. F2-isoprostanes) were evaluated. To investigate cell ultrastructure and tubulin localisation, transmission electron microscopy (TEM) and immunofluorescence techniques were applied.RESULTS: In the SH-SY5Y cells, DTX induced a significant reduction of total glutathione (P<0.001) and ascorbic acid (P<0.05), and an increase in both total F2-Isoprostanes (P<0.05) and catalase activity (P<0.05), as compared to untreated cells. Additionally, TEM showed a significant increase in cells with apoptotic characteristics. Immunolocalisation of tubulin showed a compromised cytoskeletal organisation.DISCUSSION: The investigated sublethal dose of DTX, to which non-targeted cells may be exposed throughout the duration of chemotherapy treatment, induces a redox imbalance resulting in a specific modulation of the antioxidant response. This study provides new insights into DTX-induced cellular mechanisms useful for evaluating whether the concomitant use of antioxidants associated with chemotherapy mitigates chemotherapy side effects in cancer survivors
Glutathione peroxidase (GSHPx) in human gastric adenocarcinoma.
No full textAnnual meeting of the Società Italiana di Farmacologia (SIF) Florence, Ital
SCHEDE DI FARMACOLOGIA GENERALE
No full textScopo delle schede è quello di fornire al lettore il materiale scientificamente adeguato per la comprensione dei concetti basilari della Farmacologia.
I principali argomenti trattati sono la farmacocinetica, la farmacodinamica e la variabilità della risposta ai farmaci.
Inoltre sono stati inseriti dei cenni relativi ad alcune discipline della farmacologia come la farmacogenetica, la farmacoeconomia e la farmacovigilanza.
La funzione delle schede è quella di permettere un approccio semplice ma completo ai concetti generali della farmacologia
Bevacizumab impairs the activity of major VEGF-carrier cells: neutrophils and platelets.
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