Search results for "Ditiocarb"

Endothelium- and nitric oxide-dependent vasorelaxing activities of gamma-butyrobetaine esters: possible link to the antiischemic activities of mildro…

2004

Mildronate [3-(2,2,2-trimethylhydrazine) propionate (THP)] is an antiischemic drug acting mainly via inhibition of fatty acid beta-oxidation. Some effects of the drug cannot be explained by the latter mechanism. We tested the eventual nitric oxide (NO) dependence of the mildronate action. Mildronate, gamma-butyrobetaine (GBB) and GBB methyl ester induced transient increases in nitric oxide (NO) concentrations in rat blood and myocardium. In vitro, these compounds neither modified the activities of purified neuronal and endothelial recombinant nitric oxide synthases (NOSs) nor were able to interact with their active site. GBB induced vasodilatation at high concentrations only (EC50 = 5 x 10(…

Zinc chelation during non-lesioning overexcitation results in neuronal death in the mouse hippocampus

2003

In the hippocampus, chelatable zinc is accumulated in vesicles of glutamatergic presynaptic terminals, abounding specially in the mossy fibers, from where it is released with activity and can exert a powerful inhibitory action upon N-methyl-D-aspartate receptors. Zinc is therefore in a strategic situation to control overexcitation at the zinc-rich excitatory synapses, and consequently zinc removal during high activity might result in excitotoxic neuronal damage. We analyzed the effect of zinc chelation with sodium dietyldithiocarbamate under overexcitation conditions induced by non-lesioning doses of kainic acid in the mouse hippocampus, to get insight into the role of zinc under overexcita…

Calretinin/PSA-NCAM immunoreactive granule cells after hippocampal damage produced by kainic acid and DEDTC treatment in mouse.

2003

There is a dramatic increase in the number of lightly immunoreactive calretinin cells in the granular layer of the dentate gyrus of the mouse hippocampus 1 day after excitotoxic injury using kainic acid combined with the zinc chelator diethyldithiocarbamate. At 7 days after treatment, these cells are strongly immunoreactive for calretinin and for the polysialated form of the glycoprotein neural cell adhesion molecule (PSA-NCAM). The reexpression of calretinin and PSA-NCAM after treatment corresponds well with the loss of input from the damaged hilar mossy cells. These cells could be considered immature granule cells since they are immunoreactive to markers for immature cells such as PSA-NCA…

Effect of cytochrome P450 inhibitors (diethyl dithiocarbamate, ketoconazole and grapefruit juice) on the pharmacokinetics of all-trans-retinoic acid.

2004

Diethyl dithiocarbamate (DEDTC) has been reported to be a more powerful inhibitor of all-trans-retinoic acid (ATRA) in vitro metabolism than the well-established cytochrome P450 (CYP) inhibitor ketoconazole (KC). In recent years grapefruit juice (GJ) has been shown to be able to increase the oral bioavailability of several drugs by inhibiting intestinal CYP. This study investigated the in vivo effect of these CYP inhibitors on the pharmacokinetics of ATRA. The latter was administered to rats as a constant-rate intravenous (i.v.) infusion (0.48 mg h(-1) kg(-1)) during 10 h and orally (1.6 mg kg(-1)). DEDTC (320 mg kg(-1) x 2 i.v., 6.4 and 32 mg kg(-1) per os (p.o.)) did not change the ATRA c…

Chelation of synaptic zinc induces overexcitation in the hilar mossy cells of the rat hippocampus.

2004

Complete removal of synaptic zinc by the chelator dietyldithiocarbamate (DEDTC; 500 mg/kg i.p.) in rat was followed by convulsive behaviour including wet dog shakes alternating immobility. Histological analysis 1 day after DEDTC administration detected expression of heat shock protein in the hippocampus restricted to hilar cells. These cells colocalize the marker for neurons and the glutamate receptor GluR2/3 showing that they are excitatory neurons. Additionally, they projected to the contralateral dentate gyrus. Therefore, they correspond to hilar mossy cells. These data show that the synaptic zinc has a role in normal hippocampus avoiding overexcitation, that would impair functionality e…

Neural overexcitation and implication of NMDA and AMPA receptors in a mouse model of temporal lobe epilepsy implying zinc chelation.

2006

Summary: Purpose: Zinc chelation with diethyldithiocarbamate (DEDTC) during nondamaging kainic acid administration enhances excitotoxicity to the level of cell damage. The objective of this work was to study the developing of the lesion in this model of temporal lobe epilepsy and the implications of the different types of glutamate receptors. Methods: The antagonist of the N-methyl-d-aspartate (NMDA) receptor MK-801, and the antagonist of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor GYKI52466, were used concomitantly with intraperitoneal administration of kainic acid (15 mg/kg) followed by DEDTC (150 mg/kg) in mouse. The animals were killed at different times from 4 …

Determinazione tramite GC/MS di etilentiourea (ETU) in urine di lavoratori di una azienda vitivinicola siciliana esposti a mancozeb

2008

Irreversible protein binding of acrylonitrile.

1981

1. After i.p. injection of [2,3-14C]acrylonitrile to rats, a significant portion of radioactivity becomes irreversibly attached to proteins of liver, lung, spleen and other tissues. 2. When rat liver microsomes were incubated with [2,3-14C]acrylonitrile, a time-dependent irreversible binding of radioactivity occurred to microsomal proteins. This binding was not dependent on NADPH. A high extent of binding to heat-inactivated microsomes indicated that no enzymic metabolic step was involved. 3. The irreversible binding of [2,3-14C]acrylonitrile to rat liver microsomal protein in vitro was inhibited by thiols (cysteine, glutathione, mercaptoethanol). The greatest inhibitory potency was display…