Learn More
Cerebellar granule neurons maintained in medium containing serum and 25 mM K+ reliably undergo an apoptotic death when switched to serum-free medium with 5 mM K+. New mRNA and protein synthesis and formation of reactive oxygen intermediates are required steps in K+ deprivation-induced apoptosis of these neurons. Here we show that neurotrophins, members of(More)
In this study, we injected 10 mg/kg kainate i.p. into rats. This resulted in a brain injury, which we quantified in the hippocampus, the amygdala, and the pyriform cortex. Neuronal damage was preceded by a set of typical behavioral signs and by biochemical changes (noradrenaline decrease and 5-hydroxyindoleacetic acid increase) in the affected brain areas.(More)
Reduced glutathione (GSH) is a key component of the cellular defense cascade against injury caused by reactive oxygen species. Because kainic acid (KA) neurotoxicity is probably mediated at least in part by oxidative stress, we examined the influence of KA treatment on GSH content and GSH-related enzyme activities in adult rats. A single injection of KA (10(More)
Glutathione (GSH) is a key component of the cellular defence cascade against injury caused by reactive oxygen species. Kainic acid (KA) is a potent central nervous system excitotoxin. KA-elicited neuronal death may result from the generation of ROS. The present study was undertaken to characterize the role of GSH in KA-induced neurotoxicity. Cultures of(More)
The physiological roles of the pineal hormone melatonin are still not completely clarified. Recently it has been shown that melatonin is a potent, endogenous scavenger of reactive oxygen species suggesting that it might interfere with neurodegenerative processing involving free-radical formation and excitatory aminoacid release. These neuroprotective(More)
Methoxymorpholinyl doxorubicin (MMDX; PNU 152243) is a promising doxorubicin derivative currently undergoing clinical evaluation. Previous in vitro studies suggested that the compound undergoes hepatic biotransformation by cytochrome P450 (CYP) 3A into a more cytotoxic metabolite(s). The present study examined the role of CYP3A-mediated metabolism in the in(More)
PURPOSE Nemorubicin (3'-deamino-3'-[2''(S)-methoxy-4''-morpholinyl]doxorubicin; MMDX) is an investigational drug currently in phase II/III clinical testing in hepatocellular carcinoma. A bioactivation product of MMDX, 3'-deamino-3'',4'-anhydro-[2''(S)-methoxy-3''(R)-oxy-4''-morpholinyl]doxorubicin (PNU-159682), has been recently identified in an incubate of(More)
Kainic acid (KA), a potent central excitotoxin, may elicit neuronal death via generation of reactive oxygen species (ROS). The present study was undertaken to further characterize KA neurotoxicity and its relationship to ROS production and mitochondrial dysfunction. Exposure of rat cerebellar granule neurons at 14 days in vitro to 0.5 mM KA for 30 min(More)
Phosphatidylserine (PS) vesicles incorporated into rat brain synaptosomes increased total Ca2+ uptake. Total Ca2+ uptake was resolved in three components: K+ depolarization-induced Ca2+ uptake, Na+/Ca2+ exchange, and passive Ca2+ entry, which were differently affected by PS depending on the amount of incorporated phospholipid. K+ depolarization-induced Ca2+(More)
Although the induction of cytochrome P450 (CYP) has long been investigated in patients with cirrhosis, the question whether liver dysfunction impairs the response to CYP inducers still remains unresolved. Moreover, the mechanism underlying the possible effect of cirrhosis on induction has not been investigated. Since ethical constraints do not permit(More)