Potent effects of alkaloid-rich extract from Huperzia selago against sodium nitroprusside-evoked PC12 cells damage via attenuation of oxidative stress and apoptosis.

Imbalance between production and scavenging of free radicals and other reactive oxygen species (ROS) is a component of many diseases, but it is especially important in aging-related diseases of the central nervous system. Oxidative stress-induced neuronal dysfunction plays an important role in the pathomechanism of neurodegenerative disorders, including Alzheimer's and Parkinson's disease. Experimental data showed that free radical scavengers may protect the brain against oxidative modifications. The need for efficient and safe antioxidants with therapeutic potential stimulated the rise of interest in the medicinal plant products, which are a rich source of phytochemicals possessing biological activity. In our studies we focused on alkaloid fractions (AFs) isolated from club moss, Huperzia selago and Diphasiastrum complanatum, due to their beneficial activity and exclusive chemical structure. Our previous study demonstrated that selected alkaloids from Huperzia selago effectively protect macromolecules from oxidative damage. Therefore, in the present study we investigated the effects and mechanisms of action of AFs isolated from Huperzia selago and Diphasiastrum complanatum against sodium nitroprusside (SNP)-induced oxidative injury in PC12 cells. The results demonstrated that the selected AFs via reduction of nitric oxide (NO) liberation protected cells against oxidative stress, DNA and mitochondrial damage, as well as apoptosis caused by SNP. Selected AF notably decreased SNP-evoked mitochondrial polymerase γ (Polg) up-regulation. Furthermore, AF which contains Lycopodine, Serratidine, Lycoposerramine-G and (probably) Cermizine B completely inhibited the SNP-induced expression of interferon-γ (Ifng) and cyclooxygenase 2 (Ptgs2) as well as significantly down-regulated the expression of 12/15-lipoxygenase (Alox12) and tended to decrease the mRNA level of interleukin-6 gene (Il6). In conclusion, these results suggest that the AFs from Huperzia selago effectively protect PC12 cells against SNP-induced oxidative damage by adjusting the level of reactive nitrogen species, suppression of apoptosis and down-regulation of proinflammatory genes. The compounds present in these AFs could be potential candidates to develop successful drugs preventing oxidative damage and apoptosis in age-related neurodegenerative disorders.

Reversible decrease of dopamine D2 receptor density in the striatum of rats with acute hepatic failure.

The binding of a D2 receptor ligand, [3H]spiperone, was measured in striatal membranes derived from rats in which acute hepatic failure induced with thioacetamide (TAA) was associated with symptoms of hepatic encephalopathy (HE), and during recovery from HE. A 28% decrease of Bmax for the binding was measured in a symptomatic stage of HE, 1 day after TAA administration. The B(max) for [3H]spiperone binding was no longer different from control 7 days after TAA administration, when blood and brain biochemical correlates of HE were already absent. At 21 days after TAA administration, the B(max) was increased by 31% above the control level, consistent with other aspects of metabolic activation of the brain characteristic of the late recovery period from acute HE.

Acute lead intoxication in vivo affects myelin membrane morphology and CNPase activity.

The aim of the present study was to assess the sensitivity of central nervous system myelin to acute Pb-toxicity in an animal model, that imitates lead toxicity in occupationally exposed workers, or in occasional incidents of poisoning. Our results indicated that in vivo acute lead intoxication affected both the morphology of myelin and enzymatic activity of the myelin marker, CNPase (2'3'-cyclic nucleotide 3'-phosphodiesterase). The multilayered structure of myelin sheaths was regionally disturbed, with loosely arranged membranes or ovoid-shaped swollen fragments. The activity of CNPase was diminished and Michaelis-Menten kinetics showed a decreased affinity and lower velocity of the enzyme. These data suggest that the disturbances in CNPase activity may contribute, in some extent, to the changes in myelin morphology observed in acute Pb-intoxication.

Lead as an inductor of changes in the citrate transport to rat brain synaptic mitochondria.

The aim of the experiments presented here was to discern whether prolonged consumption of leaden water, that imitates environmental exposure, affects citrate transport to synaptic mitochondria. Our results indicate that during chronic lead intoxication both the velocity and the affinity of citrate transport to synaptic mitochondria decreased affecting the operation of Krebs cycle and consequently energetic processes in these mitochondria.

Is lead toxicosis a reflection of altered energy metabolism in brain synaptosomes?

The aim of the experiments presented here was to discern whether prolonged consumption of leaden water, that imitates environmental exposure, affects some energetic parameters in nerve endings of adult rat brains. Our results indicated that during chronic lead intoxication the oxidation chain of synaptic mitochondria remains intact. The oxygen consumption by synaptosomes and activity of cytochrom oxidase in synaptic and pericarionic mitochondria obtained from intoxicated rats did not change in comparison to those from the control samples. Compared with the control samples, the concentration of ATP decreased and the concentration of creatine phosphate (CrP) increased drastically in fractions obtained from Pb2+ intoxicated animals with simultaneously increased activity of creatine kinase (CK). It seems likely that, the CrP/Cr/CK system constitutes a satisfactory regulatory mechanism for chronic Pb2+ toxicity effects on energy metabolism in nerve endings of the adult rats.