Arsenic pollution has become increasingly severe. It occurs as the result of geological processes and different human activities. Arsenic toxicity at the respiratory level occurs mainly by inhalation of products of coal combustion. The aim of this study was to evaluate sodium arsenite (As3+) toxicity in murine alveolar macrophages (AMs) in vitro and its association with the alterations in cell metabolism.
No changes in viability, apoptosis or cell area were detected in AMs treated with As3+ concentrations up to 2 μM for 24–96 h. A marked decrease in these end-points was observed for As3+ concentrations ranging from 2.5 μM to 10 μM.
Regarding the dynamics of the endo-exocytic process triggered by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell incorporation, no variations were detected for As3+ concentrations lower than 2 μM while higher concentrations markedly modified this response.
MTT specific activity, as a measure of cell metabolic activity, was not modified irrespective of the As3+ concentration assayed. However, nitroblue tetrazolium (NBT) specific activity, as a measure of superoxide anion generation, is responsive but only to low As3+ doses.
Although this study focuses on lung macrophages, the effects of As3+ described herein may also apply to the response of macrophages residing in other organs.
Arsenite modifies the metabolic and the oxidative status of AMs in vitro. When macrophages are in an As3+ rich medium, they exhibit a reduction in respiratory burst levels and lose their intrinsic capacity to respond to toxicants. 相似文献
In normal adult cats we measured the density of staining for the activity of succinate dehydrogenase (SDH staining) in ventral horn cells of different sizes. The measurements were restricted to that part of the lumbar ventral horn (L6-L7) which is known to contain motoneurones of the peroneal nerve. A statistically significant tendency was found for the SDH staining to be denser in smaller than in larger neurones within the size range of a motoneurones (soma diameter greater than 40 microns). These results are consistent with recently published evidence for ventral horn cells of rats and qualitatively similar relationships between size and SDH staining have also been observed among skeletal muscle fibres (confirmed for mixed muscle of cat in present study). In hindlimb muscles, size as well as SDH staining are known to be markedly activity-dependent. We tested whether this is the case for peroneal motoneurones as well by analyzing the effects of chronic nerve stimulation on the properties of neurones within the appropriate region of the ventral horn. Prior to the final acute experiment, these cats had been subjected to a left-side dorsal rhizotomy and hemispinalization. By aid of a portable mini-stimulator, the left-side common peroneal nerve was activated by repetitive pulses during 50% of total time per day (intra-activity rate: 10, 20 or 40 Hz). After 8 weeks of such treatment, cell sizes as well as the densities of SDH staining showed hardly any differences between peroneal ventral horn cells of the experimental and control sides of the spinal cord.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
Changes in the distribution of the iron-binding protein lactotransferrin have recently been described in the central nervous
system during a variety of neurodegenerative disorders. To investigate whether lactotransferrin is associated with the neuropathological
changes that characterize Parkinson’s disease, we analyzed the distribution of this protein in the mesencephalon of neurologically
normal individuals and patients affected with Parkinson’s disease using quantitative immunohistochemical methods. High levels
of lactotransferrin were observed in a large population of neurons in the substantia nigra of control cases. Lactotransferrin-positive
neurons were severely affected by the neurodegenerative process that occurs in Parkinson’s disease as indicated by a severe
decrease in the number of immunolabeled neurons in all of these cases. Quantitative analysis also demonstrated higher immunolabeling
levels of lactotransferrin in the surviving neurons in the substantia nigra and ventral tegmental area of Parkinson’s disease
cases compared to control cases. These results suggest that lactotransferrin may participate actively in the mechanism of
neuronal degeneration in Parkinson’s disease.
Received: 16 October 1995 / Revised, accepted: 1 December 1995 相似文献
The effects of KB-2796, 1-[bis(4-fluorophenyl)methyl]-4-(2,3,4-trimethoxybenzyl)piperazine-2HCl, on the low- and high-voltage activated Ca2+ currents (LVA and HVA ICa, respectively) and on oxidative metabolism were studied in neurons freshly dissociated from rat brain. KB-2796 reduced the peak amplitude of LVA ICa in a concentration-dependent manner with a threshold concentration of 10−7 M when the LVA ICa was elicited every 30 s in the external solution with 10 mM Ca2+. The concentration for half-maximum inhibition (IC50) was 1.9 × 10−6M. At 10−5 M or more of KB-2796, a complete suppression of the LVA ICa was observed in the majority of neurons tested. There was no apparent effect on the current-voltage (I-V) relationship and the current kinetics. KB-2796 delayed the reactivation and enhanced the inactivation of the Ca2+ channel for LVA ICa voltage- and time-dependently, suggesting that KB-2796 preferentially binds to the inactivated Ca2+ channel. KB-2796 at a concentration of3.0 × 10−6M also decreased the peak amplitude of the HVA ICa without shifting the I-V relationship. In addition, KB-2796 reduced the oxidative metabolism (the formation of reactive oxygen species) of the neuron in a concentration-dependent manner with a threshold concentration of3 × 10−6M. It is suggested that the inhibitory action of KB-2796 on the neuronal Ca2+ influx and the oxidative metabolism, in combination with a cerebral vasodilatory action, may reduce ischemic brain damage. 相似文献
There is compelling evidence that the etiology of Alzheimer’s disease (AD) involves characteristic amyloid-β (Aβ) deposition, oxidative stress, and anomalous metal–Aβ protein interaction. New studies have implicated redox active metals such as copper, iron, and zinc as key mediating factors in the pathophysiology of Alzheimer’s disease. There is also evidence that drugs with metal chelating properties could produce a significant reversal of amyloid-β plaque deposition in vitro and in vivo. This paper reviews current observations on the etiologic role of zinc in AD. We also discuss the interactions of zinc and copper with Aβ, a factor that purportedly facilitates disease processes. Finally, we review the protective role of zinc against Aβ cytotoxicity and hypothesize how the apparent effect of zinc on AD pathology may be paradoxical, The Zinc Paradox. Indeed, complex pathologic stressors inherent to the Alzheimer’s diseased brain dictate whether or not zinc will be neuroprotective or neurodegenerative. Further research on the zinc paradox in AD is needed in order to elucidate the exact role zinc plays in AD pathogenesis. 相似文献
Oligonol is produced from the oligomerization of polyphenols (typically proanthocyanidin from a variety of fruits such as lychees, grapes, apples, persimmons, etc.) and contains catechin-type monomers and oligomers of proanthocyanidins. The ability of Oligonol to affect infection-dependent eye inflammation, locomotion and longevity in senescence-accelerated prone mice (SAMP8) (a model of senescence acceleration and geriatric disorders with increased oxidative stress and neuronal deficit) was investigated. Oligonol (60mg/kg) significantly modulated the extent of inflammation scores in the eye of SAMP8 mice. Examination of the mice indicated infection with mouse hepatitis virus and pinworm (Syphacia obvelata) in both males and females and with the intestinal protozoa (trichomonad) in males. A comparison of the two groups (using log-rank test) and the difference in the mean life span between groups (using Student's t-test) indicated significant differences in survival (p=0.043) and the mean life span (p=0.033) in male SAMP8 mice. Oligonol increased the mean life span and this was statistically significant. In the open-field locomotive test, the 7-week-old SAMP8 mice crossed more than 40 partitioned lines in 1min. At 48-week-old control untreated male SAMP8 crossed 2 lines. The Oligonol-treated 48-week-old male SAMP8 mice crossed 17 lines however. The improved locomotive activity was statistically significant even after 36weeks in the Oligonol-treated male SAMP8 but this was not the case throughout the time course of the study in the Oligonol-treated female SAMP8. Thus Oligonol treatment to SAMP8 mice modulated the severity of infection-dependent inflammation, prolonged life-span and significantly improved locomotive activity indicating potential benefit to aging-associated diseases such as Alzheimer's or Parkinson's diseases. This presents potential for further research to define infection-dependent inflammation associated with degenerative conditions and the molecular mechanism of dietary antioxidant protection. 相似文献