Administration Of Sodium Azide Research Articles

Bergenin ameliorates cognitive deficits and neuropathological alterations in sodium azide-induced experimental dementia.

Background: Bergenin, 4-O-methyl gallic acid glucoside, is a bioactive compound found in the cortex of Mallotus japonicus (L.f.) Müll.Arg. along with many other natural resources including that from Bergenia species. The present study delineates the neuroprotective potential of bergenin through the modulation of PPAR-γ receptors. Method: Dementia was induced in the Wistar rats by intraperitoneal (i.p.) administration of sodium azide (12.5 mg/kg for the first 5 days followed by 10 mg/kg for the next 9 days). The rats were then exposed to the Morris water maze test to assess the effect on cognitive abilities followed by a series of biochemical and histopathological evaluations. Results: Sodium azide-treated rats exhibited a severe deterioration of memory as suggested by poor performance in the spatial learning task in addition to the enhancement of brain acetylcholinesterase potential, oxidative stress, inflammation, and amyloid-β (Aβ) accumulation. Administration of bergenin to sodium azide-treated rats significantly recovered cognition and related biochemical variations. Further, co-administration of Bisphenol A diglycidyl ether (BADGE), a PPAR-γ antagonist with bergenin challenged its neuroprotective effects. Conclusions: The findings of our study exhibit that the cognitive restoration potential of bergenin may be attributed to its modulatory effects against cholinesterase, oxidative stress, and inflammatory markers, as well as its neuroprotective actions, thus aligning it as a possible therapy for Alzheimer’s disease-related dementia. The study also fortifies the significance of PPAR-γ receptors in dementia.

Pycnogenol® Supplementation Attenuates Memory Deficits and Protects Hippocampal CA1 Pyramidal Neurons via Antioxidative Role in a Gerbil Model of Transient Forebrain Ischemia.

Pycnogenol® (an extract of the bark of French maritime pine tree) is used for dietary supplement and known to have excellent antioxidative efficacy. However, there are few reports on neuroprotective effect of Pycnogenol® supplementation and its mechanisms against ischemic injury following transient forebrain ischemia (TFI) in gerbils. Now, we examined neuroprotective effect and its mechanisms of Pycnogenol® in the gerbils with 5-min TFI, which evokes a significant death (loss) of pyramidal cells located in the cornu ammonis (CA1) region of gerbil hippocampus from 4–5 days post-TFI. Gerbils were pretreated with 30, 40, and 50 mg/kg of Pycnogenol® once a day for 7 days before TFI surgery. Treatment with 50 mg/kg, not 30 or 40 mg/kg, of Pycnogenol® potently protected learning and memory, as well as CA1 pyramidal cells, from ischemic injury. Treatment with 50 mg/kg Pycnogenol® significantly enhanced immunoreactivity of antioxidant enzymes (superoxide dismutases and catalase) in the pyramidal cells before and after TFI induction. Furthermore, the treatment significantly reduced the generation of superoxide anion, ribonucleic acid oxidation and lipid peroxidation in the pyramidal cells. Moreover, interestingly, its neuroprotective effect was abolished by administration of sodium azide (a potent inhibitor of SODs and catalase activities). Taken together, current results clearly indicate that Pycnogenol® supplementation can prevent neurons from ischemic stroke through its potent antioxidative role.

Assessing modulators of cytochrome c oxidase activity in Galleria mellonella larvae

Caterpillars of the greater wax moth, Galleria mellonella, are shown to be a useful invertebrate organism for examining mitochondrial toxicants (inhibitors of electron transport) and testing putative antidotes. Administration of sodium azide, sodium cyanide, or sodium (hydro)sulfide by intra-haemocoel injection (through a proleg) results in a dose-dependent paralysed state in the larvae lasting from <1 to ~40 min. The duration of paralysis is easily monitored, because if turned onto their backs, the larvae right themselves onto their prolegs once they are able to move again. The efficacy of putative antidotes to the three toxicants can routinely be assessed by observing shortened periods of paralysis with larvae given toxicant and antidote compared to larvae administered only the same dose of toxicant. The validity of the approach is demonstrated with agents previously shown to be antidotal towards cyanide intoxication in mice; namely, sodium nitrite and CoN4[11.3.1] (cobalt(II/III) 2,12-dimethyl-3,7,11,17-tetraazabicyclo-[11.3.1]-heptadeca-1(7)2,11,13,15-pentaenyl cation). These same compounds are shown to be antidotal towards all three toxicants in the G. mellonella caterpillars; findings that may prove important in relation to azide and sulfide poisonings, for which there are currently no effective antidotes available. The observation that sodium nitrite ameliorates cyanide toxicity in the larvae is additionally interesting because it unambiguously demonstrates that the antidotal action of nitrites does not require the involvement of methemoglobin, contributing to the resolution of an ongoing controversy.

Enhancement of cytotoxic effect on human head and neck cancer cells by combination of photodynamic therapy and sulforaphane.

Photodynamic therapy (PDT) is a method to treat cancers using photosensitizer and light. PDT has been tried for several tumors. However, the clinical applications are limited by the toxicity of photosensitizer and narrow effect. Sulforaphane (SFN) is a material of isothiocyanate group and known to have anticancer effect. We evaluated the cytotoxic effect of PDT combined with SFN on human head and neck cancer cells. We measured the cell viability, extent of apoptosis and necrosis, reactive oxygen species (ROS) generation and caspase activation. Cell viability was decreased significantly by combination treatment. Cellular apoptosis and necrosis were increased in combination treatment compared to SFN or PDT. ROS generation was also higher in combination treatment than single treatment. In combination treatment group, apoptosis and necrosis were decreased by administration of sodium azide (SA) which is scavenger of ROS. Increased caspase activation in combination treatment was also inhibited by SA. Combination of PDT and SFN led to enhanced cytotoxic effect on head and neck cancer cells. Combination treatment promoted the ROS generation, which induced cell death through activation of caspase pathway.

Proteomic Analysis of Primary Cultured Rat Cortical Neurons in Chemical Ischemia

To elucidate the molecular events involved in early ischemic neuronal death, we performed two-dimensional proteome profiling of primary cultures of rat cortical neurons following chemical ischemia induced by the administration of sodium azide under glucose-free conditions. Using a lactic dehydrogenase assay and Western blot analysis of dephosporylation of the voltage-gated potassium channel Kv2.1, we determined duration of chemical ischemia of 2h to be the relevant time-point for early ischemic neuronal death. Sixty-one proteins were differentially expressed, and 26 different proteins were identified by MALDI-TOF with Mascot database searching. The proteome data indicated that chemical ischemia altered the expression of 20 proteins that are involved in stress response/chaperone, brain development, cytoskeletal/structural proteins, metabolic enzymes, and calcium ion homeostasis. Western blotting and immunocytochemical studies of the 6-most functionally significant proteins showed that, in the ischemia-treated group, the expression of glucose-related protein 78, heat shock protein 90 alpha, and α-enolase was significantly increased, while the expression of inositol triphosphate receptor 1 and ATP synthase beta subunit was decreased. In addition, the expression of dihydropyrimidinase-like 3 showed a truncated pattern in the ischemia group. The changes in the expression of these proteins might be significant indicators of early ischemic neuronal death.

Rapid Ca2+ influx induced by the action of dibutylhydroquinone and glucagon in the perfused rat liver

Glucagon induces a slight Ca2+ efflux when administered to the perfused rat liver. However, the hormone promotes rapid and significant Ca2+ influx after the prior administration of 2, 5-di(t-butyl)-1,4-hydroquinone (BHQ), an agent that promotes Ca2+ release from the endoplasmic reticulum (ER). The concentrations of glucagon that promote Ca2+ influx are similar to those that promote glycogenolysis and gluconeogenesis in isolated hepatocytes. The permeable analogue of cAMP, but not that of cGMP, is able to duplicate the Ca2+-mobilizing effects of glucagon. The influx of Ca2+ into liver is blocked by Ni2+. Administration of sodium azide, an inhibitor of mitochondrial electron transport, also blocks the BHQ plus glucagon-induced Ca2+ influx and this is reversed when azide administration is terminated. The actions of azide are evident within 60 s after administration or withdrawal, and also occur when either oligomycin or fructose is co-administered; this provides evidence for an effect of azide independent of cellular ATP depletion. Measurement of total calcium in mitochondria that were isolated rapidly from perfused livers after the combined administration of glucagon and BHQ confirmed that large quantities of extracellular Ca2+ had entered these organelles. These experiments provide evidence that in the perfused rat liver the artificial emptying of the ER Ca2+ pool allows glucagon to promote rapid and sustained Ca2+ influx that seems to terminate in mitochondria.

Specific features of the electroretinogram of vertebrates induced by X-rays.

The net electroretinograms of dark-adapted retinas of the common frog in situ were investigated on an automated experimental system with programmed control and electronic differentiation of biopotentials with respect to the first and second derivatives. It was demonstrated that X-rays elicit an electroretinogram consisting of two components, provisionally called the first and second X-ray reactions (X-1 and X-2), which differ with respect to their parameters from electroretinograms elicited under the same conditions by red and blue light. The administration of sodium azide, sodium nitrate, monoiodo-acetate and other substances alter the X-1 and X-2 as well as the photo-induced ERGs in different ways; this indicates their relative independence and different mechanisms of the occurrence and passing of excitation across the structures of the retina, and makes it possible to partially isolate these for individual study. Thus, the assertion of a number of investigators regarding the absence of specific features in the X-ray induced electroretinograms becomes problematical. The discovery of X-ray-specific reactions in the retina makes it possible to hope that the radiological phosphene (the X-ray phosphene) may serve as a test for the determination of the individual radiational excitability of the central nervous system.