Gamma rays and sodium azide induced variations in bio-physiological and agronomical traits in linseed (Linum usitatissimum L.).

Linseed is a valuable oilseed crop with huge therapeutic importance due to its high content of omega-3 fatty acids in the form of Alpha-linolenic acid (ALA). It is a self-pollinated crop with a low-yielding potential that restricts its improvement endeavors. To overcome low-yielding potential, individual and combination treatments of gamma rays and sodium azide were employed in widely grown linseed varieties. The results revealed a dose-dependent decline in seed germination, seedling height, pollen fertility, chlorophyll, and carotenoid contents and a dose-independent decline in carbonic anhydrase activity. Bio-physiological parameters decreased substantially in combination treatments compared to individual treatments of gamma rays and sodium azide. In contrast, lower doses of gamma rays, sodium azide, and their combinations effectively increased mean values of yield and yield-attributing traits in a few putative mutants. Such putative mutants represent a valuable genetic resource that could be used in future breeding programs for the genetic improvement of linseed and related medicinal plants.

A New Family of High Oxidation State Antiperovskite Nitrides: La3MN5 (M=Cr, Mn and Mo).

Three new nitrides La3MN5 (M=Cr, Mn, and Mo) have been synthesized using a high pressure azide route. These are the first examples of ternary Cs3CoCl5-type nitrides, and show that this (MN4)NLa3 antiperovskite structure type may be used to stabilise high oxidation-state transition metals in tetrahedral molecular [MN4]n- nitridometallate anions. Magnetic measurements confirm that Cr and Mo are in the M6+ state, but the M=Mn phase has an anomalously small paramagnetic moment and large cell volume. Neutron powder diffraction data are fitted using an anion-excess La3MnN5.30 model (space group I4/mcm, a=6.81587(9) Šand c=11.22664(18) Šat 200 K) in which Mn is close to the +7 state. Excess-anion incorporation into Cs3CoCl5-type materials has not been previously reported, and this or other substitution mechanisms may enable many other high oxidation state transition metal nitrides to be prepared.

A case report of sodium azide-induced myopericarditis.

Background: Sodium azide exposures are rare but can be lethal as the substance inhibits complex IV in the electron transport chain, blocking adenosine-triphosphate (ATP) synthesis. Sodium azide is mostly used as a propellant in vehicular airbags but is also used in laboratory, pharmacy, and industrial settings. No known antidote exists and its cardiotoxic effects are poorly described in the literature. Case summary: We describe the case of a 31-year-old patient with major depressive disorder presenting with altered mental status after ingestion of an unknown amount of sodium azide. Although initially chest pain free, she developed pleuritic chest pain 48 h after ingestion. This was accompanied by new diffuse ST elevations on the electrocardiogram and serum troponin elevations concerning for myopericarditis. Treatment was pursued with a 14-day course of colchicine resulting in complete symptom resolution within 4 days of treatment initiation. The patient's transthoracic echocardiogram was only notable for a preserved left ventricular ejection fraction (LVEF). Discussion: Cardiac toxicity after sodium azide ingestion usually occurs days after ingestion and has been previously described in the forms of heart failure with reduced ejection fraction complicated by cardiogenic shock. We describe the first case of sodium azide-induced myopericarditis with a preserved LVEF treated with colchicine. Colchicine is an established treatment for pericarditis, but its inhibition of endocytosis, an ATP-dependent cellular function, could be mechanistically relevant to this case.

Heterogeneous photocatalytic degradation of antiviral drug didanosine mediated by rose bengal and TiO2 nanoparticles.

There is a great concern among the researcher to remove the problem of the persistent organic pollutants in wastewater. Pharmaceutical agrochemical and personal care products are generally considered Persistent organic pollutants. Therefore, it is a matter of concern to develop new techniques how to remove these pollutants safely at low cost. This study mainly focuses on the commonly used antiviral drug didanosine and one most commonly used dye rose bengal. In this study, an organic dye rose bengal and TiO2 nanoparticles have been used in combination with UV light to achieve the photodegradation of selected pharmaceutical products and the dye was also degraded by using TiO2 Nanoparticles. The formation of three oxidation products was detected by using a very popular separation technique thin layer and column chromatography. The isolated photoproduct was characterized by using advanced characterization techniques like FTIR (Fourier transform infrared spectroscopy), UV Spectroscopy, and Proton and 13C NMR (Nuclear Magnetic Resonance spectroscopy). The role of singlet oxygen as an active species in this reaction was confirmed by using D2O as a reaction medium. The role of singlet oxygen in this photochemical reaction was also established by the addition of sodium azide. The TiO2 nanophotocatalyst efficiently degrade the didanosine and rose bengal in the presence of the UV light. In the TiO2-induced photocatalytic degradation of didanosine and dyes, the hydroxyl and superoxide radical anion play a prominent role. The finding of this manuscript is very useful to develop an efficient low-cost method for the treatment of wastewater contaminated by antiviral drugs, similar pharmaceutical products and dyes. This study was also very helpful to establish a plausible mechanism behind the phototoxicity of the didanosine.

Interferência da azida de sódio no desenvolvimento de Caenorhabditis elegans (Nematoda: Caenorhabditis)

The nematode Caernohabditis elegans (Maupas, 1900) is an alternative laboratory model animal, widely used in laboratories, because this worm shares around 42% of orthologous genes with humans, has its entire genome sequence encoded and is not a parasite. For this reason, C. elegans was the model chosen for the laboratory's line of research and for our project, in order to investigate the interference of sodium azide in its biological development. NaN3 is a white crystalline solid inorganic compound that is highly toxic and lethal in small quantities. Its mechanism of action is the inhibition of cytochrome C oxidase. Its practical effect on C. elegans is temporary and dose-dependent anesthesia. For our project, the experiment was carried out with different groups, one containing animals of all stages and the other Dauer larvae. Two culture media were used (solid and liquid) and three experimental conditions were used: an overdose of 1M NaN3 and a sub-dose of 1mM NaN3. The observations of both groups were analyzed at 20 min, 1h, 3h, 5h and 24h, totaling five readings taken in triplicate. As a result, NaN3 interfered in the motility of C. elegans, in the biological cycle and changed the appearance of the worm's cuticle. However, the group of larvae submitted to 1mM NaN3 in liquid medium showed better resistance. For this factor, it was discussed that the proteins UPRmt, Hps70, Hps16, gmap-1 and mtROS are possibly involved in the cytoprotection process during exposure of the nematode to NaN3 in both experiments.

O nematoide Caernohabditis elegans (Maupas, 1900) é um animal modelo de laboratório alternativo, muito utilizado nos laboratórios, pois esse verme compartilha cerca de 42% de genes ortólogos com os seres humanos, tem a sequência de seu genoma todo codificado e não são parasitas. Por isso, C. elegans foi o modelo escolhido para a linha de pesquisa do laboratório e para o nosso projeto, de modo a investigar a interferência da azida de sódio em seu desenvolvimento biológico. A NaN3 é um é um composto inorgânico sólido cristalino branco altamente tóxico e letal em pequenas quantidades. Seu mecanismo de ação é a inibição do citocromo C oxidase. O seu efeito prático em C. elegans é de anestesia temporária e dose dependente. Para nosso projeto o experimento foi realizado com grupos distintos, sendo que um continha animais de todas as fases e o outro as larvas Dauer. Foram empregados dois meios de cultura (sólido e o líquido) e três condições experimentais, sendo uma superdosagem de NaN3 a 1M e uma sub dose de NaN3 a 1mM. As observações de ambos os grupos foram analisadas em 20 min, 1h, 3h, 5h e 24h, totalizando cinco leituras feitas em triplicata. Como resultado a NaN3 interferiu na motilidade dos C. elegans, no ciclo biológico e mudou o aspecto da cutícula do verme, no enteando, o grupo de larvas submetidas a NaN3 a 1mM no meio líquido, apresentaram melhor resistência. Para esse fator, foi-se discutido que as proteínas UPRmt, Hps70, Hps16, a gmap-1 e mtROS estão possívelmente envolvidas no processo de citoproteção durante a expsição do nematoide a NaN3 em ambos os experimentos.

Internet-Purchased Sodium Azide Used in a Fatal Suicide Attempt: A Case Report and Review of the Literature.

There has been a significant increase in sodium azide intoxications since the 1980s. Intoxications caused by sodium azide are becoming increasingly prevalent in the Netherlands as a result of its promotion for the purpose of self-euthanasia. The mechanism of toxicity is not completely understood but is dose-dependent. The presented case describes a suicide by sodium azide of a young woman (26 years old) with a history of depression and suicide attempts. The decedent was found in the presence of prescription medicine, including temazepam, domperidone in combination with omeprazole, and the chemical preservative sodium azide. Quantitative toxicology screening of whole blood revealed the presence of 70 µg/L temazepam (toxic range > 1000 µg/L) and 28 mg/L sodium azide (fatal range: 2.6-262 mg/L). Whole blood qualitative analysis revealed the presence of temazepam, temazepam-glucuronide, olanzapine, n-desmethylolanzapine, and acetaminophen. In circles promoting sodium azide, it is recommended to use sodium azide in combination with medications targeting sodium azide's negative effects, such as analgesics, antiemetics, and anti-anxiety drugs. The medicines recovered at the body's location, as well as the results of the toxicology screens, were consistent with the recommendations of self-euthanasia using sodium azide.

Clinical features of COVID-19 rapid antigen test exposures reported by an Australian poisons information centre: a prospective study.

INTRODUCTION: Coronavirus disease COVID-19 rapid antigen tests are a useful tool in detecting infection, and their use has increased in many countries since they became commercially available in late 2021. Some rapid antigen tests contain sodium azide, which can be toxic in small doses. This study aimed to describe the clinical characteristics of exposures to COVID-19 rapid antigen tests. METHODS: This is a prospective study conducted by the New South Wales Poisons Information Centre. From 22 January 2022 to 31 August 2022, rapid antigen test exposures were followed up to obtain outcome information. Data collected included: brand/ingredients, exposure route, demographics, symptoms, and disposition. RESULTS: We recorded 218 exposures in the seven-month study period. Complete follow-up information was available in 75% (n = 164). There were 53 exposures to sodium azide-containing products (35 with follow-up data) and 165 to non-sodium azide-containing products and unknown ingredient exposures (129 with follow-up data). Overall, unintentional exposures predominated (n = 182), and 151 were ingestions. The vast majority (>90%) did not develop symptoms, and all symptoms that developed were mild. Most cases (95%, n = 208) did not require referral to a healthcare facility. CONCLUSIONS: In this prospective series, few patients developed symptoms, regardless of the sodium azide content, likely due to low concentration and low volume within the test kits. However, ongoing toxicovigilance is warranted.

The vitamin B12 analog cobinamide ameliorates azide toxicity in cells, Drosophila melanogaster, and mice.

CONTEXT: The azide anion (N3-) is highly toxic. It exists most commonly as sodium azide, which is used widely and is readily available, raising the potential for occupational incidents and use as a weapon of mass destruction. Azide-poisoned patients present with vomiting, seizures, hypotension, metabolic acidosis, and coma; death can occur. No specific azide antidote exists, with treatment being solely supportive. Azide inhibits mitochondrial cytochrome c oxidase and is likely oxidized to nitric oxide in vivo. Cytochrome c oxidase inhibition depletes intracellular adenosine triphosphate and increases oxidative stress, while increased nitric oxide causes hypotension and exacerbates oxidative damage. Here, we tested whether the cobalamin (vitamin B12) analog cobinamide, a strong and versatile antioxidant that also neutralizes nitric oxide, can reverse azide toxicity in mammalian cells, Drosophila melanogaster, and mice. RESULTS: We found cobinamide bound azide with a moderate affinity (Ka 2.87 × 105 M-1). Yet, cobinamide improved growth, increased intracellular adenosine triphosphate, and reduced apoptosis and malondialdehyde, a marker of oxidative stress, in azide-exposed cells. Cobinamide rescued Drosophila melanogaster and mice from lethal exposure to azide and was more effective than hydroxocobalamin. Azide likely generated nitric oxide in the mice, as evidenced by increased serum nitrite and nitrate, and reduced blood pressure and peripheral body temperature in the animals; the reduced temperature was likely due to reflex vasoconstriction in response to the hypotension. Cobinamide improved recovery of both blood pressure and body temperature. CONCLUSION: We conclude cobinamide likely acted by neutralizing both oxidative stress and nitric oxide, and that it should be given further consideration as an azide antidote.

Ceruloplasmin Interferes with the Assessment of Blood Lipid Hydroperoxide Content in Small Ruminants.

Simple and inexpensive analytical methods for assessing redox balance in biological matrixes are widely used in animal and human diagnostics. Two of them, reactive oxygen metabolites (ROMs) and total oxidant status (TOS), evaluate the lipid hydroperoxide (LOOH) content of the sample and are based on iron-mediated mechanisms. However, these tests provide uncorrelated results. In this study, we compared these two tests in the blood serum of goat kids and lambs, together with an evaluation of ceruloplasmin (CP) oxidase activity. No significant correlation was found between ROMs and TOS, or between TOS and CP oxidase activity, in either species. Conversely, ROMs and CP oxidase activity were highly correlated in both kid and lamb samples (p < 0.001). A significant progressive reduction in the analytical signal in the ROMs assay was observed when sodium azide, an effective CP inhibitor, was added to the samples before the assay (p < 0.001). This decrease was related to sodium azide concentration (p < 0.01) and was not found when sodium azide was added at the same concentrations in the TOS assay. These findings suggest that ROMs, unlike TOS, may be affected by CP, which interferes with LOOH detection in blood samples.

Olive juice dry extract containing hydroxytyrosol, as a nontoxic and safe substance: Results from pre-clinical studies and review of toxicological studies.

Products derived from olives, such as the raw fruit and oils, are widely consumed due to their taste, and purported nutritional/health benefits. Phenolic compounds, especially hydroxytyrosol (HT), have been proposed as one of the key substances involved in these effects. An olive juice extract, standardized to contain 20% HT ("OE20HT"), was produced to investigate its health benefits. The aim of this study was to demonstrate the genotoxic safety of this ingredient based on in vitro Ames assay and in vitro micronucleus assay. Results indicated that OE20HT was not mutagenic at concentrations of up to 5000 µg/plate, with or without metabolic activation, and was neither aneugenic nor clastogenic after 3-hour exposure at concentrations of up to 60 µg/mL with or without metabolic activation, or after 24-hour exposure at concentrations of up to 40 µg/mL. To further substantiate the safety of OE20HT following ingestion without conducting additional animal studies, a comprehensive literature review was conducted. No safety concerns were identified based on acute or sub-chronic studies in animals, including reproductive and developmental studies. These results were supported by clinical studies demonstrating the absence of adverse effects after oral supplementation with olive extracts or HT. Based on in vitro data and the literature review, the OE20HT extract is therefore considered as safe for human consumption at doses up to 2.5 mg/kg body weight/day.

Treatment of seeds with sodium azide for quantitative and qualitative capsule traits at M2 generation of Fourteen Ethiopian sesame (Sesamum indicum L.) genotypes.

This study aimed at investigating the effects of sodium azide (NaN3) on quantitative and qualitative capsule traits in M2 generation of 14 Ethiopian sesame genotypes collected from Humera Agricultural Research Center (HuARC), Tigrai. Both the treatment and control seeds were sown in well-prepared beds in greenhouse to develop M2 plants. Data on quantitative and qualitative traits were collected and analyzed using GenStat 16 software. Results showed significant differences among the M2 seeds treated with 0.75% NaN3. The highest mean number of capsules per plant was recorded in ACC44 and Baha Necho genotypes, while the lowest was recorded in Gumero, Setit 2, Hirhir, ADI, Bounji and Aberghele. The highest mean number of seeds per capsule was recorded in Humera 1, Baha Necho, Zeri Tesfay, and Gondar 1 genotypes and the lowest was recorded in Setit 1, Setit 2 and ADI. The highest mean capsule length was observed in Zeri Tesfay while the lowest was recorded in Aberghele. The qualitative data reported that Hirhir, Setit 1 and Setit 2 were changed from completely shattering to partially shattering, Gumero and Bounji were changed from completely shattering to non-shattering, and Zeri Tesfay was changed from partially shattering to non-shattering. The 14 genotypes were clustered into four distinct groups including cluster I containing six genotypes, cluster II and III containing two genotypes each and cluster IV containing four genotypes. The mutants developed from Zeri Tesafy, ACC44 and Baha Necho genotypes are considered as potential candidate mutants for further utilization in sesame improvement.

Acid-Switchable Synthesis of Trifluoromethylated Triazoles and Isoxazoles via Reaction of CF3-Ynones with NaN3: DFT Study of the Reaction Mechanism.

A detailed study of the reaction of CF3-ynones with NaN3 was performed. It was found that the reaction permits the selective synthesis of either 4-trifluoroacetyltriazoles or 5-CF3-isoxazoles. The chemoselectivity of the reaction was switchable via acid catalysis. The reaction of CF3-ynones with NaN3 in EtOH produced high yields of 4-trifluoroacetyltriazoles. In contrast, the formation of 5-CF3-isoxazoles was observed under catalysis by acids. This acid-switchable procedure can be performed at sub-gram scale. The possible reaction mechanism was supported by DFT calculations. The synthetic utility of the prepared 4-trifluoroacetyltriazoles was demonstrated.

Generating better leaf traits in M2 lines of fourteen Ethiopian sesame (Sesamum indicum L.) genotypes through the treatment of their seeds with sodium azide.

The present study explored the effect of sodium azide (NaN3) on quantitative and qualitative leaf traits of M2 lines on 14 Ethiopian sesame genotypes collected from Humera Agricultural Research Center, Tigrai, Ethiopia. Qualitative data on leaf color, leaf hairiness, leaf arrangement, leaf shape, basal leaf profile, basal leaf margin, and leaf angle to main stem as well as quantitative data on length of basal leaf, length of top leaf, width of basal leaf, width of top leaf, length of marginal leaf, and width of marginal leaf were recorded and analyzed using analysis of variance, clustering analysis, Mahalanobis distance, and principal component analysis. Generally, treatment of seeds with NaN3 has brought many distinct and statistically significant phenotypic changes on both quantitative and qualitative leaf traits of the M2 lines. The changes in the NaN3 treated and locally adapted genotypes of Gumero and Zeri Tesfay are promising; producing the highest mean length of basal leaf (p ≤ 0.01). NaN3 treated seeds of Baha Necho, Gumero, and Hirhir developed the highest mean width of basal leaf. Locally adapted genotypes have responded positively to NaN3 treatment, generating better leaf traits as compared to the research improved ones. This study was the first of its kind in exploring the effects of NaN3 seed treatment on leaf traits of sesame genotypes. The findings of this study will, therefore, serve as a steppingstone to look into the effects of the changes in sesame yield and initiate future genetic and molecular studies on the responsive genotypes.

Ethyl Methane Sulfonate and Sodium Azide-Mediated Chemical and X-ray-Mediated Physical Mutagenesis Positively Regulate Peroxidase 1 Gene Activity and Biosynthesis of Antineoplastic Vinblastine in Catharanthus roseus.

Catharanthus roseus synthesizes bioactive therapeutic metabolites, known as monoterpenoid indole alkaloids (MIAs), including antineoplastic vinblastine and vincristine, which have high global demand, and antihypertensive ajmalicine, a serpentine. However, the in planta biosynthesis and accumulation of these phytopharmaceuticals are very low, attributed to their high cytotoxicity in the plant. Considering the low in planta concentration and over-harvesting of plant resources, biotechnological interventions have been undertaken to enhance the production of MIAs in plant systems. The present study was carried out to mutation through chemical and physical mutagenesis with sodium azide, ethyl methane sulfonate and X-rays, respectively, on C. roseus to determine their possible effects on the transcriptional modulation of MIA biosynthetic pathways in planta. The chemical mutagenesis resulted in delayed seed pod development in mutated C. roseus plants, with distinct leaf morphology and flower color. However, X-ray mutagenesis resulted in pollen-less sterile flowers. An HPLC analysis confirmed the higher catharanthine, vindoline and vinblastine content in sodium azide and X-ray mutants, and was further supported by higher PRX1 transcript levels estimated through real-time PCR analysis. The transcription factors WRKY1 and ORCA2 were found negatively regulated along with major MIA pathway genes in chemical mutants and their M1 generation, but showed positive regulation in X-ray M0 mutants. The induced mutagenesis of C. roseus provides a prospective strategy to modulate plant transcriptomes and enhance the biosynthesis of pharmaceutically important antineoplastic vinblastine in the plant.

Improvement of German Chamomile (Matricaria recutita L.) for Mechanical Harvesting, High Flower Yield and Essential Oil Content Using Physical and Chemical Mutagenesis.

Chamomile (Matricariarecutita L.) is one of the most important medicinal plants with various applications. The flowers and flower heads are the main organs inthe production of essential oil. The essential improvement goals of chamomile are considered to be high flower yield and oil content, as well asthe suitability for mechanical harvesting. The present study aimed to improve the flower yield, oil content and mechanical harvestability of German chamomile via chemical and physical mutagens. Three German chamomile populations (Fayum, Benysuif and Menia) were irradiated with 100, 200, 300 and 400 Gray doses of gamma rays, as well as chemically mutagenized using 0.001, 0.002 and 0.003 mol/mL of sodium azide for 4 h. The two mutagens produced a wide range of changes in the flowers' shape and size. At M3 generation, 18 mutants (11 from gamma irradiation and 7 from sodium azide mutagenization) were selected and morphologically characterized. Five out of eighteen mutants were selected for morphological and chemical characterization for oil content, oil composition and oil quality in M4 generation. Two promising mutants, F/LF5-2-1 and B/HNOF 8-4-2, were selected based on their performance in most studied traits during three generations, as well as the high percentage of cut efficiency and a homogenous flower horizon, which qualify them as suitable candidates for mechanical harvesting. The two mutants are late flowering elite mutants; the F/LF5-2-1 mutant possessed the highest oil content (1.77%) and number of flowers/plant (1595), while the second promising B/HNOF 8-4-2 mutant hada high oil content (1.29%) and chamazulene percentage (13.98%) compared to control plants. These results suggest that the B/HNOF 8-4-2 and F/LF5-2-1 mutants could be integrated as potential parents into breeding programs for a high number of flowers, high oil content, oil composition and oil color traits for German chamomile improvement.

Effect of Sodium Azide on Yield and its Components in Bread Wheat (Triticum aestivum L.).

<b>Background and Objective:</b> The wheat crop is considered one of the most important crops globally, especially in Egypt. It has great nutritional importance, so it was necessary to increase productivity and any genetic improvement depends on the presence of many genetic differences so that breeders can achieve this. This study aimed to use chemical mutagenic (sodium azide) to obtain the desired genetic differences in two wheat cultivars. <b>Materials and Methods:</b> Two types of bread Sids 12 and Giza 164 were treated with different concentrations of sodium azide (NaN₃) (1000, 2000, 3000, 4000, 5000 and 6000 ppm). <b>Results:</b> The highest grain/plant 78.91 g was obtained from Sis12 and 62.96 g from Giza 164 compared to the control 42.57 and 40.24 g for Sids 12 and Giza 164, respectively. Also from the results obtained, the relationship of yield was positive and significant with both grain/spike, spikelet's no./spike spikes no./plant and height/plant. On the contrary, it was negative and significant with a 1000-grain weight (-0.433). <b>Conclusion:</b> The two treatments (1000 and 2000 ppm) were the best in the Sids 12, while (1000 and 5000 ppm) were the best treatments in the Giza 164.

Mutagenic effects of sodium azide on in vitro mutagenesis, polymorphism and genomic instability in wheat (Triticum aestivum L.).

INTRODUCTION: Breeding studies are commonly conducted to develop new cultivars with high yield levels and improved quality traits. Chemically-induced mutations are used to create genetic variations in wheat genomes. Various physical and chemical mutagens are used to increase frequency of mutations and facilitate the selection processes. Sodium azide (SA) is largely employed to induce mutations of the genes regulating essential traits. Such mutations may also elucidate gene functions of the mutant phenotypes. Present experiments were conducted to investigate potential use of conventional chemical mutagenesis technique through SA for mature embryo culture in wheat. METHODS AND RESULTS: Sodium azide mutagenesis was experimented with 4 treatment durations (1, 2, 3 and 4 h) and 5 treatment concentrations (0, 1, 2, 3 and 4 mM). Mature embryos were subjected to experimental treatments to detect optimum doses of mutagenesis and to estimate polymorphism and genomic instability. Primarily, 50% reduction in number of regenerated plants as compared to the control (LD50) was adopted as the optimum dose. Based on LD50 criterion, the optimum value was achieved at 1 h duration of 4 mM SA concentration. Afterwards, inter-primer binding site markers were applied to investigate polymorphism and genomic instability in the regenerated plants. CONCLUSIONS: Present findings revealed that efficiency of chemical mutagenesis could be improved through the use of molecular technology and such mutations may assist plant breeders in developing high-yield cultivars.

Chemical Composition, In Silico and In Vitro Antimutagenic Activities of Ethanolic and Aqueous Extracts of Tigernut (Cyperus esculentus).

Tigernut, also known as Cyperus esculentus, is said to be high in nutritional and medicinal value. The purpose of this study was to determine the C. esculentus's antimutagenic activity. The ethanolic and aqueous extracts of the nut were analyzed for chemical constituents, antioxidants, ultraviolet-visible, and gas chromatography-mass spectrometry using standard procedures. The extracts contained a total of 17 major compounds that were docked against human RecQ-like protein 5 (RECQL5) helicase protein. The antimutagenic property of the ethanolic extract in vitro was assessed using the Allium cepa chromosome assay. Onion bulbs were pre-treated with 200 mg/kg of ethanolic extract of C. esculentus for 24 h and then, grown in NaN3 (250 µg/L) for 24 h; onion bulbs were also first exposed to NaN3 (250 µg/L) for 24 h before treatment with 100 mg/kg and 200 mg/kg of the ethanolic extract respectively. Standard methods were used to determine the mitotic index and chromosomal aberrations. Results revealed that C. esculentus ethanolic extract contained flavonoids (22.47 mg/g), tannins (0.08 mg/g), alkaloids (19.71 mg/g), glycosides, phenol, and tannin and showed high scavenging activity against 2,2-diphenyl-1-picrylhydrazyland H2O2. Docking with RECQL5 showed good binding energies (∆G>-7) of five compounds in C. esculentus ethanolic extract. The A. cepa assay results revealed a significant (P<0.05) reduction in chromosomal aberrations and a higher mitotic index in groups treated with the C. esculentus ethanolic extract. The antimutagenic activity of C. esculentus ethanolic extract was attributed to its high levels of phytosterols and phenolic compounds.

Mitochondrial Inhibition by Sodium Azide Induces Assembly of eIF2α Phosphorylation-Independent Stress Granules in Mammalian Cells.

Mitochondrial stress is involved in many pathological conditions and triggers the integrated stress response (ISR). The ISR is initiated by phosphorylation of the eukaryotic translation initiation factor (eIF) 2α and results in global inhibition of protein synthesis, while the production of specific proteins important for the stress response and recovery is favored. The stalled translation preinitiation complexes phase-separate together with local RNA binding proteins into cytoplasmic stress granules (SG), which are important for regulation of cell signaling and survival under stress conditions. Here we found that mitochondrial inhibition by sodium azide (NaN3) in mammalian cells leads to translational inhibition and formation of SGs, as previously shown in yeast. Although mammalian NaN3-induced SGs are very small, they still contain the canonical SG proteins Caprin 1, eIF4A, eIF4E, eIF4G and eIF3B. Similar to FCCP and oligomycine, other mitochodrial stressors that cause SG formation, NaN3-induced SGs are formed by an eIF2α phosphorylation-independent mechanisms. Finally, we discovered that as shown for arsenite (ASN), but unlike FCCP or heatshock stress, Thioredoxin 1 (Trx1) is required for formation of NaN3-induced SGs.