Aminoguanidine Research Articles

FOX-7 based nitrogen rich green energetic salts: Synthesis, characterization, propulsive and detonation performance

New 1,1-diamino-2,2-dinitroethene (FOX-7)-based energetic salts are reported in this study. A variety of bases including hydrazine, hydroxylamine, ammonia, amino guanidine and metal hydroxides (MOH) were found to react with FOX-7 to give the following salts: hydrazinium (E)-2-amino-2-hydrazinylidene-1,1-dinitroethan-1-ide (1) dihydroxylammonium mono((Z)-2-amino-2-(hydroxyimino)-1,1-dinitroethan-1-ide) (2) ammonium (1-amino-2,2-dinitrovinyl)amide (3), potassium/sodium/lithium(I)-[(Z)-2-amino-2-hydrazineylidene-1,1-dinitroethan-1-ide] (4–6), and aminoguanidine-(Z)-2-amino-2-hydrazinylidene-1,1-dinitroethan-1-ide (7). The title compounds were fully characterizedusing IR, NMR, and elemental analysis. The structures of the salts 2 and 7 were further confirmed by single crystal X-ray analysis. These salts have experimental densities in the range between 1.59 gcm−3 to 1.92 g cm−3. Thermal stabilities of these salts were measured by DSC and TGA analysis and their decomposition temperatures were found between 85 °C and 177 °C. Enthalpies of formation (ΔHf°) were calculated (Gaussian 03) and with their experimental densities, the propulsive and detonation properties of the nitrogen-rich green energetic salts were evaluated. These compounds exhibit high density, high positive enthalpy (ΔHf°), balanced nitrogen and oxygen contents with excellent propulsive (Isp) and good detonation properties (DP and DV) which are superior to that of RDX, ammonium perchlorate (AP), and comparable to TKX-50. The energetic salts (1, 2, 5 and 6) show potential as highly promising secondary explosives. These energetic salts have potential as promising solid propellants.

Redox imaging of dextran sodium sulfate-induced colitis mice treated with nitric oxide synthase inhibitors

Ulcerative colitis (UC) is an inflammatory bowel disease of unknown cause. Redox imbalance, as characterized by excessive production of reactive oxygen species (ROS) and nitric oxide (NO), and deficient levels of endogenous antioxidants, is associated with the pathogenesis of UC. Overhauser-enhanced magnetic resonance imaging (OMRI) combined with a spin-probe method produces high-resolution images of redox imbalance in disease states. We aimed to investigate the effect of NO synthase (NOS) inhibitors on colonic ROS generation in mice with colitis induced by dextran sodium sulfate (DSS) using the OMRI/spin-probe method. Symptoms of DSS-induced colitis were ameliorated by an inducible NOS (iNOS) inhibitor, aminoguanidine (AG), but not by a non-selective NOS inhibitor, NG-Nitro-L-arginine methyl ester (L-NAME). Intracellular ROS generation, observed as the enhancement of OMRI contrast decay rates of a 3-methoxy-2,2,5,5-tetramethylpyrrolidine-1-oxyl probe in the colons of DSS-induced colitis mice, was suppressed by AG, in agreement with the results of an in vivo electron spin resonance study. AG had an inhibitory effect on ROS production at the upper colon and rectum during the initiation stage of colitis, and at the upper and lower colon during the advanced stage. Additionally, there were partial differences in the localization of iNOS protein and nitrite/nitrate levels. L-NAME treatment showed a tendency for increased ROS generation at the upper colon during the advanced stage. The OMRI/spin-probe method provides a novel tool for screening ROS inhibitory activity in vivo in DSS-induced colitis mice.

Antioxidant activity and antidiabetic activities of Northern Thai indigenous edible plant extracts and their phytochemical constituents

Diabetes mellitus is the most common non-infective disease characterized by hyperglycemia (high level of blood glucose). Formation of advanced glycation end products (AGEs) in long termed-hyperglycemia and oxidative stress are the key factors to accelerate diabetic complications. To screen potential candidates for treating diabetes, total phenolic content, total flavonoid content, antioxidant activity from crude extracts of some Thai edible plants were primarily assessed, and the inhibiting potential of diabetes and its complications provided from some of these plants were evaluated in terms of their inhibitory activities of α-amylase, α-glycosidase, and AGEs formation. The highest amounts of phenolic and flavonoid compounds were found in the ethanolic extract of Caesalpinia mimosoides (S20, 12.63 ± 1.70 mg GAE/g DW) and Glochidion hirsutum (S8, 3.02 ± 0.25 mg CE/g DW), respectively. The highest antioxidant activity was found in Schinus terebinthifolius Raddi (S26, 217.94 ± 32.30 μg AAE/g DW) whereas the highest inhibitory activities of α-amylase and α-glycosidase were obtained from Basella alba L. (S11, IC50 = 0.21 ± 0.01 mg/ml) and S. terebinthifolius (S26, IC50 = 0.05 ± 0.02 mg/ml) respectively. The inhibitory effects of AGEs formation were studied in vitro using two model systems: BSA-glucose and BSA-methylglycoxal (MGO). The extracts of Glochidion hirsutum (Roxb.) Voigt (S8, IC50 = 0.20 ± 0.01 mg/ml) and Polygonum odoratum Lour. (S13, IC50 = 0.03 ± 0.01 mg/ml) exhibited the inhibitory activity of AGEs formation derived from glucose (BSA-glucose system) stronger than aminoguanidine (AG) (0.26 ± 0.00 mg/ml), which is a common AGEs formation inhibitory drug. By BSA-MGO assay, the inhibition of some selected extracts in this study (G. hirsutum, G. sphaerogynum, and S. terebinthifolius with IC50 = 0.11 ± 0.01, 0.11 ± 0.01, and 0.10 ± 0.00 mg/ml, respectively) were slightly less efficient than AG (the IC50 = 0.06 ± 0.00 mg/ml). These results indicated that some selected Thai edible plants in this present study provided potential applications towards the prevention of diabetes and their complications via the inhibitory of α-amylase, α-glycosidase, AGEs formation, and oxidative stress. This fundamental information would be important for alternative drug discovery and nutritional recommendations for diabetic patients.

Anti-glycation level of pectic oligosaccharide in orange peel and its stability in accelerated storage temperature

In this study, pectic oligosaccharides of orange peel (OPOs) were isolated and their structure characterized, and then screened according to anti-glycation level compared with aminoguanidine (AG). The results indicated that OPOs mainly included two components, and the main component has more than 50 % inhibition level for the seven glycation products at 60 °C for 40 h. At the accelerated storage temperature, OPOs demonstrated a better anti-glycation level than AG, and this inhibition was concentration-dependent. In addition, the main component in OPOs was separated into 10 fractions by DEAE Sephadex A-25 gel chromatography, the group of 5–7 monosaccharide polymerization showed the best anti-glycation effect, average anti-glycation capability on six products was over 70 % in the 40th hour. The anti-glycation level of this group was closely related to its high content of GalA and molar ratio of GalA: Rha, and positively correlated with time at moderate temperature.

Selective recovery of rhenium from the simulating leaching solutions of uranium ore by amino guanidine functionalized microcrystalline cellulose microsphere

Rhenium (Re) is the rarest metallic element. Re recovery from leaching solution of uranium ore can not only expand the Re resource, but also improve the mining value of uranium ore. In this paper, amino guanidine functionalized cellulose (AGfC) was successfully synthesized and employed as material for effective and selective separation of Re. The adsorption behavior of AGfC toward Re was systematically investigated with batch and fix-bed column experiments. The results demonstrated that the adsorption kinetics were followed by the pseudo-second-order kinetic model. The adsorption isotherm was followed by the Langmuir model, which calculated a maximum adsorption capacity of 264.55 mg/g at pH 2.37. The fix-bed column tests revealed that the Thomas model and Yoon-Nelson model can best describe the column adsorption data. Especially, AGfC can effectively and selectively separate trace ReO4– from the simulated underground leaching solutions of uranium ore. Furthermore, AGfC can be effectively regenerated by HCl or HNO3. FTIR and XPS analyses showed that the adsorption mechanism of ReO4– was the hydrogen bond and the electrostatic interaction by the positive charge of AGfC.

Verification of Bound Aminoguanidine as the Marker Residue for the Banned Antibiotic, Nitrovin, in Pig Tissues.

Nitrovin (NTV) belongs to a class of antibiotics called nitrofurans, which are classified as nonallowed pharmacologically active substances that do not have a maximum residue limit listed in EU legislation. The objectives of this study were to confirm aminoguanidine (AGN) as a suitable marker residue to monitor NTV abuse and to investigate its persistence in porcine tissues. In this work, pigs were fed with NTV-medicated feed (50 mg/kg), and tissues (kidney, muscle, and liver) and plasma were collected on different withdrawal days. All samples were analyzed for bound AGN, total AGN, and the parent drug NTV itself. The highest concentrations of AGN residues were found in the liver, while the lowest were in muscle. Parent NTV was only detected in the kidney at low levels on day 0 of withdrawal. The findings are in support of using AGN as the marker residue for monitoring the illegal use of NTV in animal-derived products.

Pyridoxamine and Aminoguanidine Attenuate the Abnormal Aggregation of β-Tubulin and Suppression of Neurite Outgrowth by Glyceraldehyde-Derived Toxic Advanced Glycation End-Products.

Diabetes mellitus (DM) has been identified as a risk factor for the onset and progression of Alzheimer’s disease (AD). In our previous study, we demonstrated that glyceraldehyde (GA)-derived toxic advanced glycation end-products (toxic AGEs, TAGE) induced similar alterations to those observed in AD. GA induced dysfunctional neurite outgrowth via TAGE-β-tubulin aggregation, which resulted in the TAGE-dependent abnormal aggregation of β-tubulin and tau phosphorylation in human neuroblastoma SH-SY5Y cells. However, the effects of inhibitors of AGE formation on dysfunctional neurite outgrowth caused by GA-induced abnormalities in the aggregation of β-tubulin and tau phosphorylation remain unknown. Aminoguanidine (AG), an AGE inhibitor, and pyridoxamine (PM), a natural form of vitamin B6 (VB6), are effective AGE inhibitors. Therefore, the present study investigated whether AG or PM ameliorate TAGE-β-tubulin aggregation and the suppression of neurite outgrowth by GA. The results obtained showed that AG and PM inhibited the formation of TAGE-β-tubulin, mitigated the GA-induced suppression of neurite outgrowth, and reduced GA-mediated increases in tau phosphorylation levels. Collectively, these results suggest the potential of AG and PM to prevent the DM-associated onset and progression of AD.

Glycolaldehyde, an Advanced Glycation End Products Precursor, Induces Apoptosis via ROS-Mediated Mitochondrial Dysfunction in Renal Mesangial Cells.

Glycolaldehyde (GA) is a reducing sugar and a precursor of advanced glycation end products (AGEs). The role of precursor and precursor-derived AGEs in diabetes and its complications have been actively discussed in the literature. This study aimed to elucidate the mechanism of GA-induced apoptosis in renal cells. Immunoblotting results showed that GA (100 μM) caused cytotoxicity in murine renal glomerular mesangial cells (SV40 MES 13) and induced apoptosis via major modulators, decreasing Bcl-2 and increasing Bax, cytochrome c, and cleaved caspase-3/-9 expression. GA-derived AGE accumulation and receptor for AGE (RAGE) expression increased in mesangial cells; however, cells that were cotreated with aminoguanidine (AG) showed no increase in GA-derived AGE concentration. Furthermore, reactive oxygen species (ROS) production was increased by GA, while AG inhibited AGE formation, leading to a decrease in ROS levels in mesangial cells. We evaluated apoptosis through fluorescence-activated cell sorting, and used TUNEL staining to study DNA fragmentation. Additionally, we measured ATP generation and used MitoTracker staining to access changes in mitochondrial membrane potential. This study showed that GA increased AGE concentration, RAGE expression, and excessive ROS generation, leading to renal mesangial cell damage via GA-induced apoptosis pathway caused by mitochondrial dysfunction.

Advanced Glycation End Product Blocker Drugs Have a Great Potential to Prevent Diabetic Cardiomyopathy in an Animal Model of Diabetes Mellitus Type-2.

Introduction Sphingosine 1 phosphate (S1P) is a product of the sphingosine kinase 1 (SphK1) enzyme. Increased S1P can lead to tissue fibrosis that is also one of the pathways for developing diabetic cardiomyopathy. Advanced glycation end products (AGEs) increase S1P in cells. The study is aimed at using aminoguanidine (AG) as an AGEs blocker drug to prevent diabetic cardiomyopathy. Materials and methods. 210 rats were enrolled in the study. Diabetes mellitus type-2 was induced, and rats were divided into AG treated diabetic and nondiabetic groups. The heart histology was assessed with Masson's trichrome and hematoxylin-eosin staining. Cardiac function was measured with transthoracic echocardiography. S1P level and SphK1 gene expression were measured by western-blot and RT-qPCR, respectively. Results Results showed that S1P level increases in diabetes, and its augmentation in cardiac tissue with K6PC-5 leads to cardiac fibrosis. 50 and 200 mg/kg of AG prevented cardiac fibrosis, but 100 mg/kg had no significant preventive effect. AG suppressed the SphK1 gene expression and reduced the fibrotic effect of S1P. AG preserved cardiac function by keeping ejection fraction and fractional shortening within the normal range in diabetic rats. Conclusion AG has a suppressor effect on SphK1 gene expression besides its AGEs blocker role. AG is a potential drug to use in diabetic patients for preventing the development of diabetic cardiomyopathy. Other drugs that have AGEs or S1P blocker effects are a good choice for diabetic cardiomyopathy prevention.

Methylglyoxal Scavengers Attenuate Angiogenesis Dysfunction Induced by Methylglyoxal and Oxygen-Glucose Deprivation.

Cerebral endothelial cells play an essential role in brain angiogenesis, and their function has been found to be impaired in diabetes. Methylglyoxal (MG) is a highly reactive dicarbonyl metabolite of glucose formed mainly during glycolysis, and its levels can be elevated in hyperglycemic conditions. MG is a potent precursor of AGEs (advanced glycation end-products). In this study, we investigated if MG can induce angiogenesis dysfunction and whether MG scavengers can ameliorate angiogenesis dysfunction induced by MG. Here, we used cultured human brain microvascular endothelial cells (HBMECs) treated with MG and oxygen-glucose deprivation (OGD) to mimic diabetic stroke in vitro. We also used the MG challenged chicken embryo chorioallantoic membrane (CAM) to study angiogenesis in vivo. Interestingly, administration of MG significantly impaired cell proliferation, cell migration, and tube formation and decreased protein expression of angiogenesis-related factors, which was rescued by three different MG scavengers, glyoxalase 1 (GLO1), aminoguanidine (AG), and N-acetyl cysteine (NAC). In cultured CAM, MG exposure significantly reduced angiogenesis and the angiogenesis-related dysfunction could be attenuated by pretreatment with AG or NAC. Treatment of cultured HBMECs with MG plus OGD increased cellular apoptosis significantly, which could be prevented by exposure to GLO1, AG, or NAC. We also noted that administration of MG increased cellular oxidative stress as measured by reactive oxygen species (ROS) generation, enhanced AGE accumulation, and receptor for advanced glycation end-product (RAGE) expression in the cultured HBMECs, which were partially reversed by GLO1, AG, or NAC. Taken together, our findings demonstrated that GLO1, AG, or NAC administration can ameliorate MG-induced angiogenesis dysfunction, and this can be mainly attributed to attenuated ROS production, reduced cellular apoptosis, and increased levels of angiogenic factors. Overall, this study suggested that GLO1, AG, or NAC may be promising candidate compounds for the treatment of angiogenesis dysfunction caused by hyperglycemia in diabetic ischemic stroke.

Attenuation of hyperglycemia and amadori products by aminoguanidine in alloxan-diabetic rabbits occurs via enhancement in antioxidant defenses and control of stress.

The micro- and macro-complications in diabetes mellitus (DM) mainly arise from the damage induced by Amadori and advanced glycation end products, as well as the released free radicals. The primary goal of DM treatment is to reduce the risk of micro- and macro-complications. In this study, we looked at the efficacy of aminoguanidine (AG) to prevent the production of early glycation products in alloxan-diabetic rabbits. Type1 DM was induced in rabbits by a single intravenous injection of alloxan (90 mg/kg body weight). Another group of rabbits was pre-treated with AG (100 mg/kg body weight) prior to alloxan injection; this was followed by weekly treatment with 100 mg/kg of AG for eight weeks. Glucose, insulin, and early glycation products (HbA1C and fructosamine) were measured in control, diabetic and AG treated diabetic rabbits. The effects of hyperglycemia on superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (Gpx), reduced glutathione (rGSH), nitric oxide, lipid peroxides, and protein carbonyl were investigated. Alloxan-diabetic rabbits had lower levels of SOD, CAT, Gpx, and rGSH than control rabbits. Nitric oxide levels were considerably greater. AG administration restored the activities of SOD, CAT, Gpx enzymes up to 70–80% and ameliorated the nitric oxide production. HbA1c and fructosamine levels were considerably lower in AG-treated diabetic rabbits. The observed control of hyperglycemia and amadori adducts in alloxan-diabetic rabbits by AG may be attributed to decrease of stress and restoration of antioxidant defenses.

In Vitro and In Vivo Antiglycation Effects of Connarus ruber Extract.

Accumulation of advanced glycation end products (AGEs) of the Maillard reaction has been implicated in the pathogenesis of diabetes and its complications. Connarus ruber has been used as a folk remedy for several diseases, including diabetes; however, its underlying mechanism has not yet been investigated. This study investigated the effects of C. ruber extract against glycation on collagen-linked AGEs in vitro and streptozotocin-induced diabetic rats (STZ-DM rats) in vivo. The antiglycation activities of C. ruber extract and aminoguanidine (AG) were examined using a collagen glycation assay kit. Nonfluorescent AGE, Nε-carboxymethyl lysine (CML), Nω-carboxymethyl arginine, and Nε-carboxyethyl lysine levels were measured via electrospray ionization-liquid chromatography-tandem mass spectrometry. The effect of the extract on the cytotoxicity of methylglyoxal (MG), a precursor of AGEs, was examined in HL60 cells. STZ-DM rats were treated with the extract for 4 wk, and the effect was assessed using biochemical markers in the serum and CML-positive cells in renal tissues. C. ruber extract dose-dependently inhibited the glycation of collagen and formation of nonfluorescent AGEs, which was comparable to AG, and it significantly attenuated MG-induced cytotoxicity in HL60 cells. Furthermore, the glycated albumin levels in STZ-DM rats decreased, the increase in serum lipid levels was reversed, and immunohistochemistry demonstrated that CML deposition in the glomerulus of STZ-DM rats significantly decreased. Although further studies are needed, C. ruber could be a potential therapeutic for preventing and progressing many pathological conditions, including diabetes.

Green synthesis, characterization, biological evaluation and docking study of some pyrazoline and pyrimidine derivatives

Green and classical techniques have been utilized for preparing of a variety of aryl - substituted pyrazoline and pyrimidine derivatives (2-8). Reactions of chalcones 1 with semicarbazide and thiosemicarbazide, nicotinic acid hydrazide and amino guanidine hydrochloride afforded the corresponding N-substituted pyrazoline derivatives 2-5. Pyrimidine derivatives 6-8 were achieved via reaction of chalcone derivatives 1 with several reagents namely: guanidine nitrate, thiourea and 6-amino-2-thioxo-2,3- dihydropyrimidin-4(1H)-one under conventional and ultrasonic conditions. Ultrasonic method was found to be an easy work-up procedure and it gave high yield in comparison with conventional method. The structures of new synthesis compounds were characterized by elemental and spectral analyses. Some of newly compounds were tested in vitro antibacterial activity against some gram–positive and gram–negative. The antimicrobial results displayed favorable antimicrobial activity. Molecular docking has been perfomed for compound 5b using MOE 2008.10, The data results obtained are quite promising.

Aminoguanidine Prevents the Oxidative Stress, Inhibiting Elements of Inflammation, Endothelial Activation, Mesenchymal Markers, and Confers a Renoprotective Effect in Renal Ischemia and Reperfusion Injury

Oxidative stress produces macromolecules dysfunction and cellular damage. Renal ischemia-reperfusion injury (IRI) induces oxidative stress, inflammation, epithelium and endothelium damage, and cessation of renal function. The IRI is an inevitable process during kidney transplantation. Preliminary studies suggest that aminoguanidine (AG) is an antioxidant compound. In this study, we investigated the antioxidant effects of AG (50 mg/kg, intraperitoneal) and its association with molecular pathways activated by IRI (30 min/48 h) in the kidney. The antioxidant effect of AG was studied measuring GSSH/GSSG ratio, GST activity, lipoperoxidation, iNOS, and Hsp27 levels. In addition, we examined the effect of AG on elements associated with cell survival, inflammation, endothelium, and mesenchymal transition during IRI. AG prevented lipid peroxidation, increased GSH levels, and recovered the GST activity impaired by IRI. AG was associated with inhibition of iNOS, Hsp27, endothelial activation (VE-cadherin, PECAM), mesenchymal markers (vimentin, fascin, and HSP47), and inflammation (IL-1β, IL-6, Foxp3, and IL-10) upregulation. In addition, AG reduced kidney injury (NGAL, clusterin, Arg-2, and TFG-β1) and improved kidney function (glomerular filtration rate) during IRI. In conclusion, we found new evidence of the antioxidant properties of AG as a renoprotective compound during IRI. Therefore, AG is a promising compound to treat the deleterious effect of renal IRI.

Swertiamarin mitigates nephropathy in high-fat diet/streptozotocin-induced diabetic rats by inhibiting the formation of advanced glycation end products

Context The molecular mechanism by which Swertiamarin (SM) prevents advanced glycation end products (AGEs) induced diabetic nephropathy (DN) has never been explored. Objective To evaluate the effect of SM in preventing the progression of DN in high fat diet-streptozotocin-induced diabetic rats. Materials and methods After 1 week of acclimatisation, the rats were divided randomly into five groups as follows: (1) Control group, which received normal chow diet; (2) High-fat diet (HFD) group which was fed diet comprising of 58.7% fat, 27.5% carbohydrate and 14.4% protein); (3) Aminoguanidine (AG) group which received HFD + 100 mg/k.b.w.AG (intraperitoneal); (4) Metformin (Met) group which received HFD + 70 mg/k.b.w. the oral dose of Met and (5) SM group which was supplemented orally with 50 mg/k.b.w.SM along with HFD. After 12 weeks all HFD fed animals were given a single 35 mg/k.b.w. dose of streptozotocin with continuous HFD feeding for additional 18 weeks. Later, various biochemical assays, urine analyses, histopathological analysis of kidneys, levels of AGEs, expression of various makers, and in-silico analysis were performed. Results The diabetic group demonstrated oxidative stress, increased levels of AGEs, decreased renal function, fibrosis in the renal tissue, higher expression of the receptor for advanced glycation end products (RAGE), which were ameliorated in the SM treated group. In-silico analysis suggests that SM can prevent the binding of AGEs with RAGE. Conclusions SM ameliorated DN by inhibiting the oxidative stress induced by AGEs. Highlights SM reduces the levels of hyperglycaemia-induced advanced glycation end products in serum and renal tissue. SM prevents renal fibrosis by inhibiting the EMT in the kidney tissue. The in-silico analysis proves that SM can inhibit the binding of various AGEs with RAGE, thereby inhibiting the AGE-RAGE axis.

Autonomous regulation of inducible nitric oxide synthase and cytochrome P450 2E1-mediated oxidative stress in maneb- and paraquat-treated rat polymorphs

Maneb (MB)- and paraquat (PQ)-induced oxidative stress in rat polymorphonuclear leukocytes (PMNs) is regulated in parallel by cytochrome P450 2E1 (CYP2E1) and inducible nitric oxide synthase (iNOS). However, mechanism underlying their regulation is not yet understood. The study investigated the role of nuclear factor- kappa B (NF-κB) and mitogen-activated protein kinase/extracellular signal regulated kinase/protein kinase C (MEK/ERK/PKC) pathway in the regulation of iNOS- and CYP2E1-induced oxidative stress in PMNs. MB + PQ-induced changes in nitrite content, lipid peroxidation (LPO), iNOS expression/activity and inflammatory mediators were alleviated by aminoguanidine (AG), an iNOS inhibitor, without any change in CYP2E1. Alternatively, diallyl sulphide (DAS), a CYP2E1 inhibitor, rescued from MB + PQ-induced changes in CYP2E1 activity/expression, free radical generation, superoxide dismutase (SOD) activity, LPO and pro-inflammatory cytokines without any alterations in nitrite content and iNOS activity/expression. Pyrrolidine dithiocarbamate (PDTC), NF-κB inhibitor, did not alter CYP2E1 but mitigated free radical generation, SOD activity, LPO, nitrite content, iNOS activity/expression and levels of pro-inflammatory cytokines (tumor necrosis factor-α, interleukine-1β and interleukine-4). Ex-vivo treatment with MEK inhibitor (PD98059), ERK1/2 inhibitor (AG126) or PKC inhibitor (rottlerin) ameliorated MB + PQ-induced increase in free radical generation and CYP2E1 activity/expression in PMNs. While PD98059 and AG126 abated MB + PQ-induced increase in ERK1/2, PKC-α/δ and CYP2E1 levels, rottlerin restored PKC-α/δ and CYP2E1 towards normalcy without affecting ERK1/2 level in MB + PQ-treated group. The results suggest that iNOS and CYP2E1 contributing to MB + PQ-induced oxidative stress in rat PMNs exhibit differential regulatory mechanisms. The inflammatory mediators regulate iNOS expression while CYP2E1 expression is triggered via MEK-ERK1/2-PKC pathway.

High Thermal Stability and Insensitive Fused Triazole-Triazine Trifluoromethyl-Containing Explosives (TFX).

A trifluoromethyl-containing fused triazole-triazine energetic molecule, 3-nitro-7-(trifluoromethyl)-1,2,4-triazolo[5,1-c]-1,2,4-triazin-4-amine (TFX), has been synthesized in three steps from amino guanidine bicarbonate and trifluoroacetic acid. The process was found to be effective, nontoxic, and simple. The X-ray structure analysis of TFX finds that there are inter- and intramolecular hydrogen bonds and π–π interactions in the crystal lattice. TFX with a high density (1.88 g·cm–3) at room temperature, excellent thermal stability (Tp = 300.3 °C), moderate energetic performance, and with insensitivity to mechanical stimulation has potential as heat-resistant energetic materials.

Gold Nanoparticle-Bioconjugated Aminoguanidine Inhibits Glycation Reaction: An In Vivo Study in a Diabetic Animal Model.

Proteins undergo glycation resulting in the generation of advanced glycation end products (AGEs) that play a central role in the onset and advancement of diabetes-associated secondary complications. Aminoguanidine (AG) acts as an antiglycating agent by inhibiting AGE generation by blocking reactive carbonyl species (RCS) like, methylglyoxal (MGO). Previous studies on antiglycating behavior of AG gave promising results in the treatment of diabetes-associated microvascular complications, but it was discontinued as it was found to be toxic at high concentrations (>10 mmol/L). The current article aims at glycation inhibition by conjugating gold nanoparticles (Gnp) with less concentration of AG (0.5-1.0 mmol/L). The HPLC results showed that AG-Gnp fairly hampers the formation of glycation adducts. Moreover, the in vivo studies revealed AG-Gnp mediated inhibition in the production of total-AGEs and -Nε-(carboxymethyl)lysine (CML) in the diabetic rat model. This inhibition was found to be directly correlated with the antioxidant parameters, blood glucose, insulin, and glycosylated hemoglobin levels. Furthermore, the histopathology of AG-Gnp-treated rats showed good recovery in the damaged pancreatic tissue as compared to diabetic rats. We propose that this approach might increase the efficacy of AG at relatively low concentrations to avoid toxicity and might facilitate to overcome the hazardous actions of antiglycating drugs.

Assessing the In Vitro Inhibitory Effects on Key Enzymes Linked to Type-2 Diabetes and Obesity and Protein Glycation by Phenolic Compounds of Lauraceae Plant Species Endemic to the Laurisilva Forest.

Methanolic leaf extracts of four Lauraceae species endemic to Laurisilva forest (Apollonias barbujana, Laurus novocanariensis, Ocotea foetens and Persea indica) were investigated for the first time for their potential to inhibit key enzymes linked to type-2 diabetes (α-amylase, α-glucosidase, aldose reductase) and obesity (pancreatic lipase), and protein glycation. Lauraceae extracts revealed significant inhibitory activities in all assays, altough with different ability between species. In general, P. indica showed the most promissing results. In the protein glycation assay, all analysed extracts displayed a stronger effect than a reference compound: aminoguanidine (AMG). The in vitro anti-diabetic, anti-obesity and anti-glycation activities of analysed extracts showed correlation with their flavonols and flavan-3-ols (in particular, proanthocyanins) contents. These Lauraceae species have the capacity to assist in adjuvant therapy of type-2 diabetes and associated complications, through modulation of the activity of key metabolic enzymes and prevention of advanced glycation end-products (AGEs) formation.

Insights into the effects of inducible and neuronal nitric oxide synthase isoenzymes in experimental intestinal heterophyiasis

Background: Heterophyiasis is one of the food-borne trematode infections, caused by the intestinal flukeHeterophyes heterophyes. The exact role of nitric oxide (NO) in the immune response against the majorityof parasites remains controversial. It proved protective against a wide range of protozoan and helminthicparasites. Nevertheless, its role in intestinal heterophyiasis is yet to be explored.Objectives: The study aims to explore the possible roles of inducible nitric oxide synthase (iNOS) andneuronal nitric oxide synthase (nNOS) in experimental intestinal heterophyiasis.Material and Methods: The experimental study design included infection of male puppies with H.heterophyes encysted metacercariae (EMC), followed by treatment with aminoguanidine (AG) and7-nitroindazole (7-NI) drugs, as selective inhibitors of iNOS and nNOS, respectively. Controls includednon-infected and infected untreated puppies. Intestinal tissue sections from all puppies were stained forhistopathological and immunohistochemical (IHC) assessments.Results: Different intensities of iNOS and nNOS isoenzymes were observed in intestinal sections. The studyshowed the highest concentration of iNOS isoenzyme in the infected-7-NI treated group. The control noninfectedpuppies exhibited the highest levels of nNOS expression, with statistical significance (P<0.05).The study also showed that AG significantly reduced the degree of inflammatory cellular infiltrations.Additionally, the over-production of NO worsened the degree of intestinal apoptotic changes.Conclusion: Results obtained in the study suggested that inhibition of iNOS, to some extent, improvedintestinal architecture, while inhibition of nNOS failed to eliminate experimental intestinal heterophyiasis.