Hydralazine represses Fpn ubiquitination to rescue injured neurons via competitive binding to UBA52

A major impedance to neuronal regeneration after peripheral nerve injury (PNI) is the activation of various programmed cell death mechanisms in the dorsal root ganglion. Ferroptosis is a form of programmed cell death distinguished by imbalance in iron and thiol metabolism, leading to lethal lipid peroxidation. However, the molecular mechanisms of ferroptosis in the context of PNI and nerve regeneration remain unclear. Ferroportin (Fpn), the only known mammalian nonheme iron export protein, plays a pivotal part in inhibiting ferroptosis by maintaining intracellular iron homeostasis. Here, we explored in vitro and in vivo the involvement of Fpn in neuronal ferroptosis. We first delineated that reactive oxygen species at the injury site induces neuronal ferroptosis by increasing intracellular iron via accelerated UBA52-driven ubiquitination and degradation of Fpn, and stimulation of lipid peroxidation. Early administration of the potent arterial vasodilator, hydralazine (HYD), decreases the ubiquitination of Fpn after PNI by binding to UBA52, leading to suppression of neuronal cell death and significant acceleration of axon regeneration and motor function recovery. HYD targeting of ferroptosis is a promising strategy for clinical management of PNI.

Method Verification and Validation of Hydralazine Hydrochloride: Spectrophotometric Analysis in Pure and Pharmaceutical Formulations

The new method proposed is based on the formation of hydralazine-Bromophenol blue ion pair simply and without further extraction or heating. The ion pair was prepared in the presence of pH 3 citrate buffer forming a yellow-colored chromogen. A new maximum UV-visible band formed at 416 nm. The color was stable for more than 10 hours and obeyed Beer’s Law over the concentration range of 10 - 50 µg/mL. The calculated molar absorptivity and Sandell’s sensitivity were 1.01 × 104 L∙mol−1∙cm−1 and 0.0514 µg/mL, respectively. The elements of method validation stipulated by The International Conference on Harmonization [Q2 (R1)] were applied for hydralazine hydrochloride assay in pure and pharmaceutical tablet formulation. The average recoveries of the pure solution and the pharmaceutical formulation were 98.94% and 99.50%, respectively. The results were statistically compared by F-test, which indicates that the method can be precise and repeatable for both pure and pharmaceutical solutions. The method was found to be accurate, reproducible, and cost-effective, and validated for the assay of hydralazine in terms of the routine quality control.

Synthesis, Molecular Structure, Anti-Plasmodial, Antimicrobial and Anti-Oxidant Screening of (E)-1-(Phthalazin-1-yl)-1-[(Pyridin-2-yl)Ethylidene]Hydralazine and 1-[2-(1-(pyridine-3- yl)ethylidene)hydrazinyl]phthalazine

Two new hydralazine hydrochloride-derived Schiff bases: (E)-1-(Phthalazin- 1-yl)-1-[(Pyridin-2-yl)Ethylidene]Hydralazine (PPEH), and 1-[2-(1-(pyridine- 3-yl)ethylidene)hydrazinyl]phthalazine (PEHP), were synthesized and partially characterized by spectroscopic and crystallographic methods including IR and X-ray. The single-crystal X-ray diffraction (SCXRD) analysis of PEHP indicates that the hydralazine moiety of both ligands possesses the exocyclic C=N bond. Both, PPEH and PEHP were tested as antimicrobials and antiparasites. Just PEHP could be considered as slightly antiplasmodial and antibacterial agent. In effect, PPEH showed low antimicrobial activity against one bacterial strain with Minimum Inhibitory Concentration (MIC) value of 250 μg/ml while PEHP showed very interesting activity against 18 out of 19 bacterial strains with MIC of 31.25 - 250 μg/ml compared to the standard drug, amoxicillin. PPEH and PEHP showed higher reducing activity on ferric ions compared to Vitamin C. On the other hand, both hidrazaline synthetized derivatives showed as better reducing agents than Vitamin C on ferric ions, while again, only the PEHP showed slightly high inhibition of lipid peroxidation using Vitamin C as standard. Regarding their catalase activity, both compounds showed concentration dependent effect, but Vitamin C continued showing a higher stimulatory effect on the enzyme activity. Additionally, while PPEH showed less than 80% inhibition in the preliminary antiplasmodial assay and so was not considered for the dose-response studies, PEHP displayed an inhibition percentage of 83.60% and 50% Inhibitory Concentration (IC50) value of 44.13 μg/mL compared to the standard drug, artemisinin and was classified as slightly active.

Novel Hydralazine Schiff Base Derivatives and Their Antimicrobial, Antioxidant and Antiplasmodial Properties

Two novel Schiff bases, 3-[1-(2-(phthalazin-1-yl)hydrazono)ethyl)-1,3-oxa- zinane (PHEO) and 2-[(2-(phthalazin-1-yl)hydrazono)methyl]phenol (PHMP), derived from hydralazine hydrochloride, an effective drug against hypertension, were synthesized and characterized by spectroscopic methods, Infrared (IR), Proton Nuclear Magnetic Resonance (1H NMR) and Carbon-13 Nuclear Magnetic Resonance (13C NMR). PHEO showed low antimicrobial activity against one bacterial strain with MIC value of 250 μg/ml while PHMP showed interesting activity against 4 bacterial strains with MIC of 31.25 - 250 μg/ml compared to the standard drug, amoxicillin. PHEO and PHMP showed higher reducing activity on ferric ions compared to Vitamin C. On lipid peroxidation, PHEO showed higher inhibition while PHMP showed lower inhibition compared to Vitamin C. Both compounds presented lower stimulating effect and lower catalase activity compared to the standard Vitamin C. PHEO and PHMP showed less than 80% inhibition in the preliminary antiplasmodial assay and so were not considered for the dose-response studies.

Corrosion Inhibitory Studies of Novel Schiff Bases Derived from Hydralazine Hydrochloride on Mild Steel in Acidic Media

The inhibition performance of 1-hydralazinophthalazine (HPZ) (1), and synthesized1-(2-[(5-methylfuran-2-yl)methylene)] hydrazono) phthalazine (MFHPZ) (2), 1-(phthalazin-1(2H)-one) [(pyridin-2-yl) ethylidene] hydrazone (ACPHPZ) (3) and (2-acetylthiophene hydrazono) phthalazine (ACTHPZ) (4) has been investigated for mild steel in 1 M HCl. Compound 4 shows maximum inhibition efficiency of 93% at 5.0 × 10-3 M concentration. The evaluation of thermodynamics and activation parameters indicated spontaneous adsorption of the inhibitor molecules which takes place through chemisorption. The adsorption of 3 and 2 follows Langmuir adsorption isotherm and Temkin adsorption isotherm for 4 and 1. The inhibitor efficiency was of the order 4 > 3 > 1 > 2. Impedance study for the representative inhibitor compounds 4 and 3 showed that decrease in charge transfer resistance is responsible for effective protection of mild steel surface by the tested inhibitor.

Labetalol versus Hydralazine in the Management of Severe Pre-Eclampsia at Tertiary Hospitals in a Low-Resource Setting: A Randomised Controlled Trial

Objective: Intravenous labetalol and hydralazine are both considered first-line medications for the management of acute-onset, severe hypertension in pregnant and postpartum women. The study compared the efficacy and safety profile of intravenous labetalol and hydralazine in the control hypertension in severe pre-eclampsia. Materials and Methods: One hundred patients who presented with severe pre-eclampsia were randomized into two study groups. The fifty patients in each arm of the study received either intravenous labetalol or intravenous hydralazine for the control of blood pressure. Results: The mean age of the labetalol subjects was 28.6 ± 5.47 years while that of their hydralazine counterparts was 29.12 ± 5.77 years. The majority of respondents in both groups were primigravidae (76% vs. 78%) (P = 0.813). The number of doses of drug needed to significantly lower the mean systolic blood pressure was slightly lower in the labetalol group (2 doses) compared to the hydralazine group (5 doses) (t = 0.803Y, P = 0.977). The incidence of headaches which were the commonest complaints was comparable in both groups 8% and 10% of respondents respectively (P > 0.05). Conclusion: Although both intravenous labetalol and hydralazine are useful in patients with severe pre-eclampsia, the response to labetalol was better with comparable side effects.

Hydralazine Hydrochloride:An Alternative Complexometric Reagent for Total Iron Spotometric Determination

An alternative spectrophotometric method has been developed for total iron determination using flow injection analysis (FIA). The procedure is based on the coordination reaction between hydralazine and Fe2+ ions, which results in the formation of a purple complex monitored at 538 nm. For determination of total iron, Fe3+ ions were reduced using ascorbic acid. Under optimized conditions, a linear calibration graph (0.1 - 6.0 ?g?ml–1;n = 6) was obtained. The method allows LOD (3? of blank/slope = 0.06 ?g?ml–1) and LOQ (10? of blank/slope = 0.22 ?g?ml–1). The RSD ((s/ ) × 100) for a mixed standard containing 0.60 ?g?ml–1 Fe2+ and Fe3+ was 0.10% (n = 10). Recoveries of spiked samples were 94.3% - 106.0%. The analytical frequency was 60 h–1. The effect of possible interferences has been studied. The procedure was successfully applied for analysis of environmental samples. The real samples results were comparable with those obtained by the official method considering a paired t-test and 95% of confidence level.

Utilization of hydralazine as a reactive matrix for enhanced detection and on-MALDI-target derivatization of saccharides

Saccharides are a sort of ubiquitous and vital molecules within the whole life.However,the application of saccharides analysis with matrix-assisted laser desorption/ionization mass spectrometry(MALDI-MS)is restricted by their low ionization efficiency and the instability of the sialic acid fraction.Derivatization strategy based on nonreductive amination provides a good solution,however,this is often time consuming and may result in sample loss due to removal of excessive derivatization reagents.Herein,hydralazine(HZN)was utilized as a reactive matrix for labeling reducing saccharides directly on MALDI target which eliminated tedious sample preparation and avoided sample loss.After optimization,effective and reproducible on-MALDI-target derivatization of neutral and acidic saccharides was achieved in both positive and negative modes.Compared with 2,5-dihydroxybenzoic acid(DHB)and 9-aminoacridine(9-AA),HZN improved the detection sensitivity of reducing saccharides and provided more abundant fragment ions in MS/MS analysis.Moreover,26 kinds of neutral glycans and 5 kinds of sialic glycans were identified from ovalbumin(OVA)and bovine fetuin,respectively.Combined with the statistical models,this strategy could be used to distinguish and predict samples of 6 brands of beer,and discriminate 2 kinds of beer fermentation modes.In addition,HZN was applied for quantitative analysis of glucose in urine samples,and the obtained urine glucose concentrations of diabetic patients were consistent with the clinical test results,showing the potential of qualitative and quantitative analysis of reducing saccharides in complex samples.

Acrolein as a novel therapeutic target for motor and sensory deficits in spinal cord injury

In the hours to weeks following traumatic spinal cord injuries （SCI）, biochemical processes are initiated that further damage the tissue within and surrounding the initial injury site： a process termed secondary injury. Acrolein, a highly reactive unsaturated aldehyde, has been shown to play a major role in the secondary injury by contributing significantly to both motor and sensory defi- cits. In particular, efforts have been made to eluddate the mechanisms of acrolein-mediated dam- age at the cellular level and the resulting paralysis and neuropathic pain. In this review, we will highlight the recent developments in the understanding of the mechanisms of acrolein in motor and sensory dysfunction in animal models of SCI. We will also discuss the therapeutic benefits of using acrolein scavengers to attenuate acrolein-mediated neuronal damage following SCI.

Synthesis, Molecular Structure and Anti-Onchocercal Studies of 1-(Phthalazin-1(2H)-one)[(Pyridin-2-yl)ethylidene]hydrazone

The novel ligand, 1-(phthalazin-1(2H)-one)[(pyridin-2-yl)ethylidene]hydrazone,(APN), derived from the antihypertensive drug, hydralazine hydrochloride, was synthesized and characterized by spectroscopic methods (IR, 1H NMR). The X-ray crystallographic data indicates that APN has an exocyclic C=N bond on the hydralazine moiety. APN revealed significant anti-onchocercal activity with IC50 values of 0.3125 μg/mL on microfilaria and 10 μg/mL on adult worms compared to the standard drug, ivermectin.

基于共振光散射光谱法测定药品中盐酸肼屈嗪含量

为了研究药品中盐酸肼屈嗪含量检测的新方法,本文采用共振光散射光谱法以Clark-Lubs缓冲液为介质分析盐酸肼屈嗪与十二烷基苯磺酸钠反应的光散射强度参数关系。研究发现:在pH 1.4的Clark-Lubs缓冲介质中适量盐酸肼屈嗪与十二烷基苯磺酸钠水溶液发生π-π电荷转移和离子缔合反应,所得产物的共振光散射最大发射波长在402 nm处,盐酸肼屈嗪浓度在0.125～1.00 mg·L^(-1)范围内呈线性关系,相关系数R为0.9998,检出限为0.035 mg·L^(-1),回收率在99.08%～100.8%之间。所拟方法适用于分析常温下盐酸肼屈嗪与光散射强度的参数关系,可应用于药品中盐酸肼屈嗪含量的测定。