Inhibition Action Research Articles

Surface equilibrium and thermodynamics implications of the corrosion inhibition of mild steel in acid medium using quinine inhibitor

One problem faced by industries is the degradation of their metal pipes and machine parts which are exposed to chemically aggressive media. This has necessitated the search for cheap and non-toxic substances that can limit corrosion. The inhibition potential of quinine against the corroding of mild steel in 1M HCl medium was tested under varied concentration of quinine and temperature, using gravimetric method. The results showed that corrosion rate and weight loss decreased with increasing concentration of quinine and temperature up to 40 °C, while surface coverage, θ, and inhibition efficiency IE, increased as the concentration and temperature increased. Surface equilibrium studies showed that the inhibition action followed the Freundlich isotherm with value of adsorption intensity that suggests a cooperative adsorption mechanism in heterogeneous sites while thermodynamic analysis implied that the process of inhibition was endothermic having a positive value of ΔH (17.384 kJ mol-1), enthalpy-driven with a negative ΔS (-64.434 kJ mol-1K-1) and occurred by a physisorption mechanism. Positive ΔG obtained at the studied temperatures suggests that the corrosion process was rendered passive and unfeasible. These findings project quinine as a promising inhibitor for chemical degradation of mild steel in hydrochloric acid medium.

Green Inhibition of Corrosion of Aluminium Alloy 5083 by Artemisia annua L. Extract in Artificial Seawater

Plant extracts are increasingly being examined in the corrosion inhibition of metal and alloys in various environments due to their potent antioxidant properties. The use of Artemisia annua L. aqueous extract (AAE) as an aluminium alloy 5083 (ALA) corrosion inhibitor in artificial seawater (ASW) was investigated using electrochemical tests and spectroscopy tools, while the active biocompounds found in AAE were analyzed using high-performance liquid chromatography (HPLC). Electrochemical results showed that AAE acts as an anodic inhibitor through the physisorption (ΔG ≈ -16.33 kJ mol-1) of extract molecules on the ALA surface, thus reducing the active sites for the dissolution of the alloy in ASW. Fourier-transform infrared spectra confirmed that phenolic acids found in AAE formed the surface layer that protects ALA against the corrosive marine environment, while HPLC analysis confirmed that the main phytoconstituents of AAE were chlorogenic acid and caffeic acid. The inhibition action of phenolic acids and their derivatives found in the AAE was based on the physisorption of caffeic acid on the ALA surface, which improved physicochemical properties of the barrier film and/or conversion of Al3+ to elemental aluminium by phenolic acids as reducens, which slowed down the diffusion rate of Al3+ to or from the ALA surfaces. The protective effect of the surface layer formed in the presence of AAE against ASW was also confirmed by inductively coupled plasma-optical emission spectrometry (ICP-OES) whereby the measured concentration of Al ions after 1 h of immersion of ALA in the pure ASW was 15.30 μg L-1 cm-2, while after the addition of 1 g L-1 AAE, the concentration was 3.09 μg L-1 cm-2.

The inhibitive action of 2-mercaptobenzothiazole on the porosity of corrosion film formed on aluminum and aluminum–titanium alloys in hydrochloric acid solution

2-Mercaptobenzothiazole (2-MBT) in a solution of 0.5 M HCl is an effective corrosion inhibitor for aluminum and aluminum–titanium alloys. Tafel polarization and electrochemical impedance spectroscopy (EIS) were employed to assess this heterocyclic compound’s anticorrosive potential and complementary by scanning electron microscope (SEM) and calculating porosity percentage in the absence and presence of various inhibitor concentrations. Inhibition efficiency (IE%) was strongly related to concentration (10–6–10–3 M). Temperature’s effect on corrosion behavior was investigated. The data exhibited that the IE% decreases as the temperature increases. An increase in activation energy (Ea) with increasing the inhibitor concentration and the decrease in the IE% value of the mentioned compound with raising the temperature indicates that the inhibitor molecules are adsorbed physically on the surface. Thermodynamic activation parameters for Al and Al–Ti alloy dissolution in both 0.5 M HCl and the inhibited solution were calculated and discussed. According to Langmuir’s adsorption isotherm, the inhibitor molecules were adsorbed. The evaluated standard values of the enthalpy (Delta {H}_{ads.}^{o}), entropy (Delta {S}_{ads.}^{o}) and free energy changes (Delta {G}_{ads.}^{o}) showed that Delta {H}_{ads.}^{o} and Delta {G}_{ads.}^{o} are negative, while Delta {S}_{ads.}^{o} was positive. The formation of a protective layer adsorbed on the surfaces of the substrates was confirmed with the surface analysis (SEM). The porosity percentage is significantly reduced in the inhibitor presence and gradually decreased with increasing concentration. Furthermore, the density functional theory (DFT) and Monte Carlo (MC) simulations were employed to explain the variance in protecting the Al surface from corrosion. Interestingly, the theoretical findings align with their experimental counterparts. The planarity of 2-MBT and the presence of heteroatoms are the playmakers in the adsorption process.

Action of 2,6-Dichloro-1,4-benzoquinone on the O2-Evolving Activity of Photosystem II in Chlamydomonas reinhardtii Cells with and without Cell Wall: Inhibitory Effect of Its Oxidized Form

Chlamydomonas reinhardtii is a widely used object in studies on green algae concerning both photosynthesis aspects and possible biotechnological approaches. The measurement of the maximum O2 evolution by photosystem II (PSII) in living algal cells in the presence of artificial acceptors is one of the commonly used methods for determining the photosynthetic apparatus state or its change as compared to a control, parent strain, etc., because PSII is the most sensitive component of the thylakoid membrane. The present study shows the need to use low concentrations of 2,6-dichloro-1,4-benzoquinone (DCBQ) paired with potassium ferricyanide (FeCy) for achieving the maximum O2 evolution rate, while a DCBQ concentration above certain threshold results in strong suppression of O2 evolution. The required DCBQ concentration depends on the presence of the cell wall and should be exactly ~0.1 mM or in the range of 0.2-0.4 mM for cells with and without a cell wall, respectively. The inhibition effect is caused, probably, by a higher content of DCBQ in the oxidized form inside cells; this depends on the presence of the cell wall, which influences the efficiency of DCBQ diffusion into and out of the cell, where it is maintained by FeCy in the oxidized state. The possible mechanism of DCBQ inhibition action is discussed.

Basal ganglia network dynamics and function: Role of direct, indirect and hyper-direct pathways in action selection

ABSTRACT Basal ganglia (BG) are a widely recognized neural basis for action selection, but its decision-making mechanism is still a difficult problem for researchers. Therefore, we constructed a spiking neural network inspired by the BG anatomical data. Simulation experiments were based on the principle of dis-inhibition and our functional hypothesis within the BG: the direct pathway, the indirect pathway, and the hyper-direct pathway of the BG jointly implement the initiation execution and termination of motor programs. Firstly, we studied the dynamic process of action selection with the network, which contained intra-group competition and inter-group competition. Secondly, we focused on the effects of the stimulus intensity and the proportion of excitation and inhibition on the GPi/SNr. The results suggested that inhibition and excitation shape action selection. They also explained why the firing rate of GPi/SNr did not continue to increase in the action-selection experiment. Finally, we discussed the experimental results with the functional hypothesis. Uniquely, this paper summarized the decision-making neural mechanism of action selection based on the direct pathway, the indirect pathway, and the hyper-direct pathway within BG.

Exploration of the inhibition action of TPGS on tumor cells and its combined use with chemotherapy drugs

D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) is a commonly used nonionic surfactant used as a pharmaceutical carrier in different drug delivery systems. TPGS can reverse P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) and also has anticancer activities. It suggests that when designing antitumor drug preparation, it’s necessary to take into account the antitumor activity of TPGS. Our in vivo studies showed that TPGS exerted the strongest cytotoxicity in MCF-7-ADR cells when compared with seven other tumor cell lines. The further study revealed TPGS caused apoptosis and blocked MCF-7 cell growth in G2/M phase. Mechanistic insights suggested that TPGS increased intracellular calcium ion concentrations, leading to apoptosis via the mitochondrial pathway. Furthermore, two in vivo experiments were performed. One was TPGS, and DOX solution was administered by tail vein injection on MCF-7-ADR tumor bearing nude mice. The other was temperature sensitive TPGS gel (TPGS-TG) was administered by intratumoral injection on MCF-7-ADR tumor bearing nude mice combined with paclitaxel albumin nanoparticles (Abraxane®) administered by tail vein injection. The findings confirmed that TPGS could play its role in anti-tumor to reduce the toxicity of chemotherapeutic drugs and improve the efficiency of drug-resistant tumors, thereby enhancing the development of safe oncology therapeutics.

Evaluation of corrosion mitigation properties of pyridinium-based ionic liquids on carbon steel in 15% HCl under the hydrodynamic condition: Experimental, surface, and computational approaches

The corrosion process severely damages the carbon steel during the acidization. The present investigation described the corrosion inhibition application of two ionic liquids: 1-Butylpyridinium chloride (BPC) and 1-Butylpyridinium hexafluorophospate (BPH), for the protection of carbon steel in 15 % HCl under the hydrodynamic condition at 1500 rpm. The estimated results obtained by weight loss support the inhibitive performance of BPs are 90.0 % (BPC) and 72.5 % (BPH). The EIS results point out the rising values of Rct with the increasing amount of BPs and approach the highest value of 262.4 Ω cm2 (BPC) and 125.4 Ω cm2 (BPH). The PDP reveals the anodic nature of BPs inhibitive action. The Dubinine Radushkevich (d-RIM) adsorption isotherm model provides accurate fitting estimated data. The negative values of ΔHoads represent the exothermic nature of adsorption. The contact angle value is less (26.4°) for BPs free steel sample. However, a significant increase occurs in the contact angle values upon adding BPC (84.9°) and BPH (67.8°). The SEM, optical profilometry, contact angle, and XPS confirmed the presence of an adsorptive layer of BPs. DFT further suggests the better inhibitive performance of BPC than BPH.

Date Palm Seed Extract for Mild Steel Corrosion Prevention in HCl Medium

The inhibition effects of the date palm seed extract corrosion of mild steel in 0.5 M HCl at different concentrations are investigated by potentiodynamic polarisation (PDP), electrochemical impedance spectroscopy (EIS) and weight loss tests. Additionally, this study provides a fundamental understanding of aromatic adsorption on iron (Fe) surfaces. Furthermore, the surface morphology and the extracts are performed using scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). The maximum inhibition efficiency of 95, 96, and 91% were realised at 1400 mg/L for PDP, EIS, and weight loss, respectively. The inhibitive action of the DPS extract against mild steel corrosion in an acid solution has been supported by SEM analysis. The FTIR showed that the extract contained hydroxyl (−OH) and methoxyl (−OCH3) functional groups. The DFT depicted the adsorption sites at the oxygen (O) and carbon (C) atoms as deduced from the Fukui functions, Mulliken atomic charge, and the highest occupied molecular orbital-lowest occupied molecular orbital (HOMO-LUMO) analysis. The DPS preferred to form chemical bonds by donating electrons to the Fe surface. The coordinate bonds between the O and C atoms and the metal surface resulted in a high inhibition efficiency value. In conclusion, date palm seed extract is an effective inhibitor to protect mild steel from corrosion in an acidic medium.

Corrosion and bacterial growth mitigation in the desalination plant by imidazolium based ionic liquid: Experimental, surface and molecular docking analysis

The desalination plants wieldy used CuNi alloys. However, it faces a fundamental corrosion problem in a 3.5% NaCl solution containing sulfide ions. In this research, we have examined ionic liquid's corrosion and bacterial inhibition activity, i.e., 1-Dodecyl-3-methylimidazolium iodide (IMD-IL). The obtained data from weight loss and electrochemical reveals the corrosion inhibitive performance of IMD-IL is 96.8% at 100 mg/L. The EIS suggests increasing the charge transfer resistance and film resistance with increasing IMD-IL amount, supporting the inhibitive action of IMD-IL molecules. The biological activity results reveal the deactivation of SRB action after the addition of IMD-IL molecules. The SEM and EDX studies support the IMD-IL adsorption onto the CuNi surface. The molecular docking results confirmed that IMD-IL could bind the cytochrome c, inhibiting its activity and thereby interrupting the electron transport pathway between bacteria and the CuNi.

Matrine restrains the development of colorectal cancer through regulating the AGRN/Wnt/β-catenin pathway.

Colorectal cancer is a common malignant digestive tract tumor. This study aimed to explore the biological role and potential underlying mechanism of matrine in colorectal cancer. The mRNA expression of AGRN was measured using RT-qPCR. Cell proliferation, migration, invasion and apoptosis were determined using CCK-8, EdU, transwell assays and flow cytometry, respectively. Xenograft tumor experiment was performed to explore the action of matrine and AGRN on tumor growth in colorectal cancer in vivo. Immunohistochemistry (IHC) assay was applied for AGRN, β-catenin, and c-Myc expression in the tumor tissues from mice. Matrine dramatically repressed cell growth and reduced the level of AGRN in colorectal cancer cells. AGRN expression was boosted colorectal cancer tissues and cells. AGRN downregulation depressed cell proliferation, migration, invasion, and enhanced cell apoptosis in colorectal cancer cells. Moreover, matrine showed the anti-tumor effects on colorectal cancer cells via regulating AGRN expression. AGRN knockdown could inactivate the Wnt/β-catenin pathway in colorectal cancer cells. We found that AGRN downregulation exhibited the inhibition action in the progression of colorectal cancer by modulating the Wnt/β-catenin pathway. In addition, matrine could inhibit the activation of the Wnt/β-catenin pathway through regulating AGRN in colorectal cancer cells. Furthermore, xenograft tumor experiment revealed that matrine treatment or AGRN knockdown repressed the development of colorectal cancer via the Wnt/β-catenin pathway in vivo. Matrine retarded colorectal cancer development by modulating AGRN to inactivate the Wnt/β-catenin pathway.

Alpha amylase inhibitor as an Anti-diabetic potential from medicinal plants: A Review

Alpha amylases cleave the starch like molecules and led to increase in blood sugar level in diabetic patients then in order to manage it the inhibition action is carried out by their inhibitors. The α-amylase inhibitors catalyses the process of endo-hydrolysis of α (1→ 4) glycosidic linkage present in starch which ultimately led to decrease in the starch hydrolysis process. It also affects the carbohydrate absorption in the intestine. In 1945, the first alpha amylase inhibitor was reported from beans. It has already been isolated from various plant species namely, Hibiscus sabdariffa.L, Geranium pratense L and Cedrus libani A. Rich with inhibition percentage of 100, 43 and 31 respectively. The studies have already been reported on inhibitors and their interactions with human pancreatic alpha amylases are made .In-vitro and in vivo tests has already been done by various researchers which showed a significant drop in blood sugar level of a normoglycemic mice after an extract from the leaves of Bersama abbyssinica was tested for its potential effect as anti-diabetic.

Mikania micrantha extract/KI blend as a novel synergistic inhibitor for steel corrosion in concentrated H3PO4 solution

Mikania micrantha extract (MME) was prepared by reflux extraction from the exotic invasive weed of Mikania micrantha using ethanol water solution as the solvent. The synergistic inhibition effect and mechanism of MME and potassium iodide (KI) on the corrosion of cold rolled steel (CRS) in 4.0 M H3PO4 solution was investigated by gravimetric, electrochemical and surface analysis techniques for the first time. The results show that either MME or KI has moderate inhibitive action, and the maximum inhibition efficiency is below 65 % at 20 ℃. However, incorporation MME with KI can produce a synergism (s > 1), and obtain a pleasant inhibition of 92.9%. The adsorption of MME on CRS surface obeys Freundlich isotherm, while KI and MME/KI complex follow Langmuir isotherm. They are all mixed-type inhibitors, and MME/KI mixture significantly retards the electrochemical corrosion comparing with individual MME or KI. The process of electrochemical corrosion is controlled by charge transfer, and the charge transfer resistance follows the order of MME/KI > KI > MME. SEM and AFM demonstrate that the corrosion of CRS surface is efficiently retarded by the blend of MME and KI. From FTIR and XPS analysis, the formed layer of the synergistic inhibited CRS surface is mainly composed of the organic compounds with polar groups in MME. There is also a synergistic inhibition of the major components (rutin, quercetin, chlorogenic acid and ferulic acid) with KI. MME/KI can be deemed as a novel efficient inhibitor for steel in concentrated phosphoric acid, which develops an original path for the utilization of Mikania micrantha in the field of metallic corrosion and protection.

Inhibition Action of Cationic Gemini Surfactants on Mild Steel Corrosion in 1 N HCl

Inhibition Action of Cationic Gemini Surfactants on Mild Steel Corrosion in 1 N HCl

Chemical and Electrochemical Studies on Expired Lioresal Drugs as Corrosion Inhibitors for Carbon Steel in Sulfuric Acid

Lioresal is a muscle relaxer and an antispasmodic agent, known as Lioresal. The active ingredient is β-(Aminomethyl)-p-chlorohydrocinnamic acid, a racemic mixture of the R,(-) and S, (+) isomers. It affects directly the spinal cord with adverse effects including drowsiness, dizziness, weakness, fatigue, headache, trouble sleeping, nausea and vomiting, urinary retention, or constipation. Therefore, the accumulation of expired or unused Lioresal in our home is so dangerous and harmful for our children. The present work introduces an idea for using expired Lioresal as a corrosion inhibitor for steel in 1.0 M H2SO4. The effect of both concentration and temperature were studied. The inhibition efficiency was found to increase with concentration and decreased with rising temperature. Chemical, electrochemical, and analytical techniques, namely, gravimetric, thermometric, gasometric, acidimetric, AAS, and potentiodynamic polarization were used to evaluate the inhibition action of the expired Lioresal drugs. The inhibition performance is due to the adsorption and adhesion of drugs constituent molecules on the steel surface. The adsorption was found to obey Langmuir isotherm. The surface area available for the anodic dissolution of iron and cathodic hydrogen evolution process diminishes without changing the reaction mechanism. The values of Ecorr. readings slowly decrease to negative values, showing that these inhibitors are mixed-type inhibitors mainly cathodic inhibitors. The data obtained from different techniques are in good agreement with each other. Electrochemical and analytical Techniques are efficient and accurate in the determination of the corrosion rate and inhibition performance of expired drugs in an aqueous medium.

Bactericide Activity of Cellulose Acetate/Silver Nanoparticles Asymmetric Membranes: Surfaces and Porous Structures Role.

The antibacterial properties of cellulose acetate/silver nanoparticles (AgNP) ultrafiltration membranes were correlated with their integral asymmetric porous structures, emphasizing the distinct features of each side of the membranes, that is, the active and porous layers surfaces. Composite membranes were prepared from casting solutions incorporating polyvinylpyrrolidone-covered AgNP using the phase inversion technique. The variation of the ratio acetone/formamide and the AgNP content resulted in a wide range of asymmetric porous structures with different hydraulic permeabilities. Comprehensive studies assessing the antibacterial activity against Escherichia coli (cell death and growth inhibition of bacteria in water) were performed on both membrane surfaces and in E. coli suspensions. The results were correlated with the surface chemical composition assessed by XPS. The silver-free membranes presented a generalized growth of E. coli, which is in contrast with the inhibition patterns displayed by the membranes containing AgNP. For the surface bactericide test, the growth inhibition depends on the accessibility of E. coli to the silver present in the membrane; as the XPS results show, the more permeable membranes (CA30 and CA34 series) have higher silver signal detected by XPS, which is correlated with a higher growth inhibition. On the other hand, the inhibition action is independent of the membrane porous structure when the membrane is deeply immersed in an E. coli inoculated suspension, presenting almost complete growth inhibition.

Inhibition Ras/MEK/ERK pathway: An important mechanism of Baihu Jia Guizhi Decoction ameliorated rheumatoid arthritis

Ethnopharmacological relevanceAlleviating rheumatism by inhibiting synovitis is a routine treatment for rheumatoid arthritis (RA). Baihu Jia Guizhi Decoction (BHJGZ) is a classic prescription and has a long history of application for treating RA with a good anti-inflammatory action. However, the underlying molecular mechanisms have not been fully elucidated. Aim of the studyThis work aimed to decipher the potential mechanism of BHJGZ against RA focusing on Ras/MEK/ERK pathway. Materials and methodsBased on the prediction of network pharmacology, the inhibition action of BHJGZ on Ras/MEK/ERK pathway was firstly validated in vivo and in vitro. Moreover, the affinity with the ingredients of BHJGZ in serum and the targets of Ras/MEK/ERK pathway were evaluated. Finally, the efficacy of BHJGZ for relieving RA was assessed in AA rats. ResultsThe Ras/MEK/ERK pathway was predicted by network pharmacology as one of important mechanisms of BHJGZ to treat RA. The high expression of Ras protein in synovitis of AA rats was significantly reduced by the treatment with BHJGZ, and the activation of Ras/MEK/ERK pathway in vivo and in vitro was also markedly inhibited (p < 0.05 or p < 0.01). Moreover, the level of p-ERK/ERK, IL-6 and TNF-α in vitro were further suppressed after Ras or MEK was inhibited by mirdametinib or lonafarnib respectively (p < 0.01). Furthermore, the results of molecular docking showed a good affinity and stable binding with the ingredients of BHJGZ in serum and multiple key proteins of the Ras/MEK/ERK pathway. Finally, paw swelling, paw circumference and pathological changes of joint synovitis were significantly reduced by BHJGZ in AA rats (p < 0.05). ConclusionThe inhibition of Ras/MEK/ERK pathway is one of crucial mechanisms of BHJGZ for ameliorating synovitis of RA.

Inhibition of hydrogen evolution and corrosion protection of negative electrode of lead-acid battery by natural polysaccharide composite: Experimental and surface analysis

The investigated research illustrates the synthesis of composite polymer (GG-VA) using natural polysaccharide (Guar Gum/GG) and vinyl acetate (VA) and screening their inhibitive performance for the hydrogen gas evolution and corrosion inhibition of lead-acid battery negative electrode, i.e., Pb in 5.0 M H2SO4. The developed inhibitor is an environmentally friendly biological molecule and has been used for lead acid batteries for the first time as an additive. The methodology used to evaluate GG-VA inhibitive performance included hydrogen evolution and electrochemical methods, i.e., EIS and PDP. The corrosion inhibition performance of GG-VA is 88.57 %. The Pb surface was screened for GG-VA adsorption via SEM and AFM. The experimental data confirmed the reduction in hydrogen gas evolution with the addition of GG-VA. The EIS result supports the increasing Rct values with the rising GG-VA amount corresponding to the GG-VA adsorption. PDP data reveals the mixed inhibition action and reduction in icorr values with the addition of GG-VA. The increasing temperature causes a decrease in GG-VA performance. GG-V adsorption over the Pb surface was best described by Langmuir isotherm. The Ea data reveals the increase in the energy barrier for corrosion reaction and H2 gas evolution in the presence of GG-VA. The SEM and AFM support the adsorbed layer of GG-VA formation at the Pb surface.

Adsorption and corrosion inhibition performance of rice bran extract on carbon steel in aqueous chloride solution: Experimental, computational and theoretical studies

In this study, an ecofriendly corrosion inhibitor made of waste rice bran was produced to reduce corrosion caused by chloride on reinforcement. Electrochemical results revealed that with increasing inhibitor concentration the inhibition efficiency of the rice bran extract (RBE) reached the maximum value of 98% at an optimum concentration of 4.5%. The existence of carbonaceous passive film over the steel surface was established by X-ray photoelectron spectroscopy (XPS). Quantum mechanics and Molecular simulations evidenced the adsorption of phytochemicals onto the steel surface thus, affirming the inhibition action of the rice bran extract.

The anticorrosive applications of anionic surfactant on AA2024-T3 aluminum alloy in alkaline medium: Experimental and theory

Inhibitory effects of sodium abietate (SA) and sodium lignin sulfonate (SLS) were discussed using a series of tests and theoretical calculations. Experimental outcomes obtained via weight loss and electrochemistry data showed that SA and SLS significantly inhibited the corrosion of AA2024-T3 Aluminum alloys in NaOH media. The inhibition efficiency (η%) for SA and SLS was up to 96.02% and 98.82% at 5 × 10−3 mol·L−1, respectively. SA and SLS acted as anode-dominated mixed-type inhibitors in aggressive solutions as recorded by electrochemical methods. In addition, the surface analyses further corroborated the protection of the metal surface from corrosion as added with SA and SLS that can form an adsorbed film on the metal surface. The adsorption obeyed Langmuir isotherm which illustrated the adsorptions of the SA and SLS were a mix of physical and chemical adsorptions. Moreover, the inhibition performance of both inhibitors with the molecular structure shown in quantum chemical calculations and molecular dynamics simulation found that be suitable for explaining the inhibitive action of the two. The study suggests SA and SLS as green sources appropriate for anticorrosive applications.

Preclinical exploration of combined glucagon inhibition and liver-preferential insulin for treatment of diabetes using in vitro assays and rat and mouse models

Aims/hypothesisNormalisation of blood glucose in individuals with diabetes is recommended to reduce development of diabetic complications. However, risk of severe hypoglycaemia with intensive insulin therapy is a major obstacle that prevents many individuals with diabetes from obtaining the recommended reduction in HbA1c. Inhibition of glucagon receptor signalling and liver-preferential insulin action have been shown individually to have beneficial effects in preclinical models and individuals with diabetes (i.e. improved glycaemic control), but also have effects that are potential safety risks (i.e. alpha cell hyperplasia in response to glucagon receptor antagonists and increased levels of liver triacylglycerols and plasma alanine aminotransferase activity in response to glucagon receptor antagonists and liver-preferential insulin). We hypothesised that a combination of glucagon inhibition and liver-preferential insulin action in a dual-acting molecule would widen the therapeutic window. By correcting two pathogenic mechanisms (dysregulated glucagon signalling and non-physiological distribution of conventional insulin administered s.c.), we hypothesised that lower doses of each component would be required to obtain sufficient reduction of hyperglycaemia, and that the undesirable effects that have previously been observed for monotreatment with glucagon antagonists and liver-preferential insulin could be avoided.MethodsA dual-acting glucagon receptor inhibitor and liver-preferential insulin molecule was designed and tested in rodent models (normal rats, rats with streptozotocin-induced hyperglycaemia, db/db mice and mice with diet-induced obesity and streptozotocin-induced hyperglycaemia), allowing detailed characterisation of the pharmacokinetic and pharmacodynamic properties of the dual-acting molecule and relevant control compounds, as well as exploration of how the dual-acting molecule influenced glucagon-induced recovery and spontaneous recovery from acute hypoglycaemia.ResultsThis molecule normalised blood glucose in diabetic models, and was markedly less prone to induce hypoglycaemia than conventional insulin treatment (approximately 4.6-fold less potent under hypoglycaemic conditions than under normoglycaemic conditions). However, compared to treatment with conventional long-acting insulin, this dual-acting molecule also increased triacylglycerol levels in the liver (approximately 60%), plasma alanine aminotransferase levels (approximately twofold) and alpha cell mass (approximately twofold).Conclusions/interpretationWhile the dual-acting glucagon receptor inhibitor and liver-preferential insulin molecule showed markedly improved regulation of blood glucose, effects that are potential safety concerns persisted in the pharmacologically relevant dose range.Graphical abstract