Protein-Based Bioscavengers of Organophosphorus Nerve Agents
Brian J. Lukey, James A. Romano, Salem Harry in Chemical Warfare Agents, 2019
The notion of a protein bioscavenger is not a novel concept. In the late 1950s, A.R. Main demonstrated that an exogenous injection of an arylesterase provides protection against multiple LD50s of parathion in rats (Main, 1956). Because the bioscavenger can inactivate nerve agents before these toxic compounds inhibit AChE, early scavenger administration could avoid the onset of a toxic insult from nerve agent poisoning. While research has demonstrated the utility of this approach in vivo, stoichiometric bioscavengers have one main disadvantage in that once phosphylated by a molecule of nerve agent, the enzyme is unable to bind to another nerve agent molecule. As a result, the level of protection is directly proportional to the concentration of unbound, active bioscavenger in circulation. Therefore, a high concentration of stoichiometric bioscavenger is required to protect against multiple LD50s of a nerve agent exposure (Ashani and Pistinner, 2004; Lenz et al., 2007).
Hazard Characterization and Dose–Response Assessment
Ted W. Simon in Environmental Risk Assessment, 2019
The difference between toxicodynamics and toxicokinetics is evident in a very recent risk assessment of the organophosphate (OP) pesticide chlorpyrifos. The MOA for OPs is well known—inhibition of cholinesterases, with toxicity manifested as central and peripheral cholinergic effects.200 Thionophosphorus OPs such as chlorpyrifos do not directly inhibit acetyl cholinesterase (AChE), but must first be metabolized to the oxygen analog, or oxon, by CYP450 mixed-function oxidases, mainly occurring in the liver. Paraoxonase 1 (PON1) is an arylesterase that metabolizes organophosphate compounds. Chlorpyrifos oxon is inactivated by the enzyme paraoxonase (PON1) in the liver and other tissues,201,202 Genetic polymorphisms exist in the PON1 gene, and lifestyle factors such as the use of cholesterol-lowering medications and alcohol consumption may increase PON1 activity.203–206
High Carbohydrate Diet-Induced Metabolic Syndrome in the Overweight Body
Nilanjana Maulik in Personalized Nutrition as Medical Therapy for High-Risk Diseases, 2020
Turan’s group and others emphasized that MetS is also characterized with increased oxidative stress, a condition due to an imbalance between production and scavenging of oxidants in the antioxidant system (Vendemiale, Guerrieri et al. 1995; Bonomini, Rodella et al. 2015; Okatan, Tuncay et al. 2015; Bhatti, Bhadada et al. 2016; Gregorio, De Souza et al. 2016). Increased oxidative stress can play an important role in the pathogenesis of various diseases including MetS (Roberts and Sindhu 2009; Bonomini, Rodella et al. 2015), in part due to its amplification by a concomitant antioxidant deficiency which may favor the propagation of oxidative alterations from intra- to extracellular spaces. Similar to other studies (Galassetti 2012; Korkmaz, Altinoglu et al. 2013; Okatan, Tuncay et al. 2015), our findings, related with significantly increased total oxidative status and decreased total antioxidant status in sera of rats with MetS, support these statements. These changes may further affect the impairment of insulin signaling, which further leads to insulin resistance. Indeed, previous studies using a high sucrose diet have shown a marked glucose intolerance in MetS modeled experimental animals (Pagliassotti, Prach et al. 1996; Brenner, Rimoldi et al. 2003). Additionally, they have shown significantly decreased serum paraoxonase and arylesterase activities in MetS group. Since the antioxidant properties of HDLs are attributable to serum paraoxonase and arylesterase activities (James 2006), these activities seem to be crucial in the relation to increased oxidative stress and organ dysfunction, particularly in terms of cardiovascular pathologies in rats with MetS (Kagota, Maruyama et al. 2013; Eren, Abuhandan et al. 2014).
Serum paraoxonase activity in patients with ischaemic and nonischaemic dilated cardiomyopathy
Published in Acta Cardiologica, 2018
Fatih Gungoren, Tunay Senturk, Alper Ozturk, Kerem Koz, Emre Sarandol, Dilek Yesilbursa, Sumeyye Gullulu, Guven Ozkaya, Ali Aydinlar
B-type natriuretic peptide (BNP) is a well-known biomarker, commonly used for the diagnosis and prognosis of patients with heart failure [5]. Paraoxonase-1 (PON1) is a high-density lipoprotein (HDL)-associated enzyme, and has antioxidant features. PON1 is an esterase and lactonase and hydrolyses lipoprotein-associated peroxides and lactones [6–8]. Tang et al. [9] suggested that there are decreased levels of serum arylesterase activity in patients with systolic HF and also suggested that decreased serum arylesterase activity was related to a higher risk of major adverse cardiac events. Another study demonstrated that the activity of paraoxonase-1 was significantly reduced in patients with HF versus controls [10]. Karabacak et al. [11] reported that there are increased levels of total oxidative status in patients with nonischaemic HF.
Prophylactic effect of probiotics fortified with Aloe vera pulp nanoemulsion against ethanol-induced gastric ulcer
Published in Toxicology Mechanisms and Methods, 2021
Jihan Hussein, Mona A. El-Bana, Mehrez E. El-Naggar, Yasmin Abdel-Latif, Samah M. El-Sayed, Dalia Medhat
Serum paraoxynase (POX) activity was estimated by spectrophotometer. The arylesterase activity of paraoxonase in samples was evaluated using a spectrophotometer using phenylacetate as a substrate. In this test, arylesterase/paraoxonase catalyzes phenyl acetate cleavage, leading to the production of phenol. Levels of phenol were determined by measuring the change in the absorbance at 270 nm at 25 °C. the working reagent was 20 mM Tris/HCl buffer, pH 8.0, containing 1 mM CaCl2 and 4 mM phenylacetate. After a 20-s lag period, samples diluted 1:3 in buffer were introduced, and the change in absorbance was measured. A UV I8 Recording Spectrophotometer was used to measure absorbance at 270 nm every 15 s for 120 s (Higashino et al. 1972; Hussein et al. 2013).
Chemoprotection by Kolaviron of Garcinia kola in Benzene-induced leukemogenesis in Wistar rats
Published in Egyptian Journal of Basic and Applied Sciences, 2022
Olaniyi Solomon Ola, Esther Oladayo Ogunkanmbi, Emmanuel Babatife Opeodu
Plasma AOPP was determined by the method described by Witko et al. [26] as modified by Zhang et al. [27]. Briefly, plasma (100 μl) was added to 400 μl of phosphate buffer saline (PBS) solution and 25 μl of 1.16 M potassium iodide was then added followed 2 min later by 50 μl of acetic acid. The absorbance of the reaction mixture was immediately read at 340 nm against a blank containing 500 μl of PBS, 25 μl of 1.16 M potassium iodide and 50 μl of acetic acid. Plasma total thiol was measured spectrophotometrically using DTNB (2,2’-dinitro-5,5’-dithiodibenzoic acid) [28]. Arylesterase activity was determined using phenylacetate as the substrate following the procedure described by Erdem et al. [29].
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