aldehyde oxidase
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2021 ◽  
pp. 4639-4648
Author(s):  
Joseph C Mordi ◽  
Fidelis Ifeakachuku Achuba ◽  
Patrick Chukwuyenum Ichipi-Ifukor ◽  
Gift Emete ◽  
Azukaego Thomas Hughs Mokogwu ◽  
...  

The use of medicinal plants in the treatment of harmful impacts of xenobiotics in animals is attracting an increasing attention in recent times. The aim of the current study is to assess the preventive potential of Costus afer aqueous leaves extract (CAAE) in treating metabolic aberrations imposed by crude oil contaminated diet inWistar albino rats. Six groups of rats were treated as follows: A = Normal diet; B=Normal diet + 100 mg/kg body weight of CAAE; C =Normal diet + 200 mg/kg body weight of CAAE; D= Crude oil contaminated diet; E= crude oil contaminated diet + 100 mg/kg body weight of CAAE, F = crude oil contaminated diet + 200 mg/kg body weight of CAAE. After thirty days of exposure to the diet and administration of the corresponding plant extracts, the rats were sacrificed with chloroform and the required organs were excised. The hematological indices, as well as function indicators and levels of drug metabolizing enzymes in the liver and kidney, were investigated with standard protocols. The results indicated that the hematological parameters and kidney and liver function indices were altered in rats fed with crude oil contaminated diet. However, the values came close to those in control rats when Costus afer aqueous extracts were administered. Similarly, the activities of oxidase enzymes (aldehyde oxidase, monoamine oxidase, xanthine oxidase, and sulphite oxidase), following their inhibition by the ingestion of crude oil contaminated diet, equally restored close to control values upon treatment with Costus afer aqueous extract. This study, therefore, was able to establish an aqueous extract of Costus aferleave as an antidote for crude oil intoxication. 


Author(s):  
Christopher R. Wellaway ◽  
Ian R. Baldwin ◽  
Paul Bamborough ◽  
Daniel Barker ◽  
Michelle A. Bartholomew ◽  
...  

2021 ◽  
pp. DMD-AR-2021-000665
Author(s):  
Daigo Asano ◽  
Syoya Hamaue ◽  
Hamim Zahir ◽  
Hideyuki Shiozawa ◽  
Yumi Nishiya ◽  
...  

Insects ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1062
Author(s):  
Qing-Hai Wang ◽  
Xing Gao ◽  
Hong-Song Yu ◽  
Ze Zhang ◽  
Quan-You Yu

Sex pheromones are vital to sexual communication and reproduction in insects. Although some key enzymes in pheromone production have been well studied, information on genes involved in the terminal pathway is limited. The domestic silkworm employs a pheromone blend containing (E,Z)-10,12-hexadecadienol (bombykol) and analogous (E,Z)-10,12-hexadecadienal (bombykal); whereas, its wild ancestor B. mandarina uses only bombykol. The two closely related moths might be a good model for exploring the genes involved in aldehyde pheromone synthesis and metabolism. By deep sequencing and analyzing the sex pheromone gland (PG) transcriptomes; we identified 116 candidate genes that may be related to pheromone biosynthesis, metabolism, and chemoreception. Spatiotemporal expression profiles and differentially expressed analysis revealed that four alcohol oxidases (BmorAO1; 2; 3; and 4); one aldehyde reductase (BmorAR1); and one aldehyde oxidase (BmorAOX5) might be involved in the terminal pathway. Phylogenetic analysis showed that, except for BmorAO3 and MsexAO3, AOs did not show a conversed orthologous relationship among moths; whereas, ARs and AOXs were phylogenetically conserved. This study provides crucial candidates for further functional elucidation, and which may be utilized as potential targets to disrupt sexual communication in other moth pests.


2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi79-vi79
Author(s):  
wei zhong ◽  
Lily Liu ◽  
Claire Sun ◽  
Zhihua Mu

Abstract ATM (ataxia telangiectasia mutated) kinase, activated by DNA double-strand breaks, promotes DNA repair as well as activates DNA damage checkpoint and plays a key role for resistance to radiotherapy and chemotherapy. ATM function loss confers hypersensitivity to ionizing radiation evidenced by ataxia-telangiectasia (A-T) cells. Thus, pharmacological inhibition of ATM kinase is expected to suppress DSB DNA repair, block checkpoint controls and enhance the therapeutic effect of radiotherapy and other DNA double-strand breaks-inducing chemotherapy. Herein, we report a discovery of a potent, selective, orally bioavailable, and brain penetrable ATM inhibitor WSD0628, as a radiosensitizer for GBM and metastatic CNS tumors with IC50 against ATM < 1nM with high selectivity ( >400 folds) for ATR and DNA-PK. WSD0628 is highly selective over other kinases. In-vitro MDCKII transfected cells and Caco-2 assays have shown that WSD0628 is highly permeable and not a substrate of P-gp or BCRP, two main efflux transporters expressed on human BBB. Preclinical CNS PK studies in rat and mouse confirmed good brain penetration of WSD0628 with Kp,uu,brain and Kp,uu,csf > 0.3. Significant prolongation of overall survival for mice bearing GBM PDX intracranial model was achieved by treatment with WSD0628 (5mpk, QD) combo with radiation. Moreover, WSD0628 shows low PK variation liability without aldehyde oxidase (AO) metabolism, low hERG liability ( >30 uM), and good safety window based on DRF studies. Taken together, our data provide a good rationale for WSD0628 to be developed toward clinic combo with radiation for the treatment of patients with GBM and cancers with CNS metastasis.


Author(s):  
Naoki Takaoka ◽  
Seigo Sanoh ◽  
Shigeru Ohta ◽  
Mariam Esmaeeli ◽  
Silke Leimkühler ◽  
...  

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1707
Author(s):  
Zoe Coombes ◽  
Katie Plant ◽  
Cristina Freire ◽  
Abdul W. Basit ◽  
Philip Butler ◽  
...  

Following oral administration, the bioavailability of progesterone is low and highly variable. As a result, no clinically relevant, natural progesterone oral formulation is available. After oral delivery, first-pass metabolism initially occurs in the intestines; however, very little information on progesterone metabolism in this organ currently exists. The aim of this study is to investigate the contributions of liver and intestine to progesterone clearance. In the presence of NADPH, a rapid clearance of progesterone was observed in human and rat liver samples (t1/2 2.7 and 2.72 min, respectively). The rate of progesterone depletion in intestine was statistically similar between rat and human (t1/2 197.6 min in rat and 157.2 min in human). However, in the absence of NADPH, progesterone was depleted at a significantly lower rate in rat intestine compared to human. The roles of aldo keto reductases (AKR), xanthine oxidase (XAO) and aldehyde oxidase (AOX) in progesterone metabolism were also investigated. The rate of progesterone depletion was found to be significantly reduced by AKR1C, 1D1 and 1B1 in human liver and by AKR1B1 in human intestine. The inhibition of AOX also caused a significant reduction in progesterone degradation in human liver, whereas no change was observed in the presence of an XAO inhibitor. Understanding the kinetics of intestinal as well as liver metabolism is important for the future development of progesterone oral formulations. This novel information can inform decisions on the development of targeted formulations and help predict dosage regimens.


Author(s):  
D.S. Tokasheva ◽  
Zh.A. Nurbekova ◽  
A.Zh. Akbassova ◽  
R.T. Omarov

Molybdenum is a key microelement in plant vital functioning. The microelement can be absorbed by the plants only in the form of molybdate-anion.  The Molybdenum deficiency affects negatively to the most important agricultural growing.  As molybdenum takes part in such vital mechanisms as nitrogen and sulfur metabolism, plant hormone biosynthesis, and purine banding catabolism. Molybdenum is included in enzyme content which is called molybdoenzyms. Having bonded with molybdopterin it creates molybdenum co-factor (Moco) and gets oxidation-reduction properties. Moco is included in active site of molybdoenzymes. They take part in sulfur and nitrogen metabolism, and detrimental compound detoxication. Molybdenum deficiency is characterized by the slow plant growth, low amount of chlorophyll ascorbic acid capacity.It was noticed that plants suffering from the molybdenum deficiency can be saved, sodium molibdate can be used, it can be put directly in the soil or plant leaves can sprayed with the solution. There are five plant molibdoenzymes which are currently known: sulfite oxidase (SO), xanthine dehydrogenase (XD), nitrate reductase (NR), aldehyde oxidase (AO) and mitochondrial amidoxim-regenerative component. Nitrate reductase catalyzes the first stage of nitrate assimilation, eucariotic organisms contain three isoforms of the molybdoezimes: A NADH, A NAD(P)H и NADPH.  Xanthine dehydrogenase regulates purine metabolism. XD increases plant antioxidant ability and slows down leaves aging. Molybdoenzymess are involved in the process of the stress adaptation, defining of the mechanisms and their reaction to environmental stress conditions is important for plant stress resistance.


2021 ◽  
Author(s):  
Zhadyrassyn Nurbekova ◽  
Sudhakar Srivastava ◽  
Dominic Standing ◽  
Assylay Kurmanbayeva ◽  
Aizat Bekturova ◽  
...  
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Author(s):  
Cristiano Mota ◽  
Ana Diniz ◽  
Catarina Coelho ◽  
Teresa Santos-Silva ◽  
Mariam Esmaeeli ◽  
...  

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