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Possible protective effects of two different doses of cyanocobalamin against methotrexate nephrotoxicity in rats
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Abstract

   Nephrotoxicity is defined as rapid deterioration in kidney functions. It arises from direct exposure to drugs or their metabolites. Methotrexate is a famous chemotherapeutic drug with anti-inflammatory and immunosuppressive properties. A high-dose methotrexate-induced renal dysfunction can be life threatening. Cyanocobalamin, one of the forms of vitamin B12, acts as a coenzyme in the conversion of homocysteine to methionine in the cytosol, and the conversion of methylmalonyl-CoA to succinyl-CoA in the mitochondrion. This study is designed to examine the effect of cyanocobalamin in two different doses each co-administered with methotrexate at 20 mg/kg induced nephrotoxicity in rats through the involvement of Nrf2/keap1 molecular mechanism in this respect. Rats utilized in this study were randomized into 4 groups (ten rats per each group); Group 1- (Control) rats intraperitoneally injected with 0.5ml normal saline once daily for 7 consecutive days. Group 2- Rats intraperitoneally injected with 0.5ml normal saline once daily for 7 consecutive days; and at day 2, a single intraperitoneal dose of methotrexate (20mg/kg) is to be injected. Group 3- Rats intraperitoneally injected with a 0.5mg/kg cyanocobalamin once daily for 7 consecutive days, and at day 2, a single intraperitoneal dose of methotrexate (20mg/kg). Group 4- Rats intraperitoneally injected with a 2mg/kg cyanocobalamin once daily for 7 consecutive days, and at day 2, a single intraperitoneal dose of methotrexate (20mg/kg). Co-administration of cyanocobalamin at doses cyanocobalamin 0.5mg/kg and 2mg/kg with methotrexate showed significant  reduction  (P<0.05) in malondialdehyde, significant elevation (P<0.05)  in reduced glutathione level, significant upregulation in  renal Nrf2 expression and significant down regulation in renal keap1 expression each compared to corresponding levels in methotrexate-only treated group. In conclusion this study demonstrated that co-administration of cyanocobalamin at two different doses with MTX resulted in attenuation of its nephrotoxicity by the utilization of selected parameters.

Keywords: Nephrotoxicity, methotrexate, cyanocobalamin, malondialdehyde, glutathione, Nrf2, Keap1.

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Publication Date
Fri Aug 02 2024
Journal Name
Engineering, Technology &amp; Applied Science Research
Effects of utilizing Crumb Rubber as Aggregate in Asphalt Mixtures
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Experts have given much attention on the use of waste in asphalt paving because of its significance from a sustainability perspective. This paper evaluated the performance properties of asphalt concrete mixes modified with Crumb Rubber (CR) as a partial replacement for two grade sizes of fine aggregate (2.36, and 0.3 mm) at six replacement rates: 0%, 2%, 4%, 6%, 8%, and 10% by weight. Asphalt concrete mixes were prepared at their Optimum Asphalt Content (OAC) and then tested for their engineering properties. Marshall properties, fatigue, rutting, ideal CT index test, Scanning Electron Microscopy (SEM), and Energy-Dispersive X-ray (EDX) spectroscopy were deployed to examine the crystalline structure and elemental composition of the C

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Publication Date
Mon Jun 19 2023
Journal Name
Journal Of Engineering
Numerical Simulation of flow in pipe with cross jet effects
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A numerical method is developed to obtain two-dimensional velocity and pressure distribution through a cylindrical pipe with cross jet flows. The method is based on solving partial differential equations for the conservation of mass and momentum by finite difference method to convert them into algebraic equations. This well-known problem is used to introduce the basic concepts of CFD including: the finite- difference mesh, the discrete nature of the numerical solution, and the dependence of the result on the mesh refinement. Staggered grid implementation of the numerical model is used. The set of algebraic equations is solved simultaneously by “SIMPLE” algorithm to obtain velocity and pressure distribution within a pipe. In order to

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Publication Date
Sun Dec 16 2018
Journal Name
Al-academy
The Aesthetics of the Digital Sound Effects in Television Drama
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The sound effects in TV dramas achievements have become very important not only in terms of function and implementation, but at a greater and wider level in terms of artistic and aesthetic values, which are produced and employed in the most important world artistic achievements of drama, using the latest and most prominent technologies and equipment and according to the expressive and dramatic values expressed by these modern digital sound effects. Therefore, the researcher chose the aesthetic effect of digital sound effects in television drama to identify the aesthetic aspects provided by digital sound effects by employing them and their accompaniment for the image.

The researcher, therefor, divided this study into the methodolo

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Publication Date
Fri Feb 12 2016
Journal Name
International Journal Of Advanced Statistics And Probability
Two fixed point theorems in generalized metric spaces
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<p>In this paper, we prove there exists a coupled fixed point for a set- valued contraction mapping defined on X× X , where X is incomplete ordered G-metric. Also, we prove the existence of a unique fixed point for single valued mapping with respect to implicit condition defined on a complete G- metric.</p>

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Publication Date
Wed Jul 01 2020
Journal Name
Medico-legal Update,
Histological and enzyme histochemical changes of liver induced by the action of maxxthor insecticide in male albino rats
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The present study aimed to investigate the histological, enzyme histochemical changes and liver function effects of Maxxthor insecticide on albino rats in liver. The experiment included 20 rat which were divided into four groups, the first group 5 rats were considered the control animals and the others were divided equally into three groups with a dose of 0.01, 0.1and 1 mg / kg of body weight, respectively for a period 40 days. The animals given each 48 hours via oral route Maxxthor by tube dosage after dissolved with distilled water. Microscopic examination of liver showed inflammatory cell aggregation around vessels, congestion and dilation of sinusoids hepatocytes hypertrophy with severs inflammatory cells infiltration, kupffer cells pro

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Publication Date
Thu Jan 01 2015
Journal Name
Iraqi Postgraduate Medical Journal
Immunohistochemical Study of Leydig Cells in the Testicular Interstitial Tissue of Rats Treated with Tribulus Terrestris Using P450scc.
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BACKGROUND: Tribulus terrestris has been commonly used in folk medicine to energize, vitalize and improve sexual function and physical performance in men and laboratory rats. OBJECTIVE: To study the effect of Tribulus terrestris on the number of Leydig cells. MATERIALS AND METHODS: Tribulus terrestris was given to mature male rats as an oral single herbal suspension in a dose of 2.0mg /1000gbody weight for 14 days to stimulate spermatogenesis. Formalin fixed paraffinembedded tissue sections were performed for histological, immunohistochemical and morphometrical studies. RESULTS: Histological study revealed wider seminiferous tubules and increased spermatocytes population with an increased sperm density inside the lumen of the tubul

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Publication Date
Mon Jun 03 2024
Journal Name
Research Journal Of Chemistry And Environment
Molecular study of two medicinal leech species
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he genus Hirudo is an invertebrate animal that got major concerns to human. However, genetics of Hirudo has been unwell considered in Iraq. In order to gain a deeper understanding in the outline of the genetic of Hirudo that were used in alternative medicine clinics, nineteen specimens of Hirudo were obtained. Fourteen of them (H.verbana, n=10; H. orientalis, n=4) were obtained from some different clinics and scientific centres in Baghdad, Iraq between January and March 2022, these specimens were considered as non-local leeches. The other (native isolates) leeches (H. orientalis, n=5) were collected in 2014 from two localities in Erbil, northern Iraq. ITS-2, COI and 12S-rRNA of Hirudo spp were amplified using conventional polymerase chain r

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Publication Date
Fri Apr 01 2022
Journal Name
Baghdad Science Journal
Comparison of Protein Concentration in Red and White Muscles in Two Species of Bony Fish
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The current study deals with estimating the protein concentration and the effect of fish weight on protein concentration values in red and white muscles in two different regions ( R1 : Anterior region lies 2 cm behind the head and R2: posterior region lies 2cm from caudal fin  (in  two types of bony fish, namely common carp (Cyprinus carpio) and Nile tilapia (Oreochromis niloticus). Samples were collected from Karmat Ali river- north of Basrah between October 2019 and February 2020. The protein was extracted using protein extraction buffer, the current study show that the average of  protein concentration in red muscles of Nile tilapia ranged between  7.74-7.4 mg / ml  and ( 6.8-8.85 mg / ml) in R1 and R2 region re

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Publication Date
Wed Apr 01 2020
Journal Name
Diyala Journal Of Medicine
Histological Evaluation of Local Application of Flavonoid Extract of Capparis Spinosa on Wound Healing in Alloxan-Induced Diabetic Rats
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Publication Date
Wed Feb 02 2022
Journal Name
Journal Of University Of Shanghai For Science And Technology
Antiparasitic activity of Artemether and combination Artemether with Artemisinin against Leishmaniasis, in vitro.
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The Leishmania donovani parasite causes visceral leishmaniasis (VL), an acute and fatal form of leishmaniasis. Because traditional therapy alternatives, such as glucantime and other pentavalent medicines, are toxic and have side effects, new treatments with fewer negative effects are needed. Only a handful of drugs are clinically beneficial to treatments of the disease, but considerable limitations threaten their very usage. Novel, safe, and efficient drugs, including those against antimalaria and leishmaniasis co-infections, are so essential. Artemether (ATM) is an Artemisinin derivative that has been demonstrated to be useful in the treatment of malaria and, more recently, leishmaniasis. The current research was carried out to evaluate th

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