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bijps-1632
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
Sat Jan 01 2022
Journal Name
Biomed Research International
Zerumbone‐Loaded Nanostructured Lipid Carrier Gel Enhances Wound Healing in Diabetic Rats
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This study investigated the healing effects of topical application of zerumbone, a well‐known anti‐inflammatory compounds loaded on nanostructured lipid carrier gel (Carbopol 940) (ZER‐NLCG) on excisional wounds in streptozotocin‐induced diabetic rats. Diabetic rats with inflicted superficial skin wound were topically treated with ZER‐NLCG, empty NLCG, and silver sulfadiazine cream (SSDC) once daily for 21 days. Wound tissue samples were analyzed for proinflammatory cytokines, namely, interleukin‐6 (IL‐6), interleukin‐1 β (IL‐1β), and tumor necrosis factor‐α (TNF‐α), hydroxyproline contents, catalase,

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Publication Date
Wed Jan 01 2025
Journal Name
Journal Of Animal Health And Production
Resveratrol Administration Reverses the Endometriosis-Mediated Outcomes via Tgfβ Signaling in Rats
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Endometriosis (END) is a chronic inflammatory disorder marked by the existence of endometrial-like tissue in the abnormal sites, resulting in immunological and inflammatory dysregulation. This study was to examine the impact of resveratrol and the AhR antagonist, CH223191, on the modulation of inflammatory and immunological responses in an experimental rat model of endometriosis. Adult female rats and adult male rats were employed in the current study. The female rats were randomly divided into the following: Naïve rats, donor rats for endometrial tissue transplantation, recipient endometriotic rats, and fertile male rats utilized for fertility tests. All endometriotic rats were equally divided into four groups, as follows: END group: Rats

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Publication Date
Tue Mar 28 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Evaluation of Rosuvastatin Effect as Adjuvant Therapy to Methotrexate on Lipid Profile and the Possibility of its Cardioprotective Effect in Iraqi Patients with Active Rheumatoid Arthritis
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Rheumatoid arthritis (RA) is a common inflammatory disease that associated with increased morbidity and mortality due to accelerated atherosclerosis. Rosuvastatin is a unique hydroxy methyl glutaryl Co A (HMGCoA) reductase inhibitor that has anti inflammatory effects.

The aim of this study was to evaluate the effect of rosuvastatin as adjuvant therapy to methotrexate (MTX) on lipid profile and its possible cardioprotective effect in RA patients. A double blinded placebo controlled clinical trial with 8 weeks follow up periods at which 40 patients with active RA using MTX were randomized into 2 groups to receive either rosuvastatin 10mg or placebo as adjuvant therapy to MTX. In addition to twenty healthy subjects as control group.

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Publication Date
Tue Mar 28 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Bioequivalence and Pharmacokinetics of Two Formulations of Amlodipine Tablets in Healthy Subjects
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The bioequivalence of a single dose tablet containing 5 mg amlodipine as a test product in comparison to Norvasc® 5 mg tablet (Pfizer USA) as the reference product was studied. Both products were administered to twenty eight healthy male adult subjects applying  a fasting, single-dose, two-treatment, two-period, two-sequence, randomized crossover design with two weeks washout period between dosing. Twenty blood samples were withdrawn from each subject over 144 hours period. Amlodipine concentrations were determined in plasma by a validated HPLC-MS/MS method. From the plasma concentration-time data of each individual, the pharmacokinetic parameters; Cmax, Tmax, AUC0-t, AUC0-

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Publication Date
Thu Jan 30 2020
Journal Name
Journal Of Engineering
Calculation of Pressure Loss of Two Drilling Muds in Noor Oil Field
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In this work, calculation of pressure losses in circulating system for two drilling muds is evaluated in Noor oil field. Two types of drilling muds that were used for drilling section 12 1/4" and 8 3/4" which are Salt saturated mud and Ferro Chrome Lignosulfonate-Chrome Lignite mud. These calculations are based on field data that were gathered from the drilling site of well Noor-15, which are included, rheological data, flow data and specification of drill string. Based on the obtained results, the best rheological model that fit their data is the Herschel-Bulkley model according to correlation coefficient value for their two drilling mud. Also, the difference between the calculated pressure lo

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Publication Date
Fri Jun 07 2024
Journal Name
Medicine
Impact of TYMS gene polymorphism on the outcome of methotrexate treatment in a sample of Iraqi rheumatoid arthritis patients – identification of novel single nucleotide polymorphism: Cross-sectional study
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The current work aims to evaluate the association between genetic mutations in thymidylate synthetase (TYMS gene in exon1 and partial regions of promotor and intron 1 [877 bp, 657,220–658,096 bp]) and the therapeutic outcomes for rheumatoid arthritis (RA) Iraqi patients. An observational cross-sectional study involving 95 RA patients with established RA patients based on their methotrexate treatment responsiveness. Genetic sequencing of the TYMS gene was performed for all patients according to the instruction manuals of the sequencing company (Macrogen Inc. Geumchen, South Korea). Four polymorphisms were identified by sequencing 95 randomly selected patients in the noncoding region of TYMS

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Publication Date
Thu Sep 01 2011
Journal Name
Al-rafidain Dental Journal
The Effect of Two Bonding Agents Generations On Microleakage Of Composite Resin Using Two Light Curing Systems.
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Aim: To evaluate the effect of two bonding systems and two curing systems on sealing ability of class V composite restorative materials. Materials and methods: This study was performed in vitro on 40 caries free upper first premolar teeth. The Standardized class V cavity preparation on buccal and lin- gual surfaces of each tooth was done. Then the teeth were randomly divided into two major groups each of twenty. 40 cavities were performed on these teeth and the first group7th generation bonding agent (i Bond) were applied according to the manufacturer instructions and single increment of univer- sal composite (XRV Herculite) from kerr were applied and twenty of the cavities were cured with con- ventional light cure device (astralis-5) and t

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Publication Date
Sat Jan 07 2023
Journal Name
Journal Of Advanced Pharmacy Education And Research
Fimasartan attenuates edema and systemic changes in egg albumin-induced paw inflammation in rats
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Angiotensin receptor blockers are well known for their therapeutic efficacy and fimasartan has been used safely and efficiently since 2010 in the treatment of hypertension. The study aimed to examine the anti-inflammatory effect of fimasartan in egg albumin-induced inflammation in rats. Rats were treated with diclofenac (25 mg/kg, intraperitoneally) or fimasartan at two different doses (3 or 10 mg/kg, intraperitoneally). The increase in the thickness of the paw was considered to be edema, which was measured using a vernier caliper. Serum was collected to analyze the systemic production of the inflammatory mediators TNF-α, and IL-6. The results showed that fimasartan in both doses significantly reduced edema in inflamed rat paws and produce

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Publication Date
Sun Feb 03 2019
Journal Name
Journal Of The College Of Education For Women
Analysis of the clause relations in the presidential presuasion in a war against Iraq
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0

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Publication Date
Thu Aug 25 2022
Journal Name
Special Education
Speech Act of Persuasion in two Political Speeches American and British.
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BN Rashid…, Special Education, 2022

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