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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
Thu Oct 29 2020
Journal Name
Toxicological Research
Liver functions in combined models of the gentamicin induced nephrotoxicity and metabolic syndrome induced by high fat or fructose diets: a comparative study
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Publication Date
Mon Mar 27 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Design, Synthesis, Characterization and Preliminary Anticancer Study for Methotrexate Silibinin Conjugates
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The spectrum of clinical efficacy of Methotrexate (MTX) is broad in that MTX is used in the treatment of certain cancers, severe psoriasis and rheumatoid arthritis.Various mechanisms by which cancer cells grown in tissue culture become resistant to anticancer drugs. The use of multiple  drugs with different mechanisms of entry into cells and different cellular targets allows for effective chemotherapy and high cure rates. In an efforts to develop effective strategies that increase the therapeutic potential of anticancer drugs with less systemic toxicity ,are being directed  towards the investigation of dietary supplements and other phytotherapeutic agents for their synergistic efficacy in combination with anticancer drugs. A pr

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Publication Date
Mon Mar 27 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Design, Synthesis, Characterization and Preliminary Anticancer Study for Methotrexate Silibinin Conjugates
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The spectrum of clinical efficacy of Methotrexate (MTX) is broad in that MTX is used in the treatment of certain cancers, severe psoriasis and rheumatoid arthritis.Various mechanisms by which cancer cells grown in tissue culture become resistant to anticancer drugs. The use of multiple  drugs with different mechanisms of entry into cells and different cellular targets allows for effective chemotherapy and high cure rates. In an efforts to develop effective strategies that increase the therapeutic potential of anticancer drugs with less systemic toxicity ,are being directed  towards the investigation of dietary supplements and other phytotherapeutic agents for their synergistic efficacy in combination with anticancer drugs. A promi

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Publication Date
Fri Jan 01 2021
Journal Name
International Journal Of Agricultural And Statistical Sciences
COMPARISON OF SOME NONPARAMETRIC METHODS TO DETERMINE THE NUMBER OF RADIATION DOSES FOR BREAST CANCER PATIENTS
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Radiation therapy plays an important role in improving breast cancer cases, in order to obtain an appropriateestimate of radiation doses number given to the patient after tumor removal; some methods of nonparametric regression werecompared. The Kernel method was used by Nadaraya-Watson estimator to find the estimation regression function forsmoothing data based on the smoothing parameter h according to the Normal scale method (NSM), Least Squared CrossValidation method (LSCV) and Golden Rate Method (GRM). These methods were compared by simulation for samples ofthree sizes, the method (NSM) proved to be the best according to average of Mean Squares Error criterion and the method(LSCV) proved to be the best according to Average of Mean Absolu

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Publication Date
Thu May 05 2022
Journal Name
Al-kindy College Medical Journal
Possible role of Spironolactone in a sample of Iraqi patients with acute central serous chorioretinopathy: Spironolactone in acute csr
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Background: Central serous chorioretinopathy (CSCR) is an idiopathic condition aggravated by exogenous or endogenous glucocorticoids. Vascular deregulation in the choroid is a new hypothesis regarding central serous chorioretinopathy occurrence. The inhibition of choroidal mineralocorticoid receptors has a great role in shortening the duration of CSCR by inhibiting choroidal vasodilatation and leak.

Objective:  To assess the effect of oral spironolactone on subretinal fluid, central macular thickness and visual acuity in patients with acute CSCR compared to observation.

Subjects and Methods:  a hospital based, randomized clinical trial carried out at outpatient clinic in Ibn-Alhaitham Teaching E

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Publication Date
Thu Mar 30 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Evaluation of the Anti-Inflammatory Effect of Pioglitazone in Experimental Models of Inflammation in Rats
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         The antidiabetic thiozolidinediones (TZDs) a class of peroxisome proliferators-activated receptor (PPAR) ligands has recently been the focus of much interest for their possible role in regulation of inflammatory response. The present study was designed to evaluate the anti-inflammatory activity of pioglitazone in experimental models of inflammation in rats. The present study was conducted to evaluate the anti inflammatory effect of TZDs (pioglitazone 3mg/Kg) on acute, sub acute and chronic model of inflammation by using egg-albumin and formalin–induced paw edema in 72 rats, relative to reference drugs Dexamethasone 5mg/Kg and Piroxicam 5mg/Kg. In each inflammation model, 24 rats wer

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Publication Date
Thu Jul 20 2023
Journal Name
Polymers In Medicine
Effect of subinhibitory doses of rifaximin on in vitro Pseudomonas aeruginosa adherence and biofilm formation to biotic and abiotic surface models
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Publication Date
Fri Jun 16 2023
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Lipid -Lowering Effect of Polysaccharide (Pectin) of Viscum album L. Plant in Rats
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Disturbances of lipid metabolism is a predisposing factor of cardiovascular diseases, which are accompanied by high mortality rates of the population - ischemic heart disease and ischemic stroke. Plant polysaccharides can be promising remedies for correction of lipid imbalance.

In this regard, the aim of the study was to assess the hypolipidemic activity of polysaccharides isolated from the leaves of mistletoe.

The test-object was the leaves of the white mistletoe (Viscum album L.) growing on the apple (Malus domestica Borkh.), and the pear (Pyrus communis L.). Polysaccharides (water-soluble polysaccharides and pectin substances) were quantitatively determined by the gravimetric method followed

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Publication Date
Wed Oct 30 2024
Journal Name
Iraqi Journal Of Science
Evaluation of the Activity of Olibanum Oil as an Immune Booster in Rats
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The applications of herbal medicine have recently acquired growing interest in range of the prophylaxis and treatment of diseases. Olibanum has been used since ancient eras and several reports studied the pharmacological characteristics of boswellic acid, particularly their effect on the inflammatory response, analgesic properties, and anti-arthritic activity mostly in cell lines, but new approaches include animal models to assess these natural derivatives effects taking into consideration of being safer than synthetic preparations.  The impact of olibanum oil on several parameters was studied in rats during this study. These included white blood cell (WBC) count, lactate dehydrogenase (LDH), and C reactive protein (CRP), as well a

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Publication Date
Thu Nov 01 2018
Journal Name
Iraqi National Journal Of Nursing Specialties
Testing Bromocriptine Dose Necessary For Suppression of Lactation in Rats: Morphological Study
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Abstract: Objectives: The lowest dose of bromocriptine, necessary for suppression of lactation in rats, was estimated in this investigation. Methodology: Fifty healthy lactating rats were treated with different doses of bromocriptine. Cessation of lactation was assessed clinically and histologically. Results: Revealed that the lowest dose capable of lactation suppression is 4 mg bromocriptine / kg body wt. / day. It is very important to know the exact dose, which can suppress lactation in rats because these laboratory animals are commonly employed in experiments concerning this topic. Key words: Bromoci

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