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EVALUATION OF CHEMOPREVENTIVE RESPONSE OF PENTOXIPHYLLINE AND SILDENAFIL INCOLORECTAL CARCINOMA EXPERIMENTALLY INDUCEDIN RATS: COMPARATIVE STUDYWITH 5-FLUOROURACIL
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Objective: This study was designed to investigate some possible therapeutic mechanisms of pentoxifylline and sildenafil in the treatment of colorectal carcinoma induced by 1, 2 dimethylhydrazines in rats. Methods: Rats were allocated into seven groups, negative control, colon cancer induced by 1,2,dimethylhydrazine, 5-fluorouracil (5-FU) (50 mg/kg)-treated, pentoxifylline (PTX) (50 mg/kg)-treated, sildenafil (0.7 mg/kg)-treated groups; the two other groups set as colon cancer induced group treated with PTX (50 mg/kg) plus 5-FU(50 mg/kg) and sildenafil (0.7 mg/kg) plus 5-FU (50 mg/kg), respectively. Results: Biochemical results revealed significant elevation of serum carcinoembryonic antigen (CEA) levels, carbohydrate19-9 antigen (CA19-9) as colon cancer specific antigen markers; and a significant decrease in scaspase-3 (CASP3) as a marker for apoptosis, in the cancer-induced group compared to negative control group. Cancer-induced rats treated with 5-FU, with PTX or sildenafil showed a significant decrease in serum CEA and CA19-9 levels and a significant increase in CASP3 levels compared to cancer induced group. Furthermore, plasma levels of CEA and CA19-9 in 5-FU plus pentoxifylline and in 5-FUplus sildenafil groups were significantly decreased and plasma levels of CASP3 in 5-FU plus PTX, 5-FU plus sildenafil groups were significantly increased with respect to 5-FU treated group. Conclusion: Results of the present study suggest a good therapeutic approach of the PDE inhibitors, PTX and sildenafil for intervention against progressive colon cancer with special reference to the induction of apoptosis in colon cancer cells.

Publication Date
Fri Jun 16 2023
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
The Protective Effects of N-acetylcysteine against 5-Fluorouracil Induced Intestinal Toxicity in Albino Rats
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5-fluorouracil (5-FU) is a is Pyrimidine analogue widely used in the treatment of various malignancies It belongs to  the antimetabolites family that acts during the S-phase of the cell cycle thus it prevents DNA synthesis.N-acetylcysteine is nutritional complement acts as antioxidant.The purpose  of the current study is to investigate whether there is a protective  role  of N-acetylcystein against intestinal toxicity induced by 5-fluorouracil in albino rats.18 healthy adult rats were distributed into 3 groups of 6 rats for each. Group A as a control group.Group B injected with 5-FU (20 mgs dissolved in 2ml normal saline per kilogram body weight intraperitoneally for 7 successive days while Group C received N-acetylcy

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Publication Date
Sun Mar 26 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
The Possible Cardio-Protective Effects of Ethanolic Artichoke Extract against 5- Fluorouracil Induced Cardiac Toxicity in Rats
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Cardiac toxicity can occur during the therapy with several cytotoxic drugs, including 5- Fluorouracil (5- FU). It is an antimetabolite that acts during the S phase of the cell cycle and is activated by thymidine phosphorylase into fluorodeoxyuridylate (5 fluoro 2'deoxyuridine 5'monophosphate, 5-FdUMP) that inhibits thymidylate synthase, thus preventing DNA synthesis that leads to imbalanced cell growth and ultimately cell death. It is still a widely used anticancer drug, since 1957. The present study aimed to evaluate the possible cardio-protective effects of ethanolic artichoke extract (Cynara scolymus L.) against 5-fluorouracil (5-FU) induced cardio-toxicity in rats by evaluating serum levels of Alanine aminotransferase, aspartate amin

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Publication Date
Sun Dec 27 2020
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Synthesis and evaluation of B-cyclodextrin Based Nanosponges of 5- Fluorouracil by Using Ultrasound Assisted Method
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CD-nanosponges were prepared by crosslinking B-CD with diphenylcarbonate (DPC) using ultrasound assisted technique. 5-FU was incorporated with NS by freeze drying, and the phase solubility study, complexation efficiency (CE) entrapment efficiency were performed. Also, the particle morphology was studied using SEM and AFM. The in-vitro release of 5-FU from the prepared nanosponges was carried out in 0.1N HCl.

5-FU nanosponges particle size was in the nano size. The optimum formula showed a particle size of (405.46±30) nm, with a polydispersity index (PDI) (0.328±0.002) and a negative zeta potential (-18.75±1.8). Also the drug entrapment efficiency varied with the CD: DPC molar ratio from 15.6 % to 30%. The SEM an

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Publication Date
Wed Nov 01 2023
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Assessment of ellagic acid action in 5-fluorouracil induced intestinal mucositis: Assessment of ellagic acid action in 5-fluorouracil induced intestinal mucositis
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The intestinal mucositis define as inflammation and ulceration in the gastrointestinal tract wall and in some case in the oral cavity these cause by treatment with antineoplastic drug like 5-fluorouracil and Irinotecan and other types of chemotherapeutics drugs , 5-Fluorouracil-induced intestinal mucositis (IM) is consider as one of the more common tumor issue .it cause series of undesirables symptoms like severe diarrhea ,abdominal pain , stomach uncomfortable and other. The aim of this current study to see how ellagic acid act to  Attenuates 5-FU-Induced Intestinal Mucositis and  Diarrhea in Mice . we induced the intestinal mucositis by injected the mice intraperitoneally in 5-fluorouracil about 50mg per kg daily for

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Publication Date
Mon Jan 01 2024
Journal Name
Current Research In Pharmacology And Drug Discovery
Hepatoprotective effect of Nobiletin against 5-fluorouracil induce hepatotoxicity
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5-florouracil is a widely used anticancer/anti-metabolite drug used to treat solid tumor like colon cancer, head and neck, rectum, stomach, pancreas and breast cancer; but, it can cause hepatotoxicity by induction of apoptosis through activation of caspases enzymes and oxidative stress. Nobiletin is a citrus fruit-derived flavonoid that possess significant biological activity, including anticancer, and anti-inflammatory. This study was design to investigate the effects of nobiletin against 5-florouracil-indcued hepatotoxicity in male rats through the measurement of selected -inflammatory, -apoptosis, and -oxidative stress markers. By use male Albino rats weighing 150-250gm around 28 animals; giving them tap water ad libitum and fed commerci

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Publication Date
Sun Mar 04 2012
Journal Name
Baghdad Science Journal
Evaluation of cellular immune response in Golden Hamsters experimentally infected with Leishmania donovani comparing with cellular immune response against chicken Red Blood Cells.
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The Evaluation of the immune response in Golden Hamsters experimentally infected with Leishmania donovani was determined in this study, particularly, the cellular immune response. Follow up has maintained to determine the Delayed Type of Hypersensitivity using skin test both in infected and control lab animals. Chicken red blood cells were used as a parameter to evaluate the immune system; they are dull and have the ability of immunization. Two concentrations of chicken R.B.C were examined to determine which gives the higher titration in Hamsters and those were 1.5 X 109 cell/ml and 3 X 109 cell/ml , the second concentration gave the maximum titration where then used in this work. After sensitization with Chicken R.B.C for both infected a

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Publication Date
Sun Mar 04 2012
Journal Name
Baghdad Science Journal
Evaluation of cellular immune response in Golden Hamsters experimentally infected with Leishmania donovani comparing with cellular immune response against chicken Red Blood Cells.
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The Evaluation of the immune response in Golden Hamsters experimentally infected with Leishmania donovani was determined in this study, particularly, the cellular immune response. Follow up has maintained to determine the Delayed Type of Hypersensitivity using skin test both in infected and control lab animals. Chicken red blood cells were used as a parameter to evaluate the immune system; they are dull and have the ability of immunization. Two concentrations of chicken R.B.C were examined to determine which gives the higher titration in Hamsters and those were 1.5 X 109 cell/ml and 3 X 109 cell/ml , the second concentration gave the maximum titration where then used in this work. After sensitization with Chicken R.B.C for both in

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Publication Date
Mon May 01 2023
Journal Name
Journal Of Medicine And Life
Mucoprotective effect of ellagic acid in 5 fluorouracil-induced intestinal mucositis model
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Publication Date
Sun Mar 26 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Design, Synthesis and Kinetic Study of Coumarin-Based Mutual Prodrug of 5-Fluorouracil and Dichloroacetic acid
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On the basis of known coumarin-based prodrug system, a novel coumarin-based mutual prodrug of 5-fluorouracil and dichloroacetic acid was designed, synthesized and evaluated as a promising oral chemotherapeutic agent basing on in vitro stability study in HCl buffer (pH 1.2) and in phosphate buffer (pH 7.4), as well as in vitro release study in human serum. The chemical structure of prodrug was confirmed by analyzing its FTIR, 1H NMR, 13C NMR and MS-ESI spectra. The results of in vitro kinetic study indicated that the prodrug was significantly stable in HCl and in phosphate buffers, and was hydrolyzed in human serum followed pseudo first order kinetics.

Keywords: Coumarin-bas

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Publication Date
Tue Feb 01 2022
Journal Name
Macromolecular Symposia
Synthesis of 5‐Fluorouracil–Naproxen Conjugates as a Mutual Prodrug for Targeting Cancer Tissues
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Abstract<p>A new 5‐fluorouracil–naproxen conjugate is synthesized as a mutual prodrug for targeting cancer tissues. The structure of the target compound and their intermediate are characterized by their melting point, IR, <sup>1</sup>H NMR, <sup>13</sup>C NMR, and elemental microanalysis. The cytotoxic activity is preliminarily evaluated using nonsmall lung cancer CRL‐2049, human breast cancer CAL‐51, and one type of normal cell line; rat embryo fibroblast cell line. The synthesized compound shows a good cytotoxic effect at the cancer cell and no significant effect at rat embryo fibroblast cell line.</p>
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