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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
Sat Dec 11 2021
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Ameliorative Effects of the Aqueous Extract of Allium porrum (Wild Leek) against Cisplatin-Induced Nephrotoxicity in Rabbits
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The aim of the present study was to investigate the nephroprotective, hypolipidemic and hypoglycemic effects of Allium porrum (leek) in rabbits with cisplatin nephrotoxicity. Forty adult male New Zealand rabbits were divided randomly into four groups (ten rabbits in each group) as follows: Group I: (negative control) (C) received oral daily dose of distilled water for 15 successive days. Groups II: (Leek) (L) received oral daily dose of aqueous leek extract (500mg/kg/day) for 15 successive days. Group III: (positive control) [cisplatin (CP)] received oral daily dose of distilled water for 15 successive days, and subsequently administered single dose of Cisplatin (3.5mg/kg/day) by intraperitoneal injection from day 10 for five da

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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)
Possible Effects of Vitamin D3 and Levofloxacin on Selected Hematology Parameter of Rats
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Vitamin D is a fat-soluble vitamin with antioxidant and DNA protecting properties , Levofloxacin is a member of the fluoroquinolone drug class, Its broad-spectrum bactericidal effect affects both Gram-positive and Gram-negative bacteria.

The goal of the study is to analyze the haematology analysis in rats received levofloxacin and show the preventive impact of vitamin D3 by analyzing the haematology parameters: packed cell volume (PCV), mean corpuscular hemoglobin concentration(MCHC),haemoglobin (HB), red blood cell (RBC), mean corpuscular volume (MCV),meancorpuscular haemoglobin(MCH), WBC ,differential WBC, and Platelets.

The study included 42 rats divided into 6 groups each group 7 rats. group I negative control

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Publication Date
Fri Nov 03 2023
Journal Name
Iraqi Journal Of Pharmaceutical Sciences( P-issn 1683 - 3597 E-issn 2521 - 3512)
Possible Protective Anticancer effect of Ethanol Fraction of Iraqi Hibiscus Tiliaceus L. Leaves Extract on Diethylnitrosamine-induced Hepatocarcinogenesis in Male Rats
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Abstract  Liver cancer with hepatocellular carcinoma a serious clinical illness that progresses quickly and has a bad prognosis because to increased malignancy. Fibrosis is the precursor of liver cancer, which progresses to cirrhosis and carcinoma Diethylnitrosamine (DEN) is a chemical molecule that has been used as a carcinogenic agent to promote cancer in test animals because of its strong carcinogenic potential. Herbal plants have long been used as inexpensive, effective alternatives to pharmaceuticals in various liver-associated complications, since they contain many bioactive compounds useful in liver disorders. Hibiscus tiliaceus L. (Malvaceae) contain various phytochemicals in the plant extracts such as Flavonoids, phe

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Publication Date
Sat Jun 01 2013
Journal Name
Al Mustansiriyah Journal Of Pharmaceutical Sciences
The influence of different concentrations of aqueous green tea extract on methotrexate induced haematological toxicity in rats
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Methotrexate (MTX), a folic acid antagonist is widely used for the treatment of a variety of tumors. In the present study, the possible protective effect of aqueous green tea extract (AGTE) in methotrexate-induced haematotoxicity was investigated.Four main groups of white Albino rats were used: control group, (MTX) group, following a single dose of MTX (20 mg/kg, i.p.) saline was administered for 5 days. (AGTE) group, was treated with 1.25% concentration of AGTE only for 12 days and the (MTX+AGTE) group, in thism group rats received different concentrations of AGTE (0.625, 1.25 and 2.5%), as their sole source of drinking water, 7days before and 5 days after MTX treatment. MTX induced significant decreases in RBC, Hb, Hct, WBC and pl

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Publication Date
Thu Dec 06 2018
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Effects of Vitamin E and Q10 Supplementation against Doxorubicin-Induced Neurotoxicity in Rats
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Publication Date
Fri Jan 19 2024
Journal Name
Journal Of Complementary And Integrative Medicine
Possible protective anticancer effect of chloroform fraction of Iraqi <i>Hibiscus tiliaceus L.</i> leaves extract on diethylnitrosamine-induced hepatocarcinogenesis in male rats
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Abstract<sec id="j_jcim-2023-0290_abs_001"> <title>Objective

We aimed to examine the potential protective effects of Iraqi H. tiliaceus L. chloroform leaves extract on DEN-induced HCC in male Wistar Albino rats.

Method

Rats were assigned to four groups, six in each group. Group I: rats were administered a daily oral dose of 1 mL/kg/day of distilled water. Group II: rats were intraperitoneally injected with 70 mg/kg DEN once per week for 10 conse

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Publication Date
Mon Dec 20 2021
Journal Name
Natural Volatiles & Essential Oils
Therapeutic Effects of Allicin against the Diabetes Mellitus Induced by Streptozotocin in Male Rats
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This study aimed to see how allicin (45mg/kg BW) affected diabetic Mellitus in male rats (DM). Forty male rats were utilized, and they were split into four groups at random for 42 days. T2 was treated with 45 mg/kg B.W of allicin dissolved in 1 ml of D.W daily and injected with a single dose of sodium citrate buffer (0.5ml Intra-Peritoneal IP), DM was induced in T1 and T2 by injection of a single dose of streptozotocin 50 mg/kg B.W IP, T1 was assigned as a positive control, T3 received 45 mg/kg B.W. of allicin dissolved in 1 ml D.W. every day, and a single dose of sodium citrate buffer was injected (0.5ml IP). When diabetic rats treated with allicin in T2 were compared to diabetic rats in T1, the findings indicated a significant increase (P

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Publication Date
Wed May 31 2023
Journal Name
Research Journal Of Pharmacy And Technology
Renoprotective effects of Guggulsterone against Cisplatin-Induced Kidney Damage in White Female Albino Rats
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Background: Gugglusterone has been reported to provide protection against inflammatory and oxidative reactions of different pathological conditions. Objectives: The main object of this research work is to evaluate the renoprotective effects of guggulsterone in the prevention of cisplatin-induced nephrotoxicity in rats via assessment of renal function and histological study. Materials and methods: Rats in this study were split into four groups which comprise a control group, an induction group, a third group receiving low-dose guggulsterone, and a fourth group receiving high-dose guggulsterone. Results: a single dose of cisplatin drug has jeopardisedrenal physiology that has been demonstrated in histopathology sections and elevation

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Publication Date
Tue Jun 25 2024
Journal Name
African Journal Of Biological Sciences
Toxic effect of Thiamethoxam and Lambda cyhalothrin on Nephrotoxicity and Hematological in rats
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Thiamethoxam is a synthetic organic insecticide belong to The most significant new class of pesticides created in the last thirty years is neonicotinoids. This study's objective was to determine the effect of thiamethoxam, lambda cyhalothrin and their combination on biochemical parameters, the levels of free radicals and enzymes activities liver of male.Forty Rats ( 150-170 g ) were used. animals Were separated into four groups, each with ten rats.The Gp1 was used as control, the Gp2 was used to study the effect of thiamethoxam for 3weeks, the Gp3 was employed to examine the impact of lambda cyhalothrin for 3 weeks and the Gp4 was used to research the impact of thiamethoxam and lambda cyhalothrin for 3 weeks. thiamethoxam and/or lambda cyha

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Publication Date
Fri Sep 01 2023
Journal Name
Journal Of Medicine And Life
Potential anti-obesity effects of two-graded doses of Iraqi <i>Hibiscus tiliaceus</i> leaves extract, alone and in combination with orlistat, on high-fat diet-induced obesity in male rats
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