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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
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
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
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
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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Doxorubicin (DOX) is a chemotherapeutic agent; it is widely used in human malignancies. Its long-term use can cause neurobiological side-effects. Vitamin E and Coenzyme Q10may possess neuroprotective effects. This work was designed to investigate the effect of vitamin E and the coenzyme Q10(CoQ10) supplementation on neurotoxicity induced by doxorubicin(DOX) in rats. Forty nine adult rats of both sexes were used in this study; the animals were randomly enrolled into seven groups of 7 rats each. Group I: negative control (rats administered corn oil); Group II: Vitamin E at a dose of 100mg/kg/d for 3 weeks ; Group III: CoQ10 at a dose of 50 mg/kg/d for 3 weeks; Group IV: positive control (Doxorubicin 2

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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
Thu Jan 12 2023
Journal Name
Iraqi Journal Of Pharmaceutical Sciences
The Protective Effect of Omega-7 on Cisplatin-Induced Nephrotoxicity in Rat Model
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Omega-7 is a monounsaturated fatty acid that has a number of beneficial effects. Cisplatin, an effective antineoplastic agent is commonly used to treat solid tumors. Cisplatin΄s clinical use is limited due to its nephrotoxicity. Nephrotoxicity induced by Cisplatin is thought to be linked with increased formation of reactive oxygen species. The purpose of this study was to evaluate the anti-oxidant effect of omega-7 against cisplatin-induced nephrotoxicity. Thirty male wistar rats were divided randomly into five groups (six rats in each group), group 1 rats received liquid paraffin solution orally for 7 consecutive days, group 2 rats received liquid paraffin solution orally for 7 consecutive days then received single cisplatin intraperitone

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Publication Date
Sat Jul 05 2025
Journal Name
Journal Of Research In Pharmacy
Evaluation of the anti-inflammatory effect of chromium picolinate in methotrexate induced nephrotoxicity rat model
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Methotrexate is a folate antimetabolite chemical used to treat many forms of cancer and cleared mainly by kidney which result in a nephrotoxicity as a major complication of methotrexate. Trivalent chromium complex, chromium picolinate (CrPic), is mostly utilized to regulate glucose and raise insulin sensitivity—particularly in diabetes. The objective of this study was to assess the renoprotective effects of Chromium in mitigating nephrotoxicity induced by Methotrexate in rats. Study conducted on 32 male rats divided into 4 groups; Group I (Control group) in which rats received distilled water orally for 8 days, Group II (Induction group) which received a single intraperitoneal injection of Methotrexate (20 mg/kg) on

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Publication Date
Fri May 01 2026
Journal Name
Naunyn-schmiedeberg's Archives Of Pharmacology
Possible protective effects of tirzepatide on polycystic ovary syndrome in female rat model induced by testosterone propionate in comparison to metformin
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Polycystic ovary syndrome (PCOS) is a complex endocrine–metabolic disorder characterized by hyperandrogenism, ovulatory dysfunction, insulin resistance, and chronic inflammation resulting in reproductive and metabolic complications. Traditional metformin therapy improves insulin sensitivity, while newer dual incretin agonists, such as tirzepatide, may offer broader metabolic and ovarian protection. The objective of this study is to investigate whether tirzepatide could alter hormonal parameters, metabolism, inflammation, and histopathology of a testosterone propionate–induced PCOS rat model compared with metformin. Thirty prepubertal female Wistar rats were divided into five groups (n = 6). PCOS was induced by testosterone propionate (1

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