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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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Tue May 01 2018
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Publication Date
Mon Sep 04 2023
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Rheumatoid arthritis (RA) is characterized by persistent joint inflammation, which is a defining feature of this chronic inflammatory condition. Considerable advancements have been made in the field of disease-modifying anti-rheumatic medicines (DMARDs), which effectively mitigate inflammation and forestall further joint deterioration. Anti-tumor necrosis factor-alpha (TNF-α) drugs, which are a class of biological DMARDs (bDMARDs), have been efficaciously employed in the treatment of RA in recent times Adalimumab, a TNF inhibitor, has demonstrated significant efficacy in reducing disease symptoms and halting disease progression in patients with RA. However, its use is associated with major side effects and high costs. In addition,

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Sat Jul 01 2017
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Groundwater quality deterioration due to anthropogenic natural activities and its immense utilization in various sectors is considered a great concern. The aim of this study is to determine the groundwater quality parameters at various sources in and around Dhaka city and compare them with Bangladesh drinking water standards. In this study, six groundwater quality parameters (pH, DO, COD, TS, TDS, and arsenic) and ten groundwater samples are analyzed to determine the water quality. The collected samples have maximum and minimum pH values of 6.9 and 6.4, respectively. Maximum and minimum DO values are 0.3 and 0.1 mg/L, respectively. The arsenic concentration is 0 mg/L for all collected groundwater samples. The maximum and minimum COD

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Tue May 27 2025
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impact of mental games on improving shooting accuracy among young basketball players in Iraqi clubs
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This study investigates the effectiveness of mental games in enhancing shooting accuracy among young basketball players. Initially, baseline shooting accuracy was assessed through tests conducted prior to a three-week intervention involving mental games. A follow-up test revealed a significant improvement in participants' shooting accuracy following the intervention. Given the noticeable differences in the new shooting scores compared to the initial assessments, a second set of pre-intervention tests was conducted. These tests reaffirmed the significant enhancement in shooting accuracy, substantiating the hypothesis that mental games positively affect performance. The findings highlight the importance of these intervention programs

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impact of mental games on improving shooting accuracy among young basketball players in Iraqi clubs
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This study investigates the effectiveness of mental games in enhancing shooting accuracy among young basketball players. Initially, baseline shooting accuracy was assessed through tests conducted prior to a three-week intervention involving mental games. A follow-up test revealed a significant improvement in participants' shooting accuracy following the intervention. Given the noticeable differences in the new shooting scores compared to the initial assessments, a second set of pre-intervention tests was conducted. These tests reaffirmed the significant enhancement in shooting accuracy, substantiating the hypothesis that mental games positively affect performance. The findings highlight the importance of these intervention programs

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