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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
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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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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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
Wed Jun 30 2010
Journal Name
Al-kindy College Medical Journal
Comparative study of the renoprotective effects of captopril and aminophylline against cainst cisplatin – induced nephrotoxicty in rats
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Background: Cisplatin is one of the most
commonly used anti-cancer drugs , but its
clinical use was limited by its nephrotoxicity .
Methods: In this study we try to investigate the
renoprotective effect of captopril and
aminophylline against cisplatin induced
nephrotoxicity .For this purpose a 36 Sprague
Dawley rats was divided randomly to 6 groups ,
each group consist of 6 rats. The first group
given normal saline and act as control group,
while the other 5 groups given cisplatin ( 7.5
mg/kg ) , captopril ( 60 mg/kg ) , aminophylline
( 24 mg/kg ) , captopril with cisplatin and
aminophylline with cisplatin respectively. All
drugs are given as single dose through
intraperitonial route. After 6

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Publication Date
Thu May 01 2025
Journal Name
Veterinary World
Aryl hydrocarbon receptor signaling in male fertility: Protective role of resveratrol and disruptive effects of CH223191 in adult male rats
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Background and Aim: The aryl hydrocarbon receptor (AhR) plays a pivotal role in spermatogenesis through its regulatory functions in redox balance and gene expression. This study aimed to investigate the effects of resveratrol (RES), a polyphenolic AhR modulator, and CH223191, a selective AhR antagonist, on male reproductive function in rats by assessing sperm quality, oxidative stress, testicular histopathology, and AhR gene expression. Materials and Methods: Forty adult male rats were randomly divided into four groups: (i) Control, (ii) dimethyl sulfoxide (vehicle), (iii) RES (100 mg/kg i.p., twice weekly), and (iv) AhR⁻ (CH223191, 10 mg/kg i.p., twice weekly), treated for 60 days. Post-treatment, sperm motility, survival, viabi

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Publication Date
Sun Jan 01 2023
Journal Name
International Journal Of Drug Delivery Technology
Protective Effects of Aqueous Cranberry Fruit Extract against Genotoxicity Induced by Cisplatin in Mice Bone Marrow Cells
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The cranberry (Vaccinium macrocarpon) is a North American native fruit and contains a very wide variety of phytochemicals, which has several beneficial effects on humans. Aim: The study was designed to assess the protective effect of cranberry fruit extract on selected genotoxic parameters induced by cisplatin in mice’s bone marrow. Methods: 56 male albino mice were randomLy divided into two equal numbers (28 mice) for each part of the study [Part one: for the evaluation of chromosomal aberrations and the mitotic index; and Part two: for the evaluation of micronucleus index]; and for each part, mice were randomly divided into 4 groups: Group I [negative Control/orally-administered normal saline]; Group II [Orally-administered cranberry fr

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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)
Impact of Different Doses of Nicorandil-Induced Ulceration (Oral , Gastrointestinal Tract, and Anal) in Rats: Roles of Leptin and Prostaglandin E2
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Many reports confirm ulcers as an adverse effect of drugs such as nicorandil and aspirin. The exact responsible mechanisms of ulceration have until now not proved. Mucosal ulcers associated with the onset of ulcer are manifested by an increase in proinflammatory cytokine, excessive prostaglandin, and up-regulation of Endothilin-1 level, which directly impacts the release of leptin. These, released locally within mucosal tissues, have played a role in controlling the extent of local inflammatory responses and processes of mucosal repair.
This study was designed to find out the correlation of plasma leptin and prostaglandin levels as a possible mechanism of oral ulcer formation as an adverse effect of nicorandil. The effect of nicorandi

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Publication Date
Sun Jun 09 2019
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Synthesis and Preliminary Anticancer Evaluation of 6-Mercaptopurine –Methotrexate Conjugate as Possible Mutual Prodrug
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Small molecules drug conjugate mutual prodrug design  (SMDC) composed of folate and lethal agent conjugate, rigidly bonded via hydrophilic bridge and self immolative disulfide  bond   ;  represent new interesting approaches for cancer treatment , the component of SMDC intended  for targeting    folate receptor , along with greater conservation  of component until reaching  the target tumor tissue . The  designing and synthesis of compound VI and VIII derived from 6-Mercaptopurine (6-MP) and Methotrexate ( MTX) conjugate altogether as mutual prodrugs were  processed forward  successfully by multistep reaction  procedures , and by Thin Layer Chromatography (TLC) for

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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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