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.
In this research we study a variance component model, Which is the one of the most important models widely used in the analysis of the data, this model is one type of a multilevel models, and it is considered as linear models , there are three types of linear variance component models ,Fixed effect of linear variance component model, Random effect of linear variance component model and Mixed effect of linear variance component model . In this paper we will examine the model of mixed effect of linear variance component model with one –way random effect ,and the mixed model is a mixture of fixed effect and random effect in the same model, where it contains the parameter (μ) and treatment effect (τi ) which has
... Show MoreBackground: Migraine is one of multiple attack neurological conditions that causes moderate to severe headaches with no defined pathophysiology and few animal models. Aim: Establishing an animal model that reproduces migraine-like action is important in medical research to identify the mechanism underlying this disorder. Additionally, it facilitates the availability and reliability of new models that may act as human surrogate models. Method: Rabbits were divided into four groups. Negative group, migraine group, rizatriptan- nitroglycerin group, and rizatriptan group. The frequency of head scratching and the histopathological changes in the brain, liver, kidney, and heart for groups were evaluated in all groups. Results: T
... Show MoreBackground: Migraine is one of multiple attack neurological conditions that causes moderate to severe headaches with no defined pathophysiology and few animal models. Aim: Establishing an animal model that reproduces migraine-like action is important in medical research to identify the mechanism underlying this disorder. Additionally, it facilitates the availability and reliability of new models that may act as human surrogate models. Method: Rabbits were divided into four groups. Negative group, migraine group, rizatriptan- nitroglycerin group, and rizatriptan group. The frequency of head scratching and the histopathological changes in the brain, liver, kidney, and heart for groups were evaluated in all groups. Results: T
... Show MoreBackground: This in vitro study was carried out to evaluate the effects of various veneering dentin ceramic thicknesses and repeated firings on the color of lithium disilicate glass-ceramic (IPS e.max Press) and zirconium-oxide (IPS ZirCAD) all-ceramic systems, measured by clinical spectrophotometers (Easyshade Advance 4.0) . Materials and methods: The 72specimens cube-shaped have the dimension of about 11 mm in width, 14 mm in length, 1mm in thickness, these cores divided into 3 groups according to the type of material each group have (24)core specimens. Each group had been divided into three sub-groups (each having 8 specimens) according to veneering with dentin ceramic thicknesses: as 0.5, 1, or 2 mm (n=8). IPS e.max press and ZirCAD c
... Show MoreThis study has three parts, the first one is the synthesis of a novel Schiff bases by the condensation of guanine or 9-[{2-hydroxyethoxy}methyl]-9H-guanine with variety aldehydes to yield four different bases as follows: (E)-2-((4-nitrobenzylidene)amino)-1,9-dihydro-6H-purin-6-one (S1), (E)-2-((4-methoxybenzylidene)amino)-1,9-dihydro-6H-purin-6-one (S2), (E)-2-((2-hydroxybenzylidene) amino)-9-((2-hydroxy ethoxy)methyl)-1,9-dihydro-6H-purin-6-one (S3), and (E)-2-(((9-((2-hydroxy ethoxy)methyl)-6-oxo-6,9-dihydro-1H-purin-2-yl)imino)methyl)benzoic acid (S4). Then, spectroscopic analyses such as Elemental Analysis, UV/VIS, Mass spectra, FTIR, 1H,13C-NMR were made to recognize these bases. In the second part, the ability of synthesized bases to
... Show MoreTo elucidate the anti- Methicillin resistance Staphylococcus aureus (MRSA) effect of pomegranate alone and in combination with moxifloxacin fluoroquinolone. A total of five clinical isolates of MRSA (ATCC 43300) were used in the study. Disc diffusion method was used to determine the anti-MRSA effect of pomegranate and/or moxifloxacin by using Mueller-Hinton agar. Minimal inhibitory concentration (MIC), fractional inhibitory concentration (FIC) of moxifloxacin and pomegranate were calculated, the dynamic picture of the bactericidal effect of pomegranate and/or moxifloxacin was determined. SPSS version 20.00 was used for data analysis. Zone of inhibition (ZOI) of moxifloxacin was 19.67±4.84mm which was not significant compared with pomegrana
... Show MoreThe research aims at identifying the level of family violence directed against the kindergarten child, as well as to identify the significance of the difference in family violence directed against the kindergarten child according to the gender variable
(male-female). It aims also to identify the significance of the difference in family violence directed against the kindergarten child according to the Stage variable (kindergarten-pre-primary). The researcher employed the descriptive correlative approach to conduct the study. The research sample was chosen in a simple random way, as the number of the participants was (130) boys and girls, with (70) males and (60) females, distributed according to the stage with (66) participants in
... Show MoreThis investigation was carried out to estimate the antiparasitic potential of silver and Chitosan nanoparticles loaded with spiramycin against toxoplasmosis infected. After mice injected intraperitoneal in a dose 103viable tachyzoites for acute infection; then treated with spiramycin, chitosan nanoparticles and silver nanoparticles as a single or combined therapy given for seven days. Peritoneal fluid examination revealed a significant decrease in the number of