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.
The purpose of this research work is to synthesize conjugates of some NSAIDs with sulfamethoxazole as possible mutual prodrugs to overcome the local gastric irritation of NSAID with free carboxyl group by formation of ester linkage that supposed to remain intact in stomach and may hydrolyze in intestine chemically or enzymatically; in addition to that attempting to target the synthesized derivative to the colon by formation of azo group that undergo reduction only by colonic bacterial azo reductaze enzyme to liberate the parent compound to act locally (treatment of inflammation and infections in colon).
Key words: Mutual prodrug, Ester linkage, Azo bond, Colon targeting
The purpose of this research work is to synthesize conjugates of some NSAIDs with sulfamethoxazole as possible mutual prodrugs to overcome the local gastric irritation of NSAID with free carboxyl group by formation of ester linkage that supposed to remain intact in stomach and may hydrolyze in intestine chemically or enzymatically; in addition to that attempting to target the synthesized derivative to the colon by formation of azo group that undergo reduction only by colonic bacterial azo reductaze enzyme to liberate the parent compound to act locally (treatment of inflammation and infections in colon)
The analysis, behavior of two-phase flow incompressible fluid in T-juction is done by using "A Computational Fluid Dynamic (CFD) model" that application division of different in industries. The level set method was based in “Finite Element method”. In our search the behavior of two phase flow (oil and water) was studed. The two-phase flow is taken to simulate by using comsol software 4.3. The multivariable was studying such as velocity distribution, share rate, pressure and the fraction of volume at various times. The velocity was employed at the inlet (0.2633, 0.1316, 0.0547 and 0.0283 m/s) for water and (0.1316 m/s) for oil, over and above the pressure set at outlet as a boundary condition. It was observed through the program
... Show MoreBackground: Prosthodontists estimated the parallelism of the occlusal plane to different anatomical landmarks, which was somewhat arbitrary and depended mainly on their vision. The aim of this research was to assess the degree of accuracy of prosthodontists in determining the parallelism of two lines. This research was aimed to assess which technique would be more accurate for the prosthodontist to distinguish parallelism; the comparison of the occlusal plane with the interpupillary line or with the inferior border of the earlobes. Materials and methods: Twenty eight prosthodontic specialists were included in this research. Illustrations of two lines with different tilts were presented to the participants to distinguish whether parallel or
... Show MoreThis study has applied the theoretical framework of conceptual metaphor theory to the analysis of the source and target domains of metaphors that are used in two English nineteenth century sonnets, both written by contemporaneous female poets. The quantitative and qualitative results of the textual analysis have clearly revealed that Elizabeth Barrett Browning’s sonnet 23 centres around the conceptual mapping of the journey of love and life with that of possession. In contrast, Christina Rossetti’s sonnet Remember tackles the central conceptual mapping of death as a journey in relation to its further experiential connections. In addition, the application of conceptual metaphor theory in identifying the frequencies and densities of metap
... Show MoreThe Cassia glauca Lam. is the tree that belongs to the Fabaceae family and is native to India has many uses in indigenous systems of medicine, folk medicine, and traditional Brazilian medicine. Has many pharmacological activities such as anti-diabetic, antibacterial, antifungal, antioxidant, anti-hemolytic, anticancer, cardio-protective, and Hepato-protection. The aim of study is to Isolation, identification, and quantification of some compounds from aerial parts of Cassia glauca since no phytochemical investigation had previously been done in Iraq for this plant. The aerial parts were defatted in n. hexane for 48 hours. The defatted materials were extracted in 85% ethanol using the hot method (soxhlet), then the extract was fra
... Show MoreThe present paper attempts to establish a distinction between Exochomus negripennis (Er.) and E. quadripustulatus L., depending on the characters of femoral line, male genitalia and spermatheca.
One and two-dimensional hydraulic models simulations are important to specify the hydraulic characteristics of unsteady flow in Al-Gharraf River in order to define the locations that facing problems and suggesting the necessary treatments. The reach in the present study is 58200m long and lies between Kut and Hai Cities. Both numerical models were simulated using HEC-RAS software, 5.0.4, with flow rates ranging from 100 to 350 m3/s. Multi-scenarios of gates openings of Hai Regulator were applied. While the openings of Al-Gharraf Head Regulator were ranged between 60cm to fully opened. The suitable manning roughness for the unsteady state was
... Show More