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bijps-1632
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
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
Thu Oct 08 2020
Journal Name
British Journal Of Pharmacology
Protective effects of Δ<sup>9</sup>‐tetrahydrocannabinol against enterotoxin‐induced acute respiratory distress syndrome are mediated by modulation of microbiota
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Background and Purpose

Staphylococcal enterotoxin‐B (SEB) is one of the most potent bacterial superantigens that exerts profound toxic effects by inducing a cytokine storm. Inhaled SEB can cause acute respiratory distress syndrome (ARDS), which is often fatal and with no effective treatments.

Experimental Approach

Efficacy of Δ9‐tetrahydrocannabinol (THC) was tested in a mouse model of SEB‐mediated ARDS, in which lung inflammation, alterations in gut/lung microbiota and production of short‐chain fatty acids (SCFAs) was measured. Gene dysregulation of lung epithelial cells was studied by transcriptome arrays. F

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Publication Date
Sat Mar 25 2023
Journal Name
International Journal Of Drug Delivery Technology
The Protective Eff ect of Cinnamic Acid against Ulcerative Colitis in Mice
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Objective: To study the protective eff ects of cinnamic acid on dextran sodium sulfate (DSS) induced ulcerative colitis (UC) in mice. Materials and methods. Forty adult male mice were randomLy divided into fi ve groups, control group, an induction group received 3% DSS in drinking water for 7 consecutive days. Two treatment groups received oral suspension of cinnamic acid 50 and 25 mg/kg, respectively and 3% DSS in drinking water, for 7 consecutive days. The fi nal group received oral suspension of cinnamic acid 50 mg/kg for the latter 7 days without DSS in drinking water. All the animals were euthanized on day eight. The colon of animals was extracted and divided into two sections, the middle was homogenized and biochemically analy

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Publication Date
Thu Jun 25 2020
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Evaluation of the Possible Immuno-Protective Effect of Nigella Sativa Seed Oil on Cyclophosphamide- Induced Myelosuppression in Mice
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Myelosuppression is one of the serious adverse effects of cancer chemotherapy that lead to life threatening febrile neutropenia and considered a limiting factor for successful therapy. Cyclophosphamide a widely used anticancer drugs, induces severe bone marrow suppression by damaging hematopoietic stem cells. As cancer incidence expands globally, the demand for an effective myeloprotective therapy during cancer treatment is also increasing.Nigella sativa seed oil, a well-known plant extract that widely used for various health conditions. This study aims to evaluate the myeloprotective activity of Nigella sativa seed oil in cyclophosphamide-induced myelosuppression mice model. Myelosuppression induced by single intraperitoneal injection o

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Publication Date
Thu Mar 30 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Therapeutic Effects of Melatonin in Lead-Induced Toxicity in Rats
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           Exposure to lead results in significant accumulation in most of vital organs, and free radical damage has been proposed as a cause of lead-induced tissue damage, where oxidative stress is a likely molecular mechanism. This study was designed to evaluate therapeutic effects of melatonin in lead-induced organ toxicity in rats. The therapeutic effects of melatonin on lead induced toxicity in rats were evaluated using 36 rats, which were allocated into 3 groups and treated as follows: Group I, includes 12 rats injected subcutaneously with 0.2 ml physiological saline for 30 days, followed by treatment with a daily dose of 20mg/kg melatonin, administrated I.P for the successive 30 da

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Publication Date
Sun Dec 31 2023
Journal Name
Iraqi Journal Of Pharmaceutical Sciences( P-issn 1683 - 3597 E-issn 2521 - 3512)
Evaluation of The Genoprotective Effect of Curcumin Against Methotrexate in Bone Marrow and Spleen Cells in Mice
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Curcumin is a yellow pigment produced from the rhizomes of the Curcuma longa plant and a primary chemo preventive component of turmeric is used as a spice and food coloring ingredient. Curcumin has a large number of pharmacological activities, such as anticancer, anti-diabetic, antioxidant, anti-infectious, and anti-inflammatory properties.Investigation of the geno-protective effect of curcumin on methotrexate induces chromosomal aberrations of spleen and bone marrow cells. In this study, 32 mice were used and divided into four groups (eight mice at each group) as follows: Group1 (negative control): Dimethyl sulfoxide was given intraperitoneally to mice every day for ten days.Group2 (positive control): Mice were received a single do

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Publication Date
Tue Jun 11 2019
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
The Protective Effect of Ethanolic Extract of Mentha spicata Against Irinotecan-Induced Mucositis in mice
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Irinotecan induced-mucositis is an inflammatory event of intestine caused by an increase in concentration of active metabolite 7­ethyl­10-hydroxycamptothecin (SN­38) in the intestine. Irinotecan must first be converted by a carboxylesterase (CES) to the active metabolite (SN­38), which is subsequently glucuronidated by the hepatic enzyme to SN38G. The SN-38G is deconjugated in the intestine to SN-38 via ?-glucuronidase produced by the intestinal bacterial flora, which accounts for SN-38 delayed intestinal mucositis of irinotecan. To study the protective effect of mentha in irinotecan-induced mucositis, intestinal mucositis induced by I.P injection of irinotecan (75mg/Kg/day) for 4 days. Mentha ethanolic extract orally administered to

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Publication Date
Tue Feb 16 2016
Journal Name
World Journal Of Pharmaceutical Research
ENDOCRINE REPRODUCTIVE EFFECTS OF PREGABALIN DRUG IN FEMALE ALBINO RATS
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The aim of present study was to investigate the effect of Pregabalin on hormonal profile of pituitary and ovarian hormones in female albino rats. Three groups of healthy adult female albino rats having fifteen rats in each group were selected for present study. The rats of groups G2 and G3 were administered with Pregabalin with two doses 150 mg and 300mg/kg b.wt/day respectively by orally route daily for 1month, 2 months, and 3 months. Animals of group G1 (Control) were given saline alone. After the experimental periods, the rats were sacrificed, and the study of hormonal profile was carried out by collecting blood samples from the heart puncture method, centrifuged sera and analyzing concentrations of estrogen, progesterone and gonadotropi

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Publication Date
Wed Mar 15 2023
Journal Name
Bionatura
Immune-protective effect of topical paquinimod administration against imiquimod-induced psoriasis-like inflammation in mice
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Psoriasis is a chronic, inflammatory condition that primarily affects the skin, hair, and joints and is associated with significant humanistic and economic consequences. This work induced psoriasis in mice using an imiquimod 5% cream, an immune response modifier that can cause psoriasis-like skin inflammation when given orally. Paquinimod is prepared as an ointment and has been topically given to mice before imiquimod application. In this study, albino mice were allocated into five groups and treated as follows: the control group received only a daily application of cream based on shaved back (62.5mg/2cm) with a daily topical dose of ointment for 14 consecutive days with the oral vehicle. The Imiquimod group received a daily topical

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Publication Date
Thu Apr 20 2023
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
A Protective effect of (Andrographis Paniculata) on 4-Vinylcyclohexene Diepoxide Induced ovarian Toxicity in Female Albino Rats: introduction
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Abstract

Background and objective: Protective effect of (Andrographis Paniculata) on 4-Vinylcyclohexene Diepoxide.

Material and methods:A group of 55 female albino rats undergo experiment on the outcome effect of 4-vinylcyclohexene Diepoxide injection for a priod of two weeks, as well as treatment effect of methanolic leaf extract of Andrographis paniculata oral administration for four weeks. Injection  concentrations (160 and 320mg/kg. B.W) also two different doses of treatment (100 and 200mg/kg. B.W) have been applied.

Results:The results on body weight and ovary weight were more evident when higher concentration dose was applied.

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