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.
Olive leaves extract is famous for its antioxidant and protective effects. In this study, the aqueous extract of Iraqi Olea europaea L. Leaves was investigated for its anti-diabetic effects against low double doses of alloxan induced Diabetes Mellitus in rats. Low double doses (75 mgKg body weight) of alloxan were injected intraperitoneally at day 1&29 of the experimental period in rats, whereas an aqueous extract of Iraqi Olea europaea L. Leaves was added continuously to their drinking water. Serum malondialdehyde concentration, total oxidative stress and oxidative stress index as oxidoreductive stress biomarker, activities of certain anti-oxidoreductive stress enzymes (glutathione peroxidase, super oxide dismutase and catalase) and concen
... Show MoreBackground Methotrexate (MTX) is a classical folic acid antagonist widely used in the treatment of malignant and non-malignant disorders. However, its clinical application is often restricted by concomitant adverse effects, including renal damage. Numerous studies have highlighted the role of oxidative stress and inflammation in mediating MTX-related nephrotoxicity. Therefore, the current study aimed to explore the possible renoprotective action of Citronellol (CT), a natural compound with prominent antioxidant and anti-inflammatory activities, against nephrotoxicity induced by MTX. Methods To fulfill our objective, 24 adult male Wistar rats were randomly allocated into four groups: control, MTX, 100 mg/kg CT plus MTX and 200 mg/kg C
... Show MoreBackground Methotrexate (MTX) is a classical folic acid antagonist widely used in the treatment of malignant and non-malignant disorders. However, its clinical application is often restricted by concomitant adverse effects, including renal damage. Numerous studies have highlighted the role of oxidative stress and inflammation in mediating MTX-related nephrotoxicity. Therefore, the current study aimed to explore the possible renoprotective action of Citronellol (CT), a natural compound with prominent antioxidant and anti-inflammatory activities, against nephrotoxicity induced by MTX. Methods To fulfill our objective, 24 adult male Wistar rats were randomly allocated into four groups: control, MTX, 100 mg/kg CT plus MTX and 200 mg/kg C
... Show MoreThe protective effect of ginger extract against cisplatin-induced hepatotoxicity and cardiotoxicity was evaluated in 30 albino white rats(weighing 200-300 gm ) classified into 5groups (6 rats per each group). The rats were treated with 0.5g/kg/day or 1g/kg/day ginger extract orally 5 successive days before and 5 successive days after induction of toxicity with intraperitoneal (IP) injection of (10mg/kg ) cisplatin, resulted in a significant reduction in the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) , total serum billirubin(TSB) , lactate dehydrogenase (LDH) and creatine kinase(CK) enzymes in comparison with the cisplatin treated animals; ginger extract
... Show Moreنظرة عامة: تُعرَّف المادة أو العامل الذي يمكن أن يؤثر على الحمض النووي أو الكروموسومات على أنه سم جيني. قد يؤدي تلف الحمض النووي في الخلية الجسدية إلى حدوث طفرة جسدية ، والتي قد تحفز التحول الخبيث ، في حين أن الضرر الذي يلحق بالخلية الجرثومية قد يؤدي إلى تغيير خاصية وراثية (طفرة في السلالة الجرثومية) (سرطان). أحد الأحماض الدهنية الأحادية غير المشبعة الأحادية غير الأساسية هو حمض البالميتوليك. بعد حمض الأوليك
... Show MoreMethotrexate (MTX) is a folate antagonist widely used in the treatment of neoplastic diseases; its biotransformation in the liver produced active metabolites that promote hepatotoxicity. The present study was designed to evaluate the hepatoprotective effect of aqueous extract of Camellia sinensis (Green tea) against MTX-induced liver damage in rats. A model of liver injury in rats was induced by intraperitoneal injection of 20mg/kg MTX as a single dose followed by saline and 1.25% and 2.5% aqueous extract of green tea (GTE) were orally administered 7 days prior and 5 days after MTX-intoxication as a sole source of drinking water. After killing the animals, blood samples were obtained for evaluation of serum levels of alanine and
... Show MoreThe aim of the present study was to investigate the nephroprotective, hypolipidemic and hypoglycemic effects of Allium porrum (leek) in rabbits with cisplatin nephrotoxicity. Forty adult male New Zealand rabbits were divided randomly into four groups (ten rabbits in each group) as follows: Group I: (negative control) (C) received oral daily dose of distilled water for 15 successive days. Groups II: (Leek) (L) received oral daily dose of aqueous leek extract (500mg/kg/day) for 15 successive days. Group III: (positive control) [cisplatin (CP)] received oral daily dose of distilled water for 15 successive days, and subsequently administered single dose of Cisplatin (3.5mg/kg/day) by intraperitoneal injection from day 10 for five da
... Show MoreThe objective of this study was to evaluate the impact two doses of Menaquinones-7 on hepatotoxicity induced by doxorubicin in rats. Sixty adult rats of both sexes were used in this study; the animals were randomly enrolled into six groups of 10 animals each. Group I: negative control (rats administered distilled water); Group II: Menaquinones-7 at a dose of 16 µg/kg; Group III: Menaquinones-7 at a dose of 48 µg/kg; Group IV: positive control (Doxorubicin 15 mg/kg); Group V: Menaquinones-7 at a dose of 16 µg/kg administered prior to a single dose of Doxorubicin 15 mg/kg; Group VI: Menaquinones-7 at a dose of 48 µg/kg administered prior to a single dose of Doxorubicin 15 mg/kg. On day twelve of the study, blood was
... Show MoreFatty acids, particularly omega-3, omega-6, and omega-9, play a vital role in various biological processes. As the body cannot synthesize omega-3 and omega-6, dietary sources of these fatty acids are essential. Each omega fatty acid has a distinct chemical structure, source, and function. Cisplatin (CP) treatment is known to cause acute kidney injury (AKI) due to its inflammatory effects. This study explored the renoprotective potential of omega-3-6-9 when co-ad-ministered with cisplatin in a mice model. We divided adult mice into five groups: a control group received 0.5 ml of liquid paraffin; a cisplatin-only group; two groups were treated with low (50 mg/kg) and high (100 mg/kg) doses of omega-3-6-9 plus cisplatin; and a final group rece
... Show Morehis study aimed to evaluate the effects of different doses of melatonin on liver function in adult rats. Eighteen Wistar adult albino rats (Rattus norvegicus), approximately 13–16 weeks old and weighing 230 ± 10 g, were randomly divided into three groups (n=6 per group) and treated orally for 30 days as follows: Group A1 received 10 mg/kg body weight (B.W) of melatonin; Group A2 received 20 mg/kg B.W of melatonin; and the control group (Group A) received distilled water. At the end of the treatment period, blood samples were collected via cardiac puncture, and serum was separated for biochemical analysis. Parameters assessed included oxidative stress markers (malondialdehyde (MDA), reduced glutathione (GSH)) and liver enzymes (aspa
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