Background 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 CT plus MTX. At the end of the study, the experimental rats were anesthetized, blood samples were collected for biochemical assays, and the kidneys were surgically removed for biochemical and gene expression analyses, after which all rats were sacrificed by exsanguination. Results Compared to the MTX-treated group, our results revealed that pre-supplementation with 100 or 200 mg/kg CT remarkably ameliorated renal damage biomarkers, including serum urea, serum creatinine, and kidney injury molecule-1 (KIM-1). In addition, pre-treatment with 100 or 200 mg/kg CT enhanced the activity of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx), diminished renal malondialdehyde (MDA) contents, and attenuated inflammation by suppressing renal nuclear factor kappa B (NF-κB) signaling and diminishing tumor necrosis factor-alpha (TNF-α) gene expression. Moreover, pre-treatment with 200 mg/kg CT markedly reduced interleukin-1 beta (IL-1β) gene expression. Conclusion Our findings demonstrate, for the first time, that CT can serve as a new promising agent for mitigating nephrotoxicity induced by MTX through its antioxidant and anti-inflammatory properties.
Survivin, a member of inhibitor of apoptosis family is increasingly used as a target for cancer therapy design because it has a key role in cell growth and inhibition of cell apoptosis. Also it can be used as a biomarker for targeting cancer because it is found in almost all cancer but not normal cells. Our strategy was to design (computationally) a molecule to be used as survivin inhibitor. This molecule was named lead10 and was used furthermore to find (virtually) existing drugs with a good survivin inhibition activity.
Abstract
Mitoxantrone is an antitumor agent used in the treatment of breast and prostate cancer, acute leukemia, lymphoma, and also in the treatment of multiple sclerosis due to its immunosuppressive properties. The mitoxantrone's cardiotoxicity is irreversible, dose-dependent, and it may occur years after treatment. Zinc is considered as an essential mineral for cell division and the synthesis of DNA and protein; furthermore, such mineral has an important role in states of cardiovascular diseases; and may have protective effects in coronary artery disease and cardiomyopathy.
Objective: The current study is designed to investigate effects of two different doses of zinc sulfat
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The aim of the current study was to investigate the possible protective effect of graded doses (5, 10, and 15mg/kg) of pyridoxine hydrochloride intraperitoneally injected against (15mg/kg) doxorubicin-induced cardiotoxicity in female rats. Fifty-six (56) Wistar albino female rats were utilized weighing 180-200 gm allocated into eight groups, seven rats each; Group I: negative control distilled water; Group II: Pyridoxine (5mg/kg); Group III: Pyridoxine (10mg/kg); Group IV: Pyridoxine (15mg/kg); Group V: doxorubicin (15 mg/kg); Group VI: Pyridoxine (5 mg/kg) prior to
... Show MoreIn the present study, five derivatives have been designed to be synthesized as possible mutual prodrugs for 5-Fluorouracil (5-FU) and non steroidal anti-inflammatory drugs (NSAIDs) to selectively deliver the drugs into the cancer cells. The synthesis of the target compounds were accomplished following multistep reaction procedures, the chemical reaction followed up and the purity of the products were checked by TLC. The structure of the final compounds and their intermediates were confirmed by their melting points, infrared spectroscopy and elemental microanalysis, the hydrolysis of compound III was studied using HPLC technique. According to the results mentioned above, compounds (I−V) can be good candidates as possible mutual prod
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At any moment, the continuous usage of medications can accompanied by DNA damage and the accumulation of such damages can cause serious consequences. Antidepressants are long-term used drugs and the incidence of their genotoxic impacts cannot be excluded. Therefore, this work was designed to investigate the possible genotoxic effects of the commonly used antidepressants (fluoxetine and amitriptyline) in adult male rats.
Detection of DNA damage in individual cells was assessed by comet and micronucleus assays in three different cell populations i.e. liver, testis and bone marrow tissues of 24 swiss albino adult male rats. The animals were randomly allocated into three groups of 8 rats ea
... Show MoreRheumatoid arthritis is an autoimmune diseasecharacterized by chronic inflammationthat affects joints and cartilage. Bone complications such asRA-relatedosteoporosis are one of the most extra-articular manifestations. Many inflammatory mediators are released during RA disease pathophysiology; these mediators stimulate osteoclast genesis of bone by direct effects on RANKL and OPG. The study aimedto measure RANKL, OPG in RA patients treated with Etanercept only and other groups treated with Methotrexate onlyat baseline and after three months to evaluate bone state. An observational case-control prospective study was done on 30 RA patients who received MTX, 30 RA patients who received ETN, and 30 healthy,age-matched control groups. The
... Show MoreThe impacts of the inflammatory process on neoplasia development were observed in many cancer, it has a great role in the etiology, development and progression of invasive colorectal tumors. This study was designed to investigate the BRAF mutation and assist the clinicopathological parameter in some Iraqi bowel inflammation and colorectal cancer patients. Thirty patients were enrolled in this study (15 suffering bowel inflammation and 15 having colorectal cancer). BRAF gene was screened for the presence of mutations using PCR technique and direct sequencing. .The results revealed no BRAF mutation in position 1799 for exon fifteen in both samples of bowel inflammation and colorectal cancer. These results were confirmed previous arti
... Show MoreThe design of components subjected to contact stress as local compressive stress is important in engineering application especially in ball and socket Joining. Two kinds of contact stress are introduced in the ball and socket joint, the first is from normal contact while the other is from sliding contact. Although joining two long links (drive shaft in steering cars) will cause the effect of flexural and tensional buckling stress in hollow columns through the ball and socket ends on the failure condition of the joining mechanism. In this paper the consideration of the combined effect of buckling Load and contact stress on the ball and socket joints have been taken, epically on the stress distribution in the contact area. Different
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