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.
In 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
... Show MoreThe study was carried out to determine the cytotoxic, antioxidant and gastro-protective effect of ethyl-4-[(3,5-di-tert-butyl-2-hydroxybenzylid ene)amino] benzoate (ETHAB) in rats.
Abstract Liver cancer with hepatocellular carcinoma a serious clinical illness that progresses quickly and has a bad prognosis because to increased malignancy. Fibrosis is the precursor of liver cancer, which progresses to cirrhosis and carcinoma Diethylnitrosamine (DEN) is a chemical molecule that has been used as a carcinogenic agent to promote cancer in test animals because of its strong carcinogenic potential. Herbal plants have long been used as inexpensive, effective alternatives to pharmaceuticals in various liver-associated complications, since they contain many bioactive compounds useful in liver disorders. Hibiscus tiliaceus L. (Malvaceae) contain various phytochemicals in the plant extracts such as Flavonoids, phe
... Show MoreBackground: The aim of this study was to evaluate the expression of fibroblast growth factor-2 and Heparanase in salivary pleomorphic adenoma, and to correlate the two studied markers with each other and with clinicopathological parameters including: age, sex, tumor site and histopathological presentation. Methods: Sections of twenty five formalin-fixed paraffin embedded tissue blocks specimens of salivary pleomorphic adenoma were immunostained using monoclonal antibodies (Fibroblast growth factor-2 and Heparanase) to assess their expression in this tumor. Results: The expression of fibroblast growth factor-2 and Heparanase were positive in all pleomorphic adenoma cases (100%). The positive expression of fibroblast growth factor-2 was signi
... Show MoreMethotrexate (MTX) is widely used chemotherapeutic agent with different side effects including germ cells toxicities. Silibinin is one of the structural isomers of silymarin, with different phytotherapeutic applications, and its possible protective effects against MTX induced germ cells damage were investigated in this work. Twenty five male mice were divided into five groups (n=5) allocated as follows: Group 1 received buffer for five days given by single intraperitoneal (IP) injection per day; Group 2 in addition to buffer for five days, animals received at day five single dose of 20mg/kg of MTX IP. Groups (3, 4, and 5) received respectively, (50, 100, or 150mg/kg body weight) of silibinin IP single daily dose for five days then at day fi
... Show MoreIntroduction and Aim: Diabetes mellitus patients almost always struggle with a metabolic condition known as chronic hyperglycemia. According to the World Health Organization, osteoporosis is a progressive systemic skeletal disorder that is characterized by decreasing bone mass and microstructural breakdown of bone tissue that increases susceptibility to fracture and increased risk of breaking a bone. Here, we aimed to compare the levels of CatK and total oxidative state in patients with diabetes and osteoporosis among the female Iraqi population and study the possible relationship between them. Materials and Methods: This study included 40 females with diabetes (Group G1), 40 with diabetes and osteoporosis (Group G2) and 40 norma
... 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
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