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Unleashing the cardioprotective potential of Ezetimibe against Doxorubicin-induced cardiotoxicity in Wistar rats: Targeting oxidative stress and NF-κB-mediated inflammation
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Background Doxorubicin (DOX) is a potent antineoplastic agent used in treating various adult and pediatric cancers, but it tends to provoke dose-dependent cardiotoxicity. Ezetimibe (EZE), a cholesterol-lowering drug, has been reported to possess defensive actions against oxidative stress and inflammation, which are two of the main proposed mechanisms underlying the development of DOX-induced cardiotoxicity (DIC), hence, we aimed to inspect the possible protective effect of EZE against DIC in rats. Methods 24 adult male Wistar rats were allocated into four groups of six: control, DOX, 10 mg/kg EZE plus DOX and 20 mg/kg EZE plus DOX. At the end of the study, the experimental rats were anesthetized and blood samples were collected for biochemical analysis, after which the hearts were excised and heart tissue samples were obtained for biochemical and gene expression analyses. Results Pretreatment with EZE at a dose of 10 or 20 mg/kg alleviated cardiac damage induced by DOX, as EZE blunted the rise in serum levels of cardiac injury biomarkers, including cardiac troponin I (cTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Additionally, pretreating rats with EZE at either dose mitigated DOX-induced oxidative stress by elevating the levels of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx), with consequent reduction in the lipid peroxidation biomarker malondialdehyde (MDA) in cardiac tissues. Furthermore, pretreatment with either dose of EZE hindered DOX-mediated inflammation, where EZE suppressed cardiac nuclear factor-kappa B (NF-κB) signaling and negatively regulated the gene expression of its downstream proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) with either dose and interleukin-1 beta (IL-1β) with the higher one. Conclusions Our findings indicate that EZE exhibited cardioprotection against DIC in rats, which makes EZE an interesting area for further investigations, animal- and human-wise, that can pave the way for a potential clinical application in preventing DIC in the future.

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Publication Date
Fri Nov 01 2024
Journal Name
Human Antibodies
Free radicals and oxidative stress: Mechanisms and therapeutic targets
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BACKGROUND:

Free radicals are small extremely reactive species that have unpaired electrons. Free radicals include subgroups of reactive species, which are all a product of regular cellular metabolism. Oxidative stress happens when the free radicals production exceeds the capacity of the antioxidant system in the body’s cells.

OBJECTIVE:

The current review clarifies the prospective role of antioxidants in the inhibition and healing of diseases.

METHODS:

Information on oxidative stress, free radicals, reactive oxidant species, and natural and synthetic antioxidants was obta

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Publication Date
Sat Aug 01 2020
Journal Name
Research Journal Of Pharmacy And Technology
Evaluation of in vivo and in vitro protective effects of quercetin on lipopolysaccharide-induced inflammation and cytotoxicology
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Quercetin, one of the flavonoids family member, can be found in many vegetables, fruits, and beverages with a noticeable nutritional pharmacological properties. This study was aimed to evaluate the ability of quercetin to inhibit lipopolysaccharide (LPS) that induced lethal toxicity in vivo, and to elucidate the importance of the quercetin as an antitumor agent in breast cancer cell line MCF-7.In vivo experiments included the effect of hesperidin and LPS on the liver and spleen of male mice. In the liver, the antioxidant activity was measured by estimating the concentration of glutathione (GSH), and catalase (CAT), while in the spleen, the concentration of cytokines was measured including IL-33 and TNF-α. In vitro experiments included MTT

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Publication Date
Wed May 31 2017
Journal Name
Iraqi Journal Of Market Research And Consumer Protection
THE EFFECT OF ALCOHOLIC EXTRACT OF ANETHUM GRAVEOLENS IN ALLOXAN INDUCED DIABETIC RATS.: THE EFFECT OF ALCOHOLIC EXTRACT OF ANETHUM GRAVEOLENS IN ALLOXAN INDUCED DIABETIC RATS.
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Active compounds were extracted from Anethum gravoelens to produce safety vegetable treat for diabetic, the results showed that alcoholic extract of Anethum gravoelens contain Alkaloid, glycosides, phenols, resins, saponins, coumarins, flavonoide, terpenes, steroids and volatile oils. after that it was studied the effect of alcoholic extract at dose 50, 100 mg/kg of body weight in reduced glucose level in serum of diabetic rats induced by alloxan, after the end of experiment for period 30 days the rats fasting 12 hours to measure the level of glucose in serum, the result showed asignificant decrease in serum glucose level of rats treated with extract in comparison with positive group (alloxan), So biochemical tests showed significant dec

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Publication Date
Sun Mar 15 2020
Journal Name
Journal Of Baghdad College Of Dentistry
Oxidative stress status in hypertensive patients on amlodipine treatment
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Background: Oxidative stress may contribute to the etiology of hypertension in humans. Oxidative stress is an imbalance between reactive oxygen species (ROS) and antioxidant defense mechanisms, causing damage to biological macromolecules and dysregulation of normal metabolism and physiology. Amlodipine as an antihypertensive agent is a long-acting calcium channel blocker that dilates blood vessels and improves blood flow. The aim of this study was to assess the oxidative stress in hypertensive patients on Amlodipine treatment through the assessment of salivary Malondialdehyde (MDA) and superoxide dismutase (SOD) as a marker of oxidative stress.

Mat

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Publication Date
Thu Dec 09 2021
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Thymoquinone Attenuates Immune Mediated Liver Injury Induced by Concanavalin A in Mice
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Autoimmune hepatitis is an inflammatory disease and its incidence has been increasing. The features of hepatitis are the release of inflammatory cytokines, the elevation of AST and ALT, and hepatocyte apoptosis and necrosis. Concanavalin A considered as essential model represents the acute immune-mediated liver damage in rodents. Thymoquinone is well known herbal compound that exert hepatoprotective, anti-inflammatory, and antioxidant activity. In this study, we focus on the immunoregulatory and liver protective effect of thymoquinone in a mouse model of concanavalin A-induced liver injury.

Twenty-four male mice were randomly divided into four groups each containing six animals: Negative control group, concanavalin A model group,

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Publication Date
Sun Sep 15 2024
Journal Name
Iraqi Journal Of Pharmaceutical Sciences( P-issn 1683 - 3597 E-issn 2521 - 3512)
Biomarkers of Oxidative Stress in Diabetic Microvascular Complications Review Article
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Reactive oxygen species (ROS) are produced as a result of biochemical processes that are not in balance with the body's antioxidant defense mechanism. This metabolic dysfunction is referred to the oxidative stress (OS).  Metabolic dysfunction-associated diseases are affected by changes in the redox balance. It is now widely recognized that oxidative stress significantly affects diabetes mellitus (DM), particularly type 2 diabetes. The biochemical changes associated with  DM could  disturb the oxidative milieu, leading to several microvascular complications in diabetic patients. Thus, DM is a perfect disease to explore the harmful consequences of oxidative stress and how to treat it. Oxidative stress triggered by hyperglycemia is

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Publication Date
Wed Jun 30 2010
Journal Name
Al-kindy College Medical Journal
The Influences of Aminophylline and Indomethacin in Glycerol-Induced Acute Renal Failure in Rats
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Background: Adenosine mediates homodynamic
changes and resulted in the production of acute renal
failure (ARF) in female Albino-Wister rats, therefore,
adenosine level increases highly in ARF.
Objective: This experiment was designed to
investigate the effect of the adenosine antagonist
aminophylline and the adenosine agonist indomethacin on glycerol-induced ARF.
Method: Glycerol induced ARF was produced by a
single dose (10ml/kg, 50%v/v with distilled water i.m)
in rats, which were restricted to drinking water.
Aminophylline was used in our study in a dose of
25mg/kg, i.p) while the dose of indomethacin was
10mg/kg, i.p), assessment of renal function was done
by measuring blood urea
nitrogen (BUN

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Publication Date
Mon Jan 01 2024
Journal Name
Aip Conference Proceedings
The role of advanced glycation end products and oxidative stress in the pathophysiology of thyroid disorders
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Publication Date
Fri Feb 01 2019
Journal Name
Journal Of Pharmaceutical Sciences And Research
Protective Effects of Quercetin on Lipopolysaccharide -Induced Inflammation and Lipid Peroxidation in BALB/c Male Mice
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In the resent years, there is a robust scientific interest in discovery of new anti-septic and anti-oxidant naturally products with no/or limited side effects. The current study aimed to investigate the protective role of the quercetin on inflammations induced by lipopolysaccharide (LPS) in male mice A number of criteria included i.e. liver and spleen index and IL-6 and IL1-β cytokines level in spleen homogenate were considered. Sixty male mice (8-9 week age) was divided into six groups and treated for 5 days as the following: the first group represented control, the second and third group were injected with 5, 10 mg/kg b.w doses of quercetin respectively. While the fourth and fifth groups were co-treatment with (5, 10 mg/kg b.w.) intraper

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Publication Date
Tue May 06 2014
Journal Name
Plos One
Gastroprotective Activity of Ethyl-4-[(3,5-di-tert-butyl-2-hydroxybenzylidene) Amino]benzoate against Ethanol-Induced Gastric Mucosal Ulcer in Rats
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The 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.

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