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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
Thu Dec 06 2018
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Effects of Vitamin E and Q10 Supplementation against Doxorubicin-Induced Neurotoxicity in Rats
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Publication Date
Thu Dec 06 2018
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn: 1683 - 3597 , E-issn : 2521 - 3512)
Effects of Vitamin E and Q10 Supplementation against Doxorubicin-Induced Neurotoxicity in Rats
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Doxorubicin (DOX) is a chemotherapeutic agent; it is widely used in human malignancies. Its long-term use can cause neurobiological side-effects. Vitamin E and Coenzyme Q10may possess neuroprotective effects. This work was designed to investigate the effect of vitamin E and the coenzyme Q10(CoQ10) supplementation on neurotoxicity induced by doxorubicin(DOX) in rats. Forty nine adult rats of both sexes were used in this study; the animals were randomly enrolled into seven groups of 7 rats each. Group I: negative control (rats administered corn oil); Group II: Vitamin E at a dose of 100mg/kg/d for 3 weeks ; Group III: CoQ10 at a dose of 50 mg/kg/d for 3 weeks; Group IV: positive control (Doxorubicin 2

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Publication Date
Mon Aug 22 2022
Journal Name
Biochemical And Cellular Archives
Measurement of inflammation and oxidative stress biomarkers induced by cigarette smoke among Iraqi smokers.
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To determine the association between cigarette smoking and oxidative stress, a study was conducted in the period from January 2020 to April 2021, at College of Medicine, Al-Nahrain University, Baghdad, Iraq. The Enzyme-linked immunosorbent assay (ELISA) technique was utilized for measurement the antioxidant enzymes including: Glutathione superoxide (GPX) and catalase (CAT) and the biomarker of lipid peroxidation Malondialdehyde (MDA). Also, the gene expression of Nrf2 and HO-1were determined by using RT-PCR technique. The results indicate lower level of both GPX and CAT (p ≤ 0.001) in smokers compared with non-smokers. While the result of MDA indicate higher level in smokers (p≤0.001) compared with nonsmokers. The Nrf2 and HO-1 gene exp

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Publication Date
Wed Nov 01 2023
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Protective Effects of Citronellol Against Rhabdomyolysis-Induced Acute Kidney Injury in Mice by Inhibiting NF-κB and IL-1β
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Objectives: acute kidney injury (AKI) is a serious pathophysiology side effect of rhabdomyolysis. Inflammatory mechanisms play a role in the development of rhabdomyolysis-induced AKI. Citronellol (CT) is a naturally occurring monoterpene alcohol (3,7-Dimethyl-6-often-1-ol) found in aromatic plant species' essential oils. In this study, we explored the protective effects of Citronellol on glycerol-induced AKI.

Methods: Four groups of eight mice each (n=8) were formed by randomly dividing the animals into the groups, glycerol-induced AKI model group, low-dose CT-treated group (50mg/kg), high-dose CT-treated group (100mg/kg), and control group. The renal functions of mice from all groups were evalua

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Publication Date
Fri Jun 07 2024
Journal Name
Asian Pacific Journal Of Cancer Prevention
The Effect of NF-κB Deactivation on Cancer Cell Response to ALA Mediated Photodynamic Therapy
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due to the presence of chemoresistance and the risk of tumor recurrence and metastasis. There is a pressing necessity to develop efficient treatments to improve response for treatment and increase prolong survival of breast cancer patients. Photodynamic therapy (PDT) has attracted interest for its features as a noninvasive and relatively selective cancer treatment. This method relies on light-activated photosensitizers that, upon absorbing light, generate reactive oxygen species (ROS) with powerful cell-killing outcomes. Nuclear factor kappa B (NF-κB), a transcription factor, plays a key role in cancer development by regulating cell proliferation, differentiation, and survival. Inhibiting NF-κB can sensitize tumor cells to chemotherapeuti

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Publication Date
Mon Dec 25 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn: 1683 - 3597 , E-issn : 2521 - 3512)
Impacts of Graded Doses of Pyridoxine on the Biomarkers, Aspartate Aminotransferase, lactate Dehydrogenase and Total Antioxidant Capacity in Doxorubicin-Induced Cardiotoxicity in Female Rats
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Abstract:        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 doxorubicin (15 mg/kg); Group VII: Pyridoxine (10 mg/kg) prior to doxorubicin (15 mg/kg); Group VIII: Pyridoxine (15 mg/kg) prior to doxorub

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Publication Date
Mon Dec 25 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
The Impacts of Graded Doses of Pyridoxine on the Biomarkers, Aspartate Aminotransferase, lactate Dehydrogenase and Total Antioxidant Capacity in Doxorubicin-Induced Cardiotoxicity in Female Rats
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Abstract:

       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

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Publication Date
Sat Jul 05 2025
Journal Name
Journal Of Research In Pharmacy
Evaluation the antioxidant effect of chromium picolinate in doxorubicin induced cardiotoxicity in a rat model
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Doxorubicin (DOX) is a potent antineoplastic drug used to treat many types of human tumor. The long-term adverse effect is cardiomyopathy. Chromium is an essential trace element mostly used to regulate glucose levels and enhance the response to insulin, especially in diabetes. Current study aimed to evaluate the cardioprotective effect of chromium picolinate against doxorubicin-induced cardiotoxicity in 28 male rats divided into four groups. Group I (Control group): received distilled water orally for 8 days. Group II (Doxorubicin group): received distilled water orally for 7 days, followed by a single doxorubicin dose (25 mg/kg) intraperitoneally. Group III (Chromium 2 mg): received chromium picolinate at a dose

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Publication Date
Wed Nov 01 2023
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Protective Effect of Cafestol on Doxorubicin-induced Genotoxicity in Rats
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Doxorubicin is an efficient antineoplastic agent that has a broad antitumour spectrum; however, its genotoxic adverse effects on normal cells can be produced through oxidative damage, and this limits its clinical application. Cafestol is a naturally-occurring diterpene in unfiltered coffee with noteworthy antioxidant, antimutagenic and anti-inflammatory activities.

The present study aimed to investigate the possible protective effect of cafestol against doxorubicin-induced chromosomal and DNA damage in rat bone marrow cells. Wistar

Albino rats of both sexes were administered cafestol (5mg/kg body weight once

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Publication Date
Fri Sep 29 2023
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Protective Effect of Cranberry Extract against Cisplatin-Induced Nephrotoxicity by Improving Oxidative Stress in Mice
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   Cranberry (Vaccinium macrocarpon) is a North American natural fruit. consumed as food and used for health promotion and prevention of various diseases. Aim. The present study was designed to evaluate the protective effect of cranberry fruit extract on nephrotoxicity induced by cisplatin in mice by measuring selected oxidative stress markers. Methods. Twenty-eight male albino mice were used in this study. The animals were divided into 4 groups as follows: Group I [Negative Control]/orally-administered normal saline for 7 successive days; Group II [Orally-administered cranberry fruit extract alone (200 mg/kg) for 7 successive days; Group III/Mice IP injection with cisplatin (12mg/kg) on day 7 and; Group IV [Orally-administered cr

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