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Protective effect of cafestol against doxorubicin-induced cardiotoxicity in rats by activating the Nrf2 pathway

Doxorubicin (DOX) is an efficient antineoplastic agent with a broad antitumor spectrum; however, doxorubicin-associated cardiotoxic adverse effect through oxidative damage and apoptosis limits its clinical application. Cafestol (Caf) is a naturally occurring diterpene in unfiltered coffee with unique antioxidant, antimutagenic, and anti-inflammatory activities by activating the Nrf2 pathway. The present study aimed to investigate the potential chemoprotective effect of cafestol on DOX-induced cardiotoxicity in rats. Wistar albino rats of both sexes were administered cafestol (5 mg/kg/day) for 14 consecutive days by oral gavage alone or with doxorubicin which was injected as a single dose (15 mg/kg intraperitoneally at day 14) to induce toxicity. The result showed that Caf significantly improved cardiac injury induced by doxorubicin, decreased serum levels of CK-MB, LDH, ALP, and ALT, and improved histopathological changes. In addition, cafestol significantly inhibited DOX-induced cardiac oxidative stress as seen in the reduced level of MDA and increased GSH, SOD, CAT, and Gpx-1 cardiac tissue levels; cafestol significantly enhanced Nrf2 gene and protein expression and promoted the expression of downstream antioxidant genes HO-1 and NQO-1 and downregulated Keap1 and NF-κB genes’ expression; in addition, Caf significantly reduced inflammatory mediators, TNF-α, and IL-1β levels and inhibited cardiac apoptosis by modulating Bax and Casp 3 tissue levels and reduced TUNEL-positive cardiomyocytes. In conclusion, the present study confirmed that cafestol improved the cardiotoxic effects induced by doxorubicin through the regulation of apoptosis and oxidative stress response through the Nrf2 pathway; this study suggests that cafestol may serve as a potential adjuvant in chemotherapy to alleviate DOX-induced toxicities.

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Publication Date
Fri Dec 29 2023
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Protective Effect of Omega-7 against Doxorubicin-Induced Cardiotoxicity in Male Rats

Background: Doxorubicin is considered one of the most effective anticancer drugs, yet it is use is limited by its side effect mediated by the generation of reactive oxygen species. Omega-7, an antioxidant has shown to have a cardioprotective effect.

Aim of the study: evaluate a possible protective effect of omega-7 against doxorubicin-induced cardiotoxicity in male rats.

Methods: twenty-eight male rats were divided into 4 groups (7 for each group).  Group 1 (Negative control): healthy animals received normal saline orally as the vehicle for eight successive days and were sacrificed on day 9. Group 2 (positive control): animals that r

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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
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 Mar 31 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Protective Effect of Benfotiamine against Doxorubicin-Induced Cardiotoxicity in Rabbits

The protective effect of benfotiamine against doxorubicin-induced cardiotoxicity was evaluated in rabbits. Pretreatment of rabbits with 70mg/kg benfotiamine orally 7 days before induction of cardiotoxicity with I.V 15mg/kg doxorubicin. injection resulted in significant reduction of the activities of lactate dehydrogenase and creatine phosphokinase enzyme in the serum compared to doxorubicin treated animals; benfotiamine also improves the histological changes produced by doxorubicin in the cardiac muscle compared to control. In conclusion, benfotiamine when used concomitantly with doxorubicin protects the myocardium against the cardiotoxicity induced by this cytotoxic drug.

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Publication Date
Tue Mar 28 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Protective Effect of Ginger Extract Against Cisplatin-Induced Hepatotoxicity and Cardiotoxicity in Rats.

The 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

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Publication Date
Wed Mar 29 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
The Protective Effect of Honey Against Amikacin- induced Nephrotoxicity in Rats

Drug –induced nephrotoxicity is an important cause of renal failure. Aminoglycoside antibiotics, such as amikacin, which causes ototoxicity and nephrtotoxicity as a main side effects, this is focused on the use of natural materials as antioxidants against the toxic oxidative action that exert a cell damaging effect. The most important one of these materials is the honey. The aim of this work is to evaluate the antioxidant effects of honey against amikacin – induced nephrotoxicity.18 albino rats divided into 3 groups (6 rats per each group), group 1 received I.P daily dose of normal saline (control), group 2 received (35  mg/kg/day) I.P dose of amikacin ,and group 3 received (35mg/kg/day) of amikacin I.P dose in combina

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Publication Date
Sat Jun 19 2021
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Protective Effects of Safranal Against Selenite-Induced Cataract in Rats

         Cataract, which is the opacity inside clear ocular lens of eye, result in the scattering of visible light as it passes via the lens and consequently deterioration in optical image. The aim of the present study was to investigate whether safranal, an active constituent of Crocus sativus L. stigmas, has a protective effect on the cataract in the rat's pups. The animals were randomly divided into five groups, each of which consisted of 7 rat pups. Group I served as normal control (vehicle administration). For testing cataract induction, animals of Groups II, III, and IV were administered a single subcutaneous injection of sodium selenite on postpartum day 12. After sodium selenite intoxicatio

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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)
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Publication Date
Thu Mar 30 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Study of the Protective Effects of Benfotiamine Against CCl4-Induced Hepatotoxicity in Rats

Liver is considered as the first target for the toxic effects of toxins and other xenobiotics, and this can be attributed to its role as a site which receive all absorbed xenobiotics from the gastrointestinal tract and its role as a major site for biotransformation of xenobiotics. The present study was designed to evaluate the possible hepatoprotective effect of benfotiamine against CCl4-induced hepatotoxicity in rats. The study was conducted on 48 male albino rats; the animals were allocated into 8 groups (6 rats in each group) and treated as follow: 4 groups treated with oral doses of either normal saline, benfotiamine (100 mg/kg), thiamine (100 mg/kg), N-acetylcystein (400 mg/kg) only without induction of hepatic damage. Th

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Publication Date
Fri Jun 16 2023
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Study The Lung-Protective Effects of Riboflavin and Cyanocobalamin Against Lung Toxicity-Induced by Cyclophosphamide in Rats

Cyclophosphamide (CP) is a cytotoxic alkylating agent it's used associated with different side effects including lung toxicity. Vitamin B2 and vitamin B12 have lung-protective effects. This study was designed to evaluate lung-protective effects of both vitamins against lung toxicity induced by cyclophosphamide. seventy healthy adult albino male and female rats divided into seven groups each group containing ten rats were used in the present study and treated for seven days. On day eight rats were sacrificed and serum was obtained for glutathione and total antioxidant capacity measurement and lung extracted for immunohistochemical study; both vitamins significantly (P<0.05) increased glutathione and total antioxidant capacity in compar

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Publication Date
Mon Dec 23 2019
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Inhibition of NF-kB Pathway by Gggulsterone in the Protective Effects of Cyclophosphamide-Induced Renal Toxicity

Cyclophosphamide which acts as cytotoxic alkylating agent can induce a renal damage through the toxic metabolites which result from metabolic activation of Cyclophosphamide by cytochrome P-450 inside hepatocyte and develop renal toxicity by direct binding with cellular organelles in the urinary tract cells. Guggulsterone is a sterol derived from plant has ability to bind to farsenoid X receptor, mineral corticosteroid receptor, androgen receptor, glucocorticoid receptor and estrogen receptor.

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