Thymoquinone protects against cardiac damage from doxorubicin-induced heart failure in Sprague-Dawley rats

Pei, Zuowei; Hu, Jiahui; Bai, Qianru; Liu, Baiting; Cheng, Dong; Liu, Hainiang; Na, Rongmei; Yu, Qin

doi:10.1039/c8ra00975a

Cited by 13 publications

(9 citation statements)

References 27 publications

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“…In terms of tissue fibrosis, 5 studies that model the tissue fibrosis of different organs were included. For cardiac fibrosis, one study using doxorubicin-induced rats was included [38]. For lung fibrosis, 2 studies with bleomycin-induced rats [23] and paraquat-induced rats [42] were included.…”

Section: Resultsmentioning

confidence: 99%

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Effect of Nigella sativa and its bioactive compound on type 2 epithelial to mesenchymal transition: a systematic review

Nordin

Kamal

Yazid

et al. 2019

BMC Complement Altern Med

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BackgroundNigella sativa or commonly known as black seed or black cumin is one of the most ubiquitous complementary medicine. Epithelial to mesenchymal transition (EMT) of type 2 is defined by the balance between wound healing and tissue fibrosis, which is dependent to the state of inflammation. This systematic review is conducted to provide an overview regarding the reported effect of Nigella sativa and its bioactive compound on the type 2 EMT.MethodsA search was done in EBSCOHOST, OVID and SCOPUS database to obtain potentially relevant articles that were published between 1823 and August 2019. This review includes studies that focus on the effect of Nigella sativa and its bioactive compound on the events related to type 2 EMT.ResultsA total of 1393 research articles were found to be potentially related to the effect of Nigella sativa and its bioactive compound, thymoquinone on Type 2 EMT. After screening was done, 22 research articles met inclusion criteria and were included in this review. Majority of the studies, reported better wound healing rate or significant prevention of tissue inflammation and organ fibrosis following Nigella sativa or thymoquinone treatments. In terms of wound healing, studies included reported progression of EMT related pathological changes after treatment with Nigella sativa or thymoquinone. Alternatively, in terms of fibrosis and inflammation, studies included reported reversal of pathological changes related to EMT after treatment with Nigella sativa or thymoquinone.ConclusionThrough this review, Nigella sativa and thymoquinone have been associated with events in Type 2 EMT. They have been shown to promote wound healing, attenuate tissue inflammation, and prevent organ fibrosis via regulation of the EMT process.

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Section: Resultsmentioning

confidence: 99%

“…Treatment of thymoquinone has been shown to have anti-fibrotic and anti-apoptosis effect in this study. The study revealed the potential of thymoquinone as cardioprotective agent for myocardial fibrosis [38].…”

Section: Resultsmentioning

confidence: 99%

Effect of Nigella sativa and its bioactive compound on type 2 epithelial to mesenchymal transition: a systematic review

Nordin

Kamal

Yazid

et al. 2019

BMC Complement Altern Med

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“…Rats treated with TQ before ISO administration exhibited less brous tissue deposition in the myocardium as indicated by the histopathological examination of cardiac sections, compared to the vehicle-pretreated ISO group. The mechanism of this effect may be related to the TQinduced downregulation of the expression of the protein levels of transforming growth factor beta, collagen I, collagen III and α-smooth actin that play a crucial role in the pathogenesis of myocardial brosis (Bujak and Frangogiannis 2007;Pei et al 2018).…”

Section: Discussionmentioning

confidence: 99%

“…It is the main active ingredient derived from Nigella sativa seeds, commonly used as a food supplement and in folk medicine (Ahmad et al 2013). Thymoquinone reduces the generation of reactive oxygen species (ROS) and suppresses oxidative stressinduced oxidative damage in several tissues as in cyclosporine A-induced nephrotoxicity (Farag et al 2015), acetaminophen-induced hepatotoxicity (Awad et al 2016) and doxorubicin-induced cardiotoxicity (Pei et al 2018). Thymoquinone is regarded by many investigators as a potent antioxidant with additional anti-in ammatory properties that may expand its therapeutic potential especially in cardiovascular diseases (Shabana et al 2013).…”

Section: Introductionmentioning

confidence: 99%

Thymoquinone dose-dependently attenuates myocardial injury induced by isoproterenol in rats via integrated modulation of oxidative stress, inflammation, apoptosis, autophagy and fibrosis

Farag

Khalifa

El-Hadidy

et al. 2021

Preprint

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As rats develop myocardial infarction (MI) like lesions when injected with large doses of isoproterenol (ISO), this investigation was designed to evaluate the effects of low and high doses of thymoquinone (TQ) on ISO-induced myocardial injury in rats. Adult male rats were divided into control, TQ20 (20 mg/kg/day), TQ50 (50 mg/kg/day), and ISO, TQ20 + ISO and TQ50 + ISO groups. In these rats, biochemical, immunobiochemical and histopathological studies were carried out to evaluate myocardial oxidative stress, inflammation, apoptosis, fibrosis and autophagy and serum cardiac biomarkers. The results showed that TQ pretreatment in ISO-administered rats produced a dose-dependent significant reduction of the myocardial infarct size, markedly reduced the ISO-induced elevation in serum cardiac markers and demonstrated several other important findings related to the cardioprotective efficacy of TQ. First, this study is the first reported research work showing that TQ treatment could increase the myocardial reduced glutathione baseline level, adding an indirect antioxidant effect to its known direct free radical scavenging effect. Second, pretreatment with TQ significantly reduced the markers of myocardial oxidative stress, inflammation, fibrosis and apoptosis. Third, TQ acted as an autophagy enhancer ameliorating myocardial cell damage and dysfunction. Thus, the changes associated with ISO-induced myocardial injury were ameliorated with TQ pretreatment. Additionally, the extent of observed improvement was significantly greater with the high TQ dose than with the low dose use. These findings raise the possibility that TQ may serve as a promising prophylactic cardioprotective therapy for patients who are at risk of developing myocardial injury as in cases of MI.

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“…Doxorubicin hydrochloride (Dox), a chemotherapeutic drug, which intercalates with DNA, is used for a wide range of cancer treatments [ 4 , 5 ], however it is associated with severe side effects, e.g., cardiac damage, vomiting, bone marrow suppression, tissue damage at the site of injection, and myelosuppression, which prevent it from being the prominent first choice [ 6 , 7 ]. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a protein considered as a promising candidate for treatment owing to its selective apoptotic effect on cancer cells [ 8 , 9 ], is not therapeutically effective, as IV administration leads to insufficient amount at the target site due to rapid degradation in vivo.…”

Section: Introductionmentioning

confidence: 99%

Engineering of Doxorubicin-Encapsulating and TRAIL-Conjugated Poly(RGD) Proteinoid Nanocapsules for Drug Delivery Applications

et al. 2020

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Proteinoids are non-toxic biodegradable polymers prepared by thermal step-growth polymerization of amino acids. Here, P(RGD) proteinoids and proteinoid nanocapsules (NCs) based on D-arginine, glycine, and L-aspartic acid were synthesized and characterized for targeted tumor therapy. Doxorubicin (Dox), a chemotherapeutic drug used for treatment of a wide range of cancers, known for its adverse side effects, was encapsulated during self-assembly to form Dox/P(RGD) NCs. In addition, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which can initiate apoptosis in most tumor cells but undergoes fast enzyme degradation, was stabilized by covalent conjugation to hollow P(RGD) NCs. The effect of polyethylene glycol (PEG) conjugation was also studied. Cytotoxicity tests on CAOV-3 ovarian cancer cells demonstrated that Dox/P(RGD) and TRAIL-P(RGD) NCs were as effective as free Dox and TRAIL with cell viability of 2% and 10%, respectively, while PEGylated NCs were less effective. Drug-bearing P(RGD) NCs offer controlled release with reduced side effects for improved therapy.

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Thymoquinone protects against cardiac damage from doxorubicin-induced heart failure in Sprague-Dawley rats

Abstract: Heart failure is a complex end stage result of various cardiovascular diseases, and has a poor prognosis.

Cited by 13 publications

References 27 publications

Effect of Nigella sativa and its bioactive compound on type 2 epithelial to mesenchymal transition: a systematic review

Effect of Nigella sativa and its bioactive compound on type 2 epithelial to mesenchymal transition: a systematic review

Thymoquinone dose-dependently attenuates myocardial injury induced by isoproterenol in rats via integrated modulation of oxidative stress, inflammation, apoptosis, autophagy and fibrosis

Engineering of Doxorubicin-Encapsulating and TRAIL-Conjugated Poly(RGD) Proteinoid Nanocapsules for Drug Delivery Applications

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