Protective Effect of Thymoquinone Against Doxorubicin–induced Cardiotoxicity in Rats: A Possible Mechanism of Protection

Nagi, Mahmoud N.; Mansour, Mahmoud A.

doi:10.1006/phrs.1999.0585

Cited by 266 publications

(207 citation statements)

References 17 publications

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“…TQ has also been reported to enhance antitumor activity of ifosfamide in Ehrlich ascites carcinoma -bearing mice (8), prevent cisplatin-induced nephrotoxicity in mice and rats (19), ameliorate benzo(a)pyrene-induced forestomach carcinogenesis (20), inhibit cyclooxygenase 2 (COX-2) expression and prostaglandin production in a mouse model of allergic airway inflammation (21), and protect against doxorubicin-induced cardiotoxicity in mice (22). How TQ manifests these activities is not fully understood, but it has been shown to down-regulate the expression of Bcl-x L (11), COX-2 (21), iNOS (23), 5-lipooxygenase (24), TNF (25), and cyclin D1 (26), all known to be regulated by nuclear factor-nB (NF-nB).…”

Section: Introductionmentioning

confidence: 99%

Targeting Nuclear Factor-κB Activation Pathway by Thymoquinone: Role in Suppression of Antiapoptotic Gene Products and Enhancement of Apoptosis

Sethi

Ahn

Aggarwal

2008

Molecular Cancer Research

297

218

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Thymoquinone (TQ), derived from the medicinal plant Nigella sativa, exhibits antiinflammatory and anticancer activities through mechanism(s) that is not fully understood. Because numerous effects modulated by TQ can be linked to interference with the nuclear factor-KB (NF-KB) signaling, we investigated in detail the effect of this quinone on NF-KB pathway. As examined by DNA binding, we found that TQ suppressed tumor necrosis factor -induced NF-KB activation in a dose-and time-dependent manner and inhibited NF-KB activation induced by various carcinogens and inflammatory stimuli. The suppression of NF-KB activation correlated with sequential inhibition of the activation of IKBA kinase, IKBA phosphorylation, IKBA degradation, p65 phosphorylation, p65 nuclear translocation, and the NF-KB -dependent reporter gene expression. TQ specifically suppressed the direct binding of nuclear p65 and recombinant p65 to the DNA, and this binding was reversed by DTT. However, TQ did not inhibit p65 binding to DNA when cells were transfected with the p65 plasmid containing cysteine residue 38 mutated to serine. TQ also down-regulated the expression of NF-KB -regulated antiapoptotic (IAP1, IAP2, XIAP Bcl-2, Bcl-xL, and survivin), proliferative (cyclin D1, cyclooxygenase-2, and c-Myc), and angiogenic (matrix metalloproteinase-9 and vascular endothelial growth factor) gene products. This led to potentiation of apoptosis induced by tumor necrosis factor and chemotherapeutic agents. Overall, our results indicate that the anticancer and antiinflammatory activities previously assigned to TQ may be mediated in part through the suppression of the NF-KB activation pathway, as shown here, and thus may have potential in treatment of myeloid leukemia and other cancers.

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Section: Introductionmentioning

confidence: 99%

Targeting Nuclear Factor-κB Activation Pathway by Thymoquinone: Role in Suppression of Antiapoptotic Gene Products and Enhancement of Apoptosis

Sethi

Ahn

Aggarwal

2008

Molecular Cancer Research

297

218

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“…Administration of allicin with CP showed a significant decrease in the level of lung SOD compared to the positive control group, this inhibition could presumably be explained as a consequence of less availability of the substrates for these enzymes (superoxide radical or free radicals) due to the reported superoxide radical scavenging effect (Nagi & Mansour, 2000), as SOD is the only known enzyme that uses free radicals as a substrate.…”

Section: Discussionmentioning

confidence: 96%

Modulation of cyclophosphamide-induced early lung injury by allicin

Ashry

Gameil

Suddеk

2013

Pharmaceutical Biology

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Context: Cyclophosphamide (CP) causes lung injury in rats through its ability to generate free radicals with subsequent epithelial and endothelial cell damage. Objective: This study was conducted to assess whether allicin can ameliorate CP-induced early lung injury in rats. Materials and methods: Male Sprague Dawely rats were divided into four groups. Group I was the control group. Group II received allicin (50 mg/kg/d, p.o.) for 14 consecutive days. Group III was injected once with CP (150 mg/kg, i.p.). Group IV received allicin for seven consecutive days, before and after CP injection (150 mg/kg, i.p.). The parameters of study were serum biomarkers, lung tissue antioxidant profile and histopathological changes in lung tissue. Results: A single intraperitoneal injection of CP markedly altered the levels of several biomarkers in lung homogenates. Significant increases in lung content of lipid hydroperoxides were seen that paralleled the decreased levels of total reduced glutathione. Superoxide dismutase activity (SOD) was significantly increased. CP increased the level of serum biomarkers; total protein, lactate dehydrogenase (LDH) and tumor necrosis factor-alpha (TNF-a). Pretreatment of rats daily with oral allicin seven days prior to and seven days after CP inject significantly inhibited the development of lung injury, prevented the alterations in lung and serum biomarkers associated with inflammatory reactions, with less lipid peroxidation (LP) and restoration of antioxidants. Moreover, allicin attenuated the secretion of proinflammatory cytokine, TNF-a expression in rat serum. In addition, allicin effectively blunted CP-induced histopathological changes in lung tissue. Discussion and conclusion: Our results suggest that allicin is efficient in blunting CP-induced pulmonary damage.

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“…In some previous studies, it has been reported that TQ treatment protected organs against oxidative damage induced by different free radical producing agents like carbon tetrachloride, cisplatin and doxorubicin 8,9 . Different agents with antioxidant, modulators of nitric oxide, diuretic, cytoprotective and antiapoptotic properties have been used to avoid CP nephrotoxicity [10][11][12] .…”

Section: Introductionmentioning

confidence: 99%

Effects of thymoquinone against cisplatin-induced cardiac injury in rats

et al. 2016

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PURPOSE: To investigate the possible protective effect of thymoquinone (TQ) in cisplatin (CP) induced myocardial injury. METHODS:A total of 28 adult male Wistar-Albino rats were randomly and equally divided into four groups as follows: Group 1 (control), Group 2 (CP at 15 mg/kg dose), Group 3 (TQ 40 mg/kg/day for two days prior to CP injection and on third day, CP at 15 mg/kg dose was intraperitoneally administered and TQ treatment continued until fifth day) and Group 4 (TQ at 40mg/kg/day dose for five days). RESULTS:There was a significant increment in CP group in terms of congestion, edema and pycnotic nuclei in myocardial fibers, comparing with other groups. TQ group exhibited significant increase in expression of antiapoptotic protein Bcl-2, comparing with CP group (p<0.05). In only CP administered group, expression of antiapoptotic protein Bcl-2 was lowest comparing with other groups. CONCLUSION:Established data indicate that cisplatin is cardiotoxic and thymoquinone may be useful in treating CP-induced cardiac injury.

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Protective Effect of Thymoquinone Against Doxorubicin–induced Cardiotoxicity in Rats: A Possible Mechanism of Protection

Cited by 266 publications

References 17 publications

Targeting Nuclear Factor-κB Activation Pathway by Thymoquinone: Role in Suppression of Antiapoptotic Gene Products and Enhancement of Apoptosis

Targeting Nuclear Factor-κB Activation Pathway by Thymoquinone: Role in Suppression of Antiapoptotic Gene Products and Enhancement of Apoptosis

Modulation of cyclophosphamide-induced early lung injury by allicin

Effects of thymoquinone against cisplatin-induced cardiac injury in rats

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