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Unraveling the biomechanistic role of Rac1/TWEAK/Fn14/NF-κB intricate network in experimentally doxorubicin-induced cardiotoxicity in rats: The role of curcumin
- Source :
- Journal of biochemical and molecular toxicologyREFERENCES. 35(8)
- Publication Year :
- 2021
-
Abstract
- Doxorubicin (DOX) is an important chemotherapeutic drug. Cardiotoxicity diminishes its clinical efficacy. We aimed to focus on the mechanism of DOX-induced cardiotoxicity, in addition, to evaluate curcumin's protective effect against it. Twenty-eight rats were divided into the normal control group I, curcumin-treated (200 mg/kg body weight [b.w.]) group II, DOX-treated (4 mg/kg b.w.) group III, and DOX + curcumin group IV. Cardiac injury markers, heart tissue oxidative stress indices, interferon-gamma (INF-γ), tumor necrosis factor-like weak inducer of apoptosis (TWEAK), upregulated modulator of apoptosis (PUMA), p53 and nuclear factor kappa-B p65 (NF-κB p65) levels as well as messenger RNA gene expression of Rac1 and fibroblast growth factor-inducible protein 14 (Fn14) were assayed, besides the assay of DNA damage, histopathological changes, survivin immunohistochemistry and electron microscopic examination. Curcumin significantly downregulated Rac1 and Fn14 gene expression and significantly decreased p53, NF-κB p65, INF-γ, and PUMA levels in the cardiac tissue. In addition, curcumin improved oxidative stress indices, DNA damage, and cardiac toxicity markers in the form of lactate dehydrogenase (LD), creatine kinase isoenzyme-MB (CK-MB), and cardiac troponin-I (cTn-I). Meanwhile, upregulated antiapoptotic marker survivin was observed. Light and electron microscopic findings confirmed our biochemical and molecular outcomes. The current study established the antioxidant, anti-inflammatory, and antiapoptotic roles of curcumin against DOX cardiotoxicity.
- Subjects :
- 0301 basic medicine
Male
rac1 GTP-Binding Protein
Curcumin
DNA damage
Health, Toxicology and Mutagenesis
Pharmacology
Toxicology
medicine.disease_cause
Biochemistry
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Puma
Survivin
medicine
Animals
Doxorubicin
Molecular Biology
Cardiotoxicity
030102 biochemistry & molecular biology
biology
Chemistry
NF-kappa B
Cytokine TWEAK
General Medicine
biology.organism_classification
Rats
Apoptosis
TWEAK Receptor
030220 oncology & carcinogenesis
Molecular Medicine
Oxidative stress
medicine.drug
Signal Transduction
Subjects
Details
- ISSN :
- 10990461
- Volume :
- 35
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Journal of biochemical and molecular toxicologyREFERENCES
- Accession number :
- edsair.doi.dedup.....604622c1a4cb8d1fc21562d7c6fa6cd0