Taurine protects cisplatin induced cardiotoxicity by modulating inflammatory and endoplasmic reticulum stress responses

Oxidative stress, ER stress, inflammation, and apoptosis results in the pathogenesis of cisplatin‐induced cardiotoxicity. The present study was designed to investigate the signaling mechanisms involved in the ameliorating effect of taurine, a conditionally essential amino acid, against cisplatin‐med...

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Published in:BioFactors (Oxford) 2016-11, Vol.42 (6), p.647-664
Main Authors: Chowdhury, Sayantani, Sinha, Krishnendu, Banerjee, Sharmistha, Sil, Parames C.
Format: Article
Language:English
Subjects:
Animals
Anti-Inflammatory Agents - pharmacology
Anti-Inflammatory Agents - therapeutic use
Antineoplastic Agents - toxicity
Apoptosis - drug effects
Cardiotoxicity - prevention & control
Catalase - metabolism
cisplatin
Cisplatin - toxicity
Dose-Response Relationship, Drug
Drug Evaluation, Preclinical
Endoplasmic Reticulum Stress
heart
Heart Diseases - chemically induced
Heart Diseases - immunology
Heart Diseases - prevention & control
inflammation
Lipid Peroxidation
Male
Mice
Myocardium - enzymology
Myocardium - pathology
oxidative and ER stress
Oxidative Stress - drug effects
Reactive Oxygen Species - metabolism
Superoxide Dismutase - metabolism
taurine
Taurine - pharmacology
Taurine - therapeutic use
Unfolded Protein Response
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Summary:Oxidative stress, ER stress, inflammation, and apoptosis results in the pathogenesis of cisplatin‐induced cardiotoxicity. The present study was designed to investigate the signaling mechanisms involved in the ameliorating effect of taurine, a conditionally essential amino acid, against cisplatin‐mediated cardiac ER stress dependent apoptotic death and inflammation. Mice were simultaneously treated with taurine (150 mg kg−1 body wt, i.p.) and cisplatin (10 mg kg−1 body wt, i.p.) for a week. Cisplatin exposure significantly altered serum creatine kinase and troponin T levels. In addition, histological studies revealed disintegration in the normal radiation pattern of cardiac muscle fibers. However, taurine administration could abate such adverse effects of cisplatin. Taurine administration significantly mitigated the reactive oxygen species production, alleviated the overexpression of nuclear factor‐κB (NF‐κB), and inhibited the elevation of proinflammatoy cytokines, adhesion molecules, and chemokines. Cisplatin exposure resulted in the unfolded protein response (UPR)‐regulated CCAAT/enhancer binding protein (CHOP) up‐regulation, induction of GRP78: a marker of ER stress and eIF2α signaling. Increase in calpain‐1 expression level, activation of caspase‐12 and caspase‐3, cleavage of the PARP protein as well as the inhibition of antiapoptotic protein Bcl‐2 were reflected on cisplatin‐triggered apoptosis. Taurine could, however, combat against such cisplatin induced cardiac‐abnormalities. The above mentioned findings suggest that taurine plays a beneficial role in providing protection against cisplatin‐induced cardiac damage by modulating inflammatory responses and ER stress. © 2016 BioFactors, 42(6):647–664, 2016
ISSN:0951-6433
1872-8081
DOI:10.1002/biof.1301