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An integrative view of cisplatin-induced renal and cardiac toxicities: Molecular mechanisms, current treatment challenges and potential protective measures
- Source :
- Toxicology. 371
- Publication Year :
- 2016
-
Abstract
- Cisplatin is currently one of the most widely-used chemotherapeutic agents against various malignancies. Its clinical application is limited, however, by inherent renal and cardiac toxicities and other side effects, of which the underlying mechanisms are only partly understood. Experimental studies show cisplatin generates reactive oxygen species, which impair the cell's antioxidant defense system, causing oxidative stress and potentiating injury, thereby culminating in kidney and heart failure. Understanding the molecular mechanisms of cisplatin-induced renal and cardiac toxicities may allow clinicians to prevent or treat this problem better and may also provide a model for investigating drug-induced organ toxicity in general. This review discusses some of the major molecular mechanisms of cisplatin-induced renal and cardiac toxicities including disruption of ionic homeostasis and energy status of the cell leading to cell injury and cell death. We highlight clinical manifestations of both toxicities as well as (novel)biomarkers such as kidney injury molecule-1 (KIM-1), tissue inhibitor of metalloproteinase-1 (TIMP-1) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). We also present some current treatment challenges and propose potential protective strategies including combination therapy with novel pharmacological compounds that might mitigate or prevent these toxicities, which include the use of hydrogen sulfide.
- Subjects :
- 0301 basic medicine
INDUCED CARDIOTOXICITY
Combination therapy
Heart Diseases
Apoptosis
Inflammation
Antineoplastic Agents
Biology
Pharmacology
Toxicology
Bioinformatics
medicine.disease_cause
PHYSIOLOGICAL DISPOSITION
Article
03 medical and health sciences
HIGH-DOSE CISPLATIN
0302 clinical medicine
ENDOPLASMIC-RETICULUM STRESS
medicine
Animals
Humans
OXIDATIVE STRESS
REPERFUSION INJURY
Cisplatin-induced renal and cardiac toxicities
Cisplatin
INDUCED NEPHROTOXICITY
Cardiotoxicity
Kidney
medicine.disease
LIPID-PEROXIDATION
KIDNEY EPITHELIAL-CELLS
030104 developmental biology
medicine.anatomical_structure
030220 oncology & carcinogenesis
Heart failure
Kidney Diseases
medicine.symptom
Reactive oxygen species
Reperfusion injury
GAMMA-GLUTAMYL-TRANSPEPTIDASE
Oxidative stress
medicine.drug
DNA Damage
Subjects
Details
- ISSN :
- 18793185
- Volume :
- 371
- Database :
- OpenAIRE
- Journal :
- Toxicology
- Accession number :
- edsair.doi.dedup.....004fece713e8e45df96e6f8091c3eebe