Sensitization of cisplatin therapy by a naphthalimide based organoselenium compound through modulation of antioxidant enzymes and p53 mediated apoptosis

Autor:	S. K. Bhattacharya, Somnath Singha Roy, Arin Bhattacharjee, Prokash Ghosh, Arnab Basu
Rok vydání:	2015
Předmět:	DNA damage Apoptosis Pharmacology Kidney medicine.disease_cause Biochemistry Antioxidants Ehrlich ascites carcinoma Nephrotoxicity Lipid peroxidation Mice chemistry.chemical_compound Organoselenium Compounds Antineoplastic Combined Chemotherapy Protocols medicine Animals Anticarcinogenic Agents Carcinoma Ehrlich Tumor Chromosome Aberrations Cisplatin chemistry.chemical_classification Reactive oxygen species General Medicine Naphthalimides Oxidative Stress chemistry Female Tumor Suppressor Protein p53 Oxidative stress DNA Damage medicine.drug
Zdroj:	Free Radical Research. 49:453-471
ISSN:	1029-2470 1071-5762
DOI:	10.3109/10715762.2015.1012079
Popis:	The widely used anti-cancer drug cisplatin imparts various toxic manifestations in the host, with nephrotoxicity being the most severe one. The trace element selenium shows antioxidant activity in both human and animals. The present study was designed to assess the chemoprotecting and chemoenhancing efficacy of a naphthalimide based organoselenium compound 2-(5-selenocyanato-pentyl)-benzo[de]isoquinoline 1,3-dione during cisplatin chemotherapy in mice bearing Ehrlich ascites carcinoma cells. Cisplatin (5 mg/kg b.w.) was administered intraperitoneally and the organoselenium compound (3 mg/kg b.w.) was given by oral gavage in concomitant and pretreatment schedule. The effects of the test compound was evaluated by assaying biochemical, hematological, histological, genotoxicity parameters and by investigating induction of apoptosis in tumor cells, and calculating tumor growth response in the host. The organoselenium compound significantly prevented cisplatin induced generation of reactive oxygen species (ROS), reactive nitrogen species, and onset of lipid peroxidation in the kidney tissue of the experimental mice. In addition, the test compound was also substantially restored cisplatin induced depleted activities of the renal antioxidant enzymes and reduced glutathione level; prevented the serum blood urea nitrogen level, creatinine level, chromosomal aberration, DNA damage, histological alterations of kidney, and normalized the hematological profile of the tumor bearing mice. Furthermore, the organoselenium compound alone or during combination therapy induced apoptosis in tumor cells through mitochondria mediated and DNA damage mediated pathway and ultimately increased the life span of the tumor bearing host. Hence, the results showed that the test compound not only reduced the toxicity of cisplatin but also enhanced its anti-tumor efficacy.
Databáze:	OpenAIRE
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