NOVEL MECHANISM OF ACTION OF CISPLATIN AND ETOPOSIDE THAT MAY PREVENT CARDIAC CELL TOXICITY BY ENHANCING ANTIOXIDANT REDOX STATUS VIA, THE FORMATION OF CISPLATIN AND ETOPOSIDE CONJUGATES AND HYDROGEN PEROXIDE
Pratibha R. Kamble*, Sameer R. Kulkarni and Dayanand A. Bhiwgade
ABSTRACT
Background : Cisplatin and etoposide has a anticancer activity against various types of tumors. Cardiotoxicity by
both drugs is dose dependent. The use of this drugs is often limited due to its side effects that includes silent and
symptomatic arrhythmias. Studies are performed with an aim to study the effect of cisplatin and etoposide on
heart. Methods : Rats were divided into three groups. Group 1 and 2 was injected with 0.4 mg of Cisplatin and,
1.0 mg of Etoposide per kg, i.p daily for 8 weeks. Control rats received 0.5 ml of saline daily. Glutathione (GSH),
Glutathione-S-Transferase (GST), Glutathione Reductase (GR), Glutathione Peroxidase (Gpx), Gamma Glutamyl
Transpeptidase (GGT), Catalase (CAT), Cytochrome p450 (Cyp450) and Lipid peroxidation Lpx (MDA content)
was studied in all three groups. Protein studies were done by SDS-PAGE. Results : Reports obtained from our
studies indicates that Cisplatin and Etoposide increases GSH levels, and GST, GR, GPx, GGT, and Cyp450
activities. Both the drugs at its dose produced an decrease in CAT activity and Lipid peroxidation LPx (MDA
Content) compared to controls. Sirtuin1(SIRT1), a NAD dependent deacetylase in cisplatin and etoposide treated
groups exhibited an increase compared to controls. Conclusions : Cisplatin and Etoposide at low dose shows an
increase in GSH and GSH-dependent enzymes that might protect heart from any oxidative damage. Decrease in
CAT activity and Lpx (MDA content) indicates decrease in free radicals induced cardiotoxic effect. Thus it can
said that drug regimen might replenish NAD+ levels to normal which may protect the heart from any free radical
induced oxidative damage.
Keywords: Cisplatin; Etoposide; Lipid peroxidation; Cardiotoxicity.
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