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.