Dietary Ascorbic Acid-Mediated Augmentation of Antitumor Activity and Protection Against Toxicities Induced by Cis-Diamminedichloroplatinum-(II) in Dalton’s Lymphoma-Bearing Mice
Pages 116-130
Amenla, Akalesh Kumar Verma and Surya Bali Prasad

DOI: http://dx.doi.org/10.6000/1929-2279.2013.02.02.6

Published: 30 April 2013 

Abstract: Cis-Diamminedichloroplatinum-(II) (CDDP) commonly known as cisplatin is considered as a major anticancer drug against a broad spectrum of malignancies. This study evaluates the modulatory effect of dietary ascorbic acid (AA) on the therapeutic efficacy of CDDP against murine ascites Dalton’s lymphoma (DL) and some tissue toxicities in tumor-bearing mice.

As compared to CDDP alone, the combination treatment with ascorbic acid (AA) plus CDDP showed better therapeutic efficacy against murine ascites Dalton’s lymphoma. DL cells treated with CDDP showed the appearance of apoptotic features involving fragmentation of nucleus into discrete masses and plasma membrane blebbing. As compared to CDDP alone, combination treatment caused an increase in the number of apoptotic DL cells. Reduced glutathione (GSH) level was noted to decrease in DL cells while it increased in kidney after combination treatment. Blood haemoglobin (Hb), red blood cells (RBCs) and white blood cells (eosinophils, basophils and lymphocytes) were also decreased after CDDP treatment while overall betterment in hematological parameters was noted after combination treatment. The analysis of renal function tests (RFT) and liver function tests (LFT) suggest an improvement against CDDP-induced liver and kidney toxicities after combination treatment.

The decrease in GSH levels particularly in DL cells and an increase in kidney and liver after combination treatment may have a role in the antitumor activity and decrease in CDDP-induced toxicity in the tumor-bearing host. Improvement in the LFT, RFT and hematological toxicities after combination treatment may have a beneficial effect in the improved survival of tumor-bearing mice.