Cisplatin is one of the well-established anticancer drugs being used against a wide spectrum of cancers. However, full therapeutic efficacy of the drug is limited due to development of various toxicities in the host. This study examines the comparative therapeutic effectiveness and toxicities of cisplatin alone and in combination of dietary ascorbic acid (AA) in ascites Dalton's lymphoma-bearing mice. The findings show that the combination treatment of mice with ascorbic acid plus cisplatin has much better therapeutic efficacy against murine ascites Dalton's lymphoma (DL) in comparison to cisplatin alone and this may involve a decrease in reduced glutathione (GSH), catalase activity and increased lipid peroxidation (LPO) in Dalton's lymphoma tumor cells. At the same time, combination treatment indicates a protective role of ascorbic acid against cisplatin-induced tissue toxicities (side effects) in the hosts. Cisplatin-induced histopathological changes in liver, kidney and testes were decreased after combination treatment. The analysis of renal function test (RFT), liver function test (LFT) and sperm abnormalities also suggest an improvement in these parameters after combination treatment. Therefore, it may be concluded that the increased GSH level, catalase activity and decreased LPO in the tissues, i.e., liver, kidney and testes after combination treatment may be involved in its protective ability against cisplatin-induced tissue toxicities in the host.

Cisplatin is a potent anticancer drug which has been in use against a variety of cancers for a long time. The present study was carried out to assess the protective ability of ascorbic acid on cisplatin-induced mutagenic effects in tumor-bearing mice. The increase in the frequency of chromosomal aberrations, micronuclei and sperm abnormality were studied as markers of mutagenicity. Indicators of oxidative stress relatives like lipid peroxidation, reduced glutathione and the activities of enzymes such as catalase, glutathione-S-transferase and glutathione reductase were also studied to understand the possible mechanism(s) underlying this amelioration. Pre-treatment with ascorbic acid in combination group significantly reduced cisplatin-induced mutagenicity, markedly decreased lipid peroxidation along with increased level of glutathione and activities of antioxidant enzymes particularly in the liver of mice. The overall studies suggest that ascorbic acid with its antioxidant and free radical scavenging properties may play a part in its protective role in the abatement of cisplatin-induced mutagenesis and oxidative damage in the normal tissues of mice.

Cisplatin treatment caused a significant increase in the life span of ascites Dalton's lymphoma (DL) Tumor-bearing (TB) mice. However, as compared to cisplatin (CP) alone, combination treatment with ascorbic acid plus CP resulted in better therapeutic efficacy against murine DL. Cisplatin treatment of TB mice resulted in the appearance of thickened and irregular arrangement of mitochondrial cristae in the liver, kidney and DL tumor cells. Combination treatment of the hosts with ascorbic acid and CP lessened deformities in the mitochondria of liver and kidney, while in tumor cells, this increased the formation of vacuoles and disruption in mitochondrial cristae. Cisplatin treatment decreased the succinate dehydrogenase (SDH) activity in the mitochondria of kidney and DL cells and combination treatment caused further decrease in SDH activity in kidney and DL cells during 24-48 h of treatment. After CP treatment, the protein content in the mitochondria of these tissues decreased, and during combination treatment, it showed significant improvement. Mitochondrial lipid peroxidation (LPO) increased in these tissues after CP treatment. However, combination treatment significantly decreased mitochondrial LPO in liver and kidney but increased in DL cells. This increase in mitochondrial LPO in DL cells and decrease in liver and kidney could play an important role in the antitumor activity of combination treatment and at the same time reduce CP-induced toxicity in the host. However, further study may be desirable to explore some aspects of the mechanism(s) involved in these changes in mitochondria.