Biochemical changes associated with ascorbic acid–cisplatin combination therapeutic efficacy and protective effect on cisplatin-induced toxicity in tumor-bearing mice

Abstract

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.

In vivo pharmacokinetic and tissue distribution investigation of sustained-release cisplatin implants in the normal esophageal submucosa of 12 beagle dogs

“…The most sensitive biomarkers with respect to liver cellular damage and toxicity are transaminases, because they are located in the cytoplasm and released into the circulation after cellular damage [30]. Moreover, plasma levels of BUN and creatinine have been reported as markers of platinum toxicity.…”

Ascorbic Acid (Vitamin C)-Mediated Protection on Mutagenic Potentials of Cisplatin in Mice Bearing Ascites Dalton ’s Lymphoma

“…Since cancers may alter the metabolic and endocrine equilibrium in the host (Barbosa et al, 2009), it is reasonable that the ascorbic acid-mediated protective strategies on cisplatin-induced mutagenic effects should be tested in tumor-bearing hosts which may also propose that inspective protective agents are useful in enhancing therapeutic efficacy. Our recent studies have shown that the combination treatment using ascorbic acid with cisplatin show better antitumor activity and reduced tissue toxicities in the hosts (Amenla et al, 2013;Longchar and Prasad, 2015). Thus, the present studies were undertaken to further examine the modulatory effects of combination treatment of cisplatin with ascorbic acid on cisplatin-induced mutagenic potentials in tumor-bearing mice.…”

“…The extent of lipid peroxidation (LPO) was measured in terms of malondialdehyde (MDA) concentration in different tissues of mice using the method of Buege and Aust (1978) as described in detail earlier (Longchar and Prasad, 2015).…”

“…Reduced glutathione and GSH-related enzymes assay: Total glutathione (GSH) was determined in the tissues (liver, kidney and testes) collected from DL-bearing mice under different experimental conditions using the method of Sedlak and Lindsay (1968), as explained and used earlier (Longchar and Prasad, 2015).…”

Synergistic Effect of Vitamin C with Cisplatin for Inhibiting Proliferation of Gastric Cancer Cells

“…This activation may occur by inducing calcium efflux from endoplasmic reticulum, generating reactive oxygen species, reducing adenosine triphosphate production, and stimulating autophagy pathway [6,7] . Further relevant studies have revealed that combining vitamin C with 5-fluorouracil, sodium dascorbate, cyclophosphamide, paclitaxel, arsenic trioxide, doxorubicin, and radiation can sensitize the cancer cells to the exposed anticancer drugs and enhance the success rate of hemo/radiotherapy [8,9] . Indeed, the clinical evaluation confirmed the major positive effect of vitamin C on enhancing the quality of life in 30-95% of cancer patients during chemo/radiotherapy procedures [9] .…”