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

Abstract

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.

Modulatory Effect of Rutin on the Antitumor Activity and Genotoxicity of Cisplatin in Tumor-Bearing Mice

“…In the mutagenic/genotoxic bioassays of drugs, one of the best biological indicators includes induction of chromosomal aberrations, micronucleus, and sperm abnormality. 9 , 33 The micronuclei are formed when a fragment of a chromosome is not integrated into one of the daughter cells during the anaphase of the cell division. The results of the micronuclei assay showed that cisplatin alone treatment group significantly increased the occurrence of micronuclei compared to the other treated groups ( Figures 5 and 6 ).…”

“…7,8 To minimize cisplatin-mediated toxicities and resistance, several combination treatments have been used, wherein two or more drugs/agents with different pharmacological properties are often used. [9][10][11] Flavonoids or bioflavonoids are a category of secondary metabolites of plants and fungal origin. Flavonoids possess a wide range of important biological and pharmacological activities which could be very helpful in promoting human health.…”

“… 7 , 8 To minimize cisplatin-mediated toxicities and resistance, several combination treatments have been used, wherein two or more drugs/agents with different pharmacological properties are often used. 9 - 11 …”

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“…In present study, treatment with the combination of rutin and cisplatin showed significant improvement in all the hematological values indicating its potential to reduce cisplatin-induced hematotoxicities (Table 3). In a study Longchar and Prasad [47] reported that combination treatment with ascorbic acid plus cisplatin has better therapeutic efficacy against murine ascites DL in comparison to cisplatin alone treatment and simultaneously helps in the recovery in cisplatininduced hematological values and significant reduction in mutagenic and genotoxic effects [14]. It has been reported that rutin effectively ameliorates the alterations in the hematological parameters through its antioxidant nature [49] and the side-effects of synthetic drugs may be decreased due to flavonoid content in the combinational drugs [50].…”

“…In an attempt to overcome diverse toxicities/side effects caused by cisplatin in the hosts many agents such as phenoxodiol, genistein and gingerol, baicalein, ascorbic acid, naringenin-oxime etc. have been used to lessen toxicities without compromising on its therapeutic efficacy in the hosts [11][12][13][14][15]. Flavonoids, poly-phenolic compounds, are one of the important classes of plant derived chemicals having wide-ranging biological properties including anti-bacterial, antiviral, anti-cancer, anti-inflammatory, hepatoprotective and antioxidant effects [16].…”