Antioxidant action of bixin against cisplatin-induced chromosome aberrations and lipid peroxidation in rats.

The use of dietary antioxidants to prevent antitumor agent-induced chromosomal damage in nontumor cells is currently eliciting considerable interest. Curcumin (CMN) is a dietary antioxidant that has been reported to protect against clastogenesis in in vivo and in vitro assays. This study was undertaken to investigate the modulatory effects of CMN on cisplatin-induced chromosomal aberrations in Wistar rat bone marrow cells and whether there is any potentiation of these effects with the combination between CMN and vitamin C (VC), which has been reported to reduce the clastogenic effect of many antitumor agents in in vivo assays. Animals treated with CMN plus a single dose of cisplatin, at 18, 24 or 72 h following treatment, presented a statistically significant reduction in the total amount of chromosomal damage and in the number of abnormal metaphases. The results also indicate that the combination between antioxidants would not be effective in protecting against cisplatin-induced chromosomal damage in animals sacrificed 24 h after cisplatin treatment. Under the present experimental conditions, CMN could prevent cisplatin-induced clastogenesis by acting as a free radical scavenger.

Effects of the antioxidants curcumin and vitamin C on cisplatin-induced clastogenesis in Wistar rat bone marrow cells

The aim of the present investigation is to determine whether the quercetin in combination with cisplatin can ameliorate cisplatin-induced clastogenesis and apoptosis in the bone marrow cells of mice. The scoring of chromosomal aberrations, micronuclei and mitotic activity were undertaken in the current study as markers of clastogenicity. Apoptosis was analysed by the Annexin V-propidium iodide assay and the occurrence of a hypodiploid DNA peak. Oxidative stress markers such as bone marrow lipid peroxidation and reduced glutathione were assessed as a possible mechanism underlying this amelioration. Quercetin was neither clastogenic nor apoptogenic in mice at doses equivalent to 50 or 100 mg/kg for 2 days. Pre-treatment of mice with quercetin significantly reduced cisplatin-induced clastogenesis and apoptosis in the bone marrow cells and these effects were dose and time dependent. Prior administration of quercetin ahead of cisplatin challenge ameliorated oxidative stress markers. Overall, this study provides for the first time that quercetin has a protective role in the abatement of cisplatin-induced clastogenesis and apoptosis in the bone marrow cells of mice that resides, at least in part, in its antioxidant effects. Therefore, quercetin can be a good candidate to decrease the deleterious effects of cisplatin in the bone marrow cells of cancer patients treated with this drug.

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The impact of quercetin on cisplatin-induced clastogenesis and apoptosis in murine marrow cells

Antigenotoxic and anticytotoxic effect of camel milk in mice treated with cisplatin

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.

Sensitization of cisplatin therapy by a naphthalimide based organoselenium compound through modulation of antioxidant enzymes and p53 mediated apoptosis.

The clastogenic effect of the drug cis-diamminedichloroplatinum II (cisplatin, CDDP) was investigated in Wistar rat bone marrow cells. Male rats, 3 per treatment time, aged 4 months and weighing 250-350 g were injected intraperitoneally with 6.0 mg/kg CDDP solution, and the control group received isotonic saline. The animals were sacrificed 6, 12, 18, 24 and 48 h after the injection. The chromosome preparation was obtained from bone marrow cells. Chromatid and chromosome aberrations were investigated in 300 metaphases per animal. A significant increase in number of chromosome aberrations was observed from 6 to 24 h, the majority being of the break and gap type. After 48 h a progressive reduction was observed, without differences from the negative control. These data confirm the mutagenic effect of CDDP in rats demonstrated for mice bone marrow by micronuclei assay, for murine ovary cells and mice spermatocytes.

H.M. Lizardo-Daudt

Papers

Clastogenic effect of cisplatin on Wistar rat bone marrow cells.