Prevention of myelosuppression and genotoxicity induced by cisplatin in murine bone marrow cells: effect of an organovanadium compound vanadium(III)-l-cysteine

Abstract

Cisplatin (CDDP) is one of the first-line anticancer drugs indicated for use against various form of human malignancies; but, the therapeutic outcome of CDDP chemotherapy is limited due to the development of myelosuppression and genotoxicity which may lead to secondary cancer. Induction of oxidative stress in normal host cells is thought to be responsible for these adverse effects. Therefore, in search of a potential chemoprotectant, an oraganovanadium compound, viz., vanadium(III)-l-cysteine (VC-III) was evaluated against CDDP-induced clastogenicity and cytotoxicity in bone marrow cells of Swiss albino mice. CDDP was administered intraperitoneally (5mg/kg body weight [b.w.]) and VC-III was given by oral gavage (1mg/kg b.w.) in concomitant and pretreatment schedule. The results showed that VC-III administration significantly (P < 0.001) enhanced cell proliferation and inhibited apoptosis in the bone marrow niche indicating recovery of CDDP-induced myelosuppression. VC-III also significantly (P < 0.001) decreased the percentage of chromosomal aberrations, the frequency of micronuclei formation and the extent of DNA damage. The observed antigenotoxic and cytoprotective effect of VC-III was attributed to its attenuation of free radicals status and restoration of oxidised and reduced glutathione levels. These results suggest that VC-III is a potential candidate for future development as a chemoprotective agent against chemotherapy-associated primary and secondary complications.

Genetic and Modifiable Risk Factors Contributing to Cisplatin-induced Toxicities

“…Cisplatin-based therapy often has a disproportionate effect on erythrocyte production in comparison with other blood cells, resulting in a cumulative, clinically significant anemia (67). The increase in oxidative stress that induces other cisplatin-induced adverse sequelae (Table 1) also appears to contribute to bone marrow toxicity (68). While acute myelosuppression is an immediate clinical concern, many patients receiving chemotherapy and/or radiotherapy also develop residual bone marrow injury, as evidenced by a sustained reduction in hematopoietic stem cell reserves that can potentiate long-term hematologic complications (69,70).…”

Pituranthos chloranthus Oil as an Antioxidant-Based Adjuvant Therapy against Cisplatin-Induced Nephrotoxicity

“…Intracellular ROS production was measured with the help of oxidative fluorescent probe DCFH-DA. Cells (5 × 10 5 ) were stained with 10 μM DCFH-DA and incubated in the dark for 30 min to allow the formation of fluorescent dichlorofluorescein (DCF) and then analyzed using a fluorescence microplate reader (Biotek, Winooski, USA), with 538 nm emission and at 485 nm excitation filters [15].…”

FASandFASLvariations in outcomes of tobacco- and alcohol-related head and neck squamous cell carcinoma patients

“…It is already known that CDDP may induce a deep transient erythropoiesis alteration leading to anemia. 47,48 CDDP inhibits bone marrow cell proliferation by DNA damage, 49 possibly due to apoptosis induced by FAS activation. 9 Because the allele G of FAS c.671A > G was previously associated with lower apoptosis of damaged cells, 13 these results were not expected by us.…”