title: 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.
authors.affiliation: Department of Cancer Chemoprevention, Chittaranjan National Cancer Institute, 37, S. P. Mukherjee Road, Kolkata 700026, West Bengal, India.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Basu
authors.affiliation: Department of Cancer Chemoprevention, Chittaranjan National Cancer Institute, 37, S. P. Mukherjee Road, Kolkata 700026, West Bengal, India.
authors.forename: Prosenjit
authors.initials: P
authors.lastname: Ghosh
authors.affiliation: Department of Cancer Chemoprevention, Chittaranjan National Cancer Institute, 37, S. P. Mukherjee Road, Kolkata 700026, West Bengal, India.
authors.forename: Arin
authors.initials: A
authors.lastname: Bhattacharjee
authors.affiliation: Department of Cancer Chemoprevention, Chittaranjan National Cancer Institute, 37, S. P. Mukherjee Road, Kolkata 700026, West Bengal, India.
authors.forename: Arup Ranjan
authors.initials: AR
authors.lastname: Patra
authors.affiliation: Department of Cancer Chemoprevention, Chittaranjan National Cancer Institute, 37, S. P. Mukherjee Road, Kolkata 700026, West Bengal, India sudinb19572004@yahoo.co.in.
authors.forename: Sudin
authors.initials: S
authors.lastname: Bhattacharya
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000473:pathology; D001855:Bone Marrow Diseases / Q000139:chemically induced / Q000517:prevention & control*; D002869:Chromosome Aberrations / Q000139:chemically induced / Q000187:drug effects*; D002945:Cisplatin / Q000633:toxicity*; D003545:Cysteine / Q000737:chemistry*; D004249:DNA Damage / Q000187:drug effects; D005260:Female; D006801:Humans; D051379:Mice; D009942:Organometallic Compounds / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D014638:Vanadates / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D014638:Vanadates; D003545:Cysteine; D002945:Cisplatin