title: An oxovanadium(IV) complex protects murine bone marrow cells against cisplatin-induced myelotoxicity and DNA damage.
abstract: Cisplatin (CDDP) is one of the first-line anticancer drugs that has gained widespread use against various forms of human malignancies. But, the therapeutic outcome of CDDP therapy is limited due to its adverse effects including myelotoxicity and DNA damage which may lead to the subsequent risk of developing secondary cancer. Hence, in search of a suitable cytoprotectant, this study investigated the probable protective efficacy of an oxovanadium(IV) complex, namely oxovanadium(IV)-L-cysteine methyl ester complex (VC-IV) against CDDP-induced myelosuppression and genotoxic damage in the bone marrow cells of Swiss albino mice. CDDP was administered intraperitoneally (5 mg/kg b.w.) and VC-IV was administered orally (1 mg/kg b.w.) in concomitant and 7 d pretreatment schedule. Treatment with VC-IV in CDDP-treated mice significantly (p < 0.01) enhanced bone marrow cell proliferation and inhibited cell death in the bone marrow niche indicating improvement of CDDP-induced myelotoxicity. The organovanadium compound also significantly (p < 0.01) reduced the percentage of chromosomal aberrations, the frequency of micronuclei formation, and the extent of DNA damage. The observed chemoprotective effect of VC-IV was attributed to its anti-oxidant efficacy which significantly (p < 0.01) attenuated CDDP-induced generation of free radicals, and restored (p < 0.01) the levels of oxidized and reduced glutathione. Hence, VC-IV may serve as a promising candidate for future development to decrease the deleterious effects of CDDP in the bone marrow cells of cancer patients and associated secondary complications.
authors.affiliation: a Department of Cancer Chemoprevention , Chittaranjan National Cancer Institute , Kolkata, West Bengal , India and.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Basu
authors.affiliation: a Department of Cancer Chemoprevention , Chittaranjan National Cancer Institute , Kolkata, West Bengal , India and.
authors.forename: Arin
authors.initials: A
authors.lastname: Bhattacharjee
authors.affiliation: b Division of Microbiology , Department of Pharmaceutical Technology, Jadavpur University , Kolkata, West Bengal , India.
authors.forename: Amalesh
authors.initials: A
authors.lastname: Samanta
authors.affiliation: a Department of Cancer Chemoprevention , Chittaranjan National Cancer Institute , Kolkata, West Bengal , India and.
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*; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity*; D020552:Comet Assay; D003545:Cysteine / Q000031:analogs & derivatives / Q000737:chemistry; D004249:DNA Damage / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D051379:Mice; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced; D015162:Micronucleus Tests; D009942:Organometallic Compounds / Q000737:chemistry / Q000627:therapeutic use*; D020011:Protective Agents / Q000737:chemistry / Q000627:therapeutic use*; D014638:Vanadates / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D020011:Protective Agents; C075743:oxovanadium IV; D014638:Vanadates; D003545:Cysteine; D002945:Cisplatin; C017507:mecysteine
keywords: Chemotherapy; DNA damage; apoptosis; clastogenicity; oxidative stress; vanadium