title: A semiquinone glucoside derivative isolated from Bacillus sp. INM-1 provides protection against 5-fluorouracil-induced immunotoxicity.
abstract: 5-Fluorouracil (5-FU) is a widely used anti-cancer agent; however, it induces immunosuppression in patients undergoing a chemotherapy regime. The mode of action by which 5-FU induces immunosuppression is primarily via inhibition of hematopoietic growth factors. In the present study, immunoprotective effects of a semiquinone glucoside derivative (SQGD), a bacterial metabolite isolated from Bacillus sp. INM-1, were evaluated in a model of 5-FU-induced immunotoxicity in C57Bl/6 male mice. The evaluation was done by analyzing G-CSF, GM-CSF, and M-CSF expression in the serum, spleen, and bone marrow cells of the mice at different timepoints after 5-FU treatment. Mice received a single intraperitoneal injection of either 5-FU (75 mg/kg) alone, SQGD (50 mg/kg) alone, or SQGD 2 h prior to the 5-FU treatment. Control mice received saline vehicle only. The results demonstrated that 5-FU treatment significantly inhibited G-CSF, GM-CSF, and M-CSF expression in all three sites at all timepoints from 6-72 h post 5-FU. In SQGD treated mice, up-regulation of factor expression was observed in each compartment, and significantly so most often after 12 h. SQGD treatment prior to 5-FU administration to the mice significantly increased in all sites evaluated - relative to values in both control mice and 5-FU only-treated mice - G-CSF, M-CSF, and GM-CSF expression at almost every timepoint. The present findings suggest that SQGD provides protection against 5-FU-induced immunotoxicity in mice and could protect bone marrow progenitor cells against the effects of cytotoxic drugs used for treatment of cancer. The findings also suggested to us that SQGD is a potential immunomodulator and could protect hematopoiesis against toxic assault caused by anti-cancer drugs in the clinical setting.
authors: Radiation Biotechnology Laboratory, Department of Radiation Biosciences, Institute of Nuclear Medicine and Allied Sciences , Delhi , India and.
authors: Saurabh
authors: S
authors: Mishra
authors: Poonam
authors: P
authors: Malhotra
authors: Ashutosh K
authors: AK
authors: Gupta
authors: Praveen K
authors: PK
authors: Singh
authors: Saleem
authors: S
authors: Javed
authors: Raj
authors: R
authors: Kumar
mesh_terms: D000818:Animals; D001407:Bacillus / Q000378:metabolism*; D016227:Benzoquinones / Q000008:administration & dosage*; D001853:Bone Marrow / Q000187:drug effects* / Q000378:metabolism; D004358:Drug Therapy; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects; D005960:Glucosides / Q000008:administration & dosage*; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D044967:Serum / Q000187:drug effects* / Q000378:metabolism; D013154:Spleen / Q000378:metabolism
chemical_list: D016227:Benzoquinones; D005960:Glucosides; D016179:Granulocyte Colony-Stimulating Factor; C025232:semiquinone radicals; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D005472:Fluorouracil
keywords: 5-FU; G-CSF; GM-CSF; M-CSF; SQGD