PMID- 24512327 OWN - NLM STAT- MEDLINE DCOM- 20150930 LR - 20141219 IS - 1547-6901 (Electronic) IS - 1547-691X (Linking) VI - 12 IP - 1 DP - 2015 Jan-Mar TI - A semiquinone glucoside derivative isolated from Bacillus sp. INM-1 provides protection against 5-fluorouracil-induced immunotoxicity. PG - 56-63 LID - 10.3109/1547691X.2014.882448 [doi] AB - 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. FAU - Mishra, Saurabh AU - Mishra S AD - Radiation Biotechnology Laboratory, Department of Radiation Biosciences, Institute of Nuclear Medicine and Allied Sciences , Delhi , India and. FAU - Malhotra, Poonam AU - Malhotra P FAU - Gupta, Ashutosh K AU - Gupta AK FAU - Singh, Praveen K AU - Singh PK FAU - Javed, Saleem AU - Javed S FAU - Kumar, Raj AU - Kumar R LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140210 PL - England TA - J Immunotoxicol JT - Journal of immunotoxicology JID - 101201960 RN - 0 (Benzoquinones) RN - 0 (Glucosides) RN - 143011-72-7 (Granulocyte Colony-Stimulating Factor) RN - 3225-29-4 (semiquinone radicals) RN - 81627-83-0 (Macrophage Colony-Stimulating Factor) RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) RN - U3P01618RT (Fluorouracil) SB - IM MH - Animals MH - Bacillus/*metabolism MH - Benzoquinones/*administration & dosage MH - Bone Marrow/*drug effects/metabolism MH - Drug Therapy MH - Fluorouracil/adverse effects/therapeutic use MH - Gene Expression Regulation/drug effects MH - Glucosides/*administration & dosage MH - Granulocyte Colony-Stimulating Factor/genetics/metabolism MH - Granulocyte-Macrophage Colony-Stimulating Factor/genetics/metabolism MH - Hematopoiesis/drug effects MH - Humans MH - Macrophage Colony-Stimulating Factor/genetics/metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Serum/*drug effects/metabolism MH - Spleen/metabolism OTO - NOTNLM OT - 5-FU OT - G-CSF OT - GM-CSF OT - M-CSF OT - SQGD EDAT- 2014/02/12 06:00 MHDA- 2015/10/01 06:00 CRDT- 2014/02/12 06:00 PHST- 2014/02/12 06:00 [entrez] PHST- 2014/02/12 06:00 [pubmed] PHST- 2015/10/01 06:00 [medline] AID - 10.3109/1547691X.2014.882448 [doi] PST - ppublish SO - J Immunotoxicol. 2015 Jan-Mar;12(1):56-63. doi: 10.3109/1547691X.2014.882448. Epub 2014 Feb 10.