title: Dihydroxyselenolane (DHS) supplementation improves survival following whole-body irradiation (WBI) by suppressing tissue-specific inflammatory responses.
abstract: Dihydroxyselenolane (DHS), a simple water-soluble organoselenium compound, was evaluated for radioprotection in BALB/c mice after whole-body irradiation (WBI) (8Gy (60)Co, 1Gy/min), by monitoring 30-d post-irradiation survival and biochemical/histological changes in radiosensitive organs. Intraperitoneal administration of DHS at 2mg/kg for five consecutive days before irradiation and three times per week during the post-irradiation period showed maximum benefit (40% improvement in 30 d post-irradiation survival). DHS treatment, despite inducing expression of glutathione peroxidases (GPx1, GPx2, and GPx4) in spleen and intestine, did not protect against radiation-induced acute (10-day) haematopoietic and gastrointestinal toxicities. DHS treatment significantly reduced radiation-induced DNA damage in peripheral leukocytes and inflammatory responses in intestine, lung, and circulation. The anti-inflammatory effect of DHS was associated with reductions in lipid peroxidation, expression of pro-inflammatory genes such as Icam-1, Ccl-2, and iNos-2, and subsequent infiltration of inflammatory cells. Irradiated mice treated with DHS survived until day 30 post-irradiation and showed restoration of spleen cellularity and intestinal villi, but had moderately increased systemic and tissue-specific inflammatory responses. Another organoselenium compound, selenomethionine, evaluated in parallel with DHS at the same dose and treatment schedule, showed comparable radioprotective effects. The mechanism of radioprotection by DHS is mainly via suppression of inflammatory responses.
authors.affiliation: Radiation and Photochemistry Division, Bhabha Atomic Research Centre, Mumbai 400085, India. Electronic address: kamit@barc.gov.in.
authors.forename: Amit
authors.initials: A
authors.lastname: Kunwar
authors.affiliation: Radiation and Photochemistry Division, Bhabha Atomic Research Centre, Mumbai 400085, India; Homi Bhabha National Institute, Bhabha Atomic Research Centre, Mumbai 400094, India.
authors.forename: Prachi
authors.initials: P
authors.lastname: Verma
authors.affiliation: Radiation Biology & Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400085, India.
authors.forename: H N
authors.initials: HN
authors.lastname: Bhilwade
authors.affiliation: Department of Chemistry, Tokai University, Kitakaname, Hiratsuka-shi, Kanagawa 259-1292, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Iwaoka
authors.affiliation: Radiation and Photochemistry Division, Bhabha Atomic Research Centre, Mumbai 400085, India; Homi Bhabha National Institute, Bhabha Atomic Research Centre, Mumbai 400094, India. Electronic address: kindira@barc.gov.in.
authors.forename: K Indira
authors.initials: KI
authors.lastname: Priyadarsini
mesh_terms: D054508:Acute Radiation Syndrome / Q000188:drug therapy* / Q000517:prevention & control; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D007274:Injections, Intraperitoneal; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects / Q000528:radiation effects; D015227:Lipid Peroxidation; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D009928:Organ Specificity; D016566:Organoselenium Compounds / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D014916:Whole-Body Irradiation / Q000009:adverse effects*
chemical_list: C000614111:3,4-dihydroxyselenolane; D000893:Anti-Inflammatory Agents; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D016566:Organoselenium Compounds; D011837:Radiation-Protective Agents; D018799:Intercellular Adhesion Molecule-1; D005979:Glutathione Peroxidase; D052247:Nitric Oxide Synthase Type II
keywords: Dihydroxyselenolane; Glutathione peroxidase; Inflammation; Radioprotector; Selenomethionine