title: Radiation protection from whole-body gamma irradiation (6.7 Gy): behavioural effects and brain protein-level changes by an aminothiol compound GL2011 in the Wistar rat.
abstract: GL2011 is a naturally occurring thiol compound and a series of thiol compounds have been proposed as radioprotectors. Radioprotective efficacy of a triple intraperitoneal dose of GL2011 of 100 mg/kg body weight of Wistar rats, 30 min prior to and 3 and 6 h following irradiation (6.7 Gy) was evaluated. Four groups of animals were used, vehicle-treated non-irradiated (VN), GL2011-treated and irradiated (GI), GL2011-treated and non-irradiated (GN) and vehicle-treated and irradiated (VI) (n = 30 per group). The radioprotective efficacy of GL2011 was determined by measuring 28-day survival and intestinal crypt cell survival. Neuroprotection in terms of behaviour was evaluated using the behavioural observational battery, open field test and elevated plus maze paradigm. An RNA microarray was carried out in order to show differences at the RNA level between VI and VN groups. Brain protein changes were identified using a gel-based proteomics method and major brain receptor complex levels were determined by blue-native gels followed by immunoblotting. 28-Day survival rate in VI was 30 %, in GI survival was 93 %, survival of VN and GN was 100 %. Jejunal crypt cell survival was significantly enhanced in GI. Protein-level changes of peroxiredoxin-5, Mn-superoxide dismutase 2, voltage-dependent anion-selective channel protein 1, septin 5 and dopamine D2 receptor complex levels were paralleling radiation damage and protection. Taken together, the findings demonstrate that GL2011 improves survival rates and jejunal crypt survival, provides partial neuroprotection at the behavioural level and modulates proteins known to be involved in protection against oxidative stress-mediated cell damage.
authors.affiliation: Department of Pediatrics, Medical University of Vienna, Wähinger Gürtel 18, 1090, Vienna, Austria, minuganesh87@gmail.com.
authors.forename: Minu Karthika
authors.initials: MK
authors.lastname: Ganesan
authors.forename: Milos
authors.initials: M
authors.lastname: Jovanovic
authors.forename: Bojana
authors.initials: B
authors.lastname: Secerov
authors.forename: Marija
authors.initials: M
authors.lastname: Ignjatovic
authors.forename: Martin
authors.initials: M
authors.lastname: Bilban
authors.forename: Pavle
authors.initials: P
authors.lastname: Andjus
authors.forename: Andjus
authors.initials: A
authors.lastname: Pavle
authors.forename: Amal El
authors.initials: AE
authors.lastname: Refaei
authors.forename: Gangsoo
authors.initials: G
authors.lastname: Jung
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.forename: Ajinkya
authors.initials: A
authors.lastname: Sase
authors.forename: Weiqiang
authors.initials: W
authors.lastname: Chen
authors.forename: Goran
authors.initials: G
authors.lastname: Bacic
authors.forename: Gert
authors.initials: G
authors.lastname: Lubec
mesh_terms: D000588:Amines / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000528:radiation effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D015180:Electrophoresis, Gel, Two-Dimensional; D005720:Gamma Rays / Q000009:adverse effects*; D007274:Injections, Intraperitoneal; D007583:Jejunum / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D018782:Maze Learning; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012313:RNA / Q000032:analysis; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017208:Rats, Wistar; D015203:Reproducibility of Results; D013438:Sulfhydryl Compounds / Q000494:pharmacology*; D015996:Survival Rate; D014916:Whole-Body Irradiation / Q000009:adverse effects*
chemical_list: D000588:Amines; D011506:Proteins; D011837:Radiation-Protective Agents; D013438:Sulfhydryl Compounds; D012313:RNA