title: Possible modulating impact of glutathione disulfide mimetic on physiological changes in irradiated rats.
abstract: Glutathione disulfide mimetic (NOV-002) is a complex of oxidized glutathione (GSSG) formulated with cisplatin at approximately 1000:1 molar ratio. Cisplatin serves to stabilize GSSG but does not assert any therapeutic effect. The objective of this study is to evaluate the impact of NOV-002 on hematological suppression, excessive free radical damage and DNA fragmentation in splenocytes, and metabolite disorders in whole-body γ-irradiated rats. The obtained data revealed that rats treated with 25 mg kg(-1) NOV-002 injected intraperitoneally (i.p.) for 5 days after whole-body γ-irradiation (IR) at 6.5 Gy attenuated the decrease of red blood cells, platelets, total white blood cells, absolute lymphocytes and neutrophils counts, hematocrit value, and hemoglobin content. NOV-002 treatment inhibits serum advanced oxidation protein products, malondialdehyde concentrations as well as cholesterol, triglycerides, urea, and creatinine levels, while enhances glutathione content and superoxide dismutase activity and improves DNA fragmentation in splenocytes. These findings provide a better understanding of the NOV-002 modulating impact in whole-body γ-rays-induced hematological toxicities, oxidative stress, and biological disturbances in γ-irradiated rats and could enhance the tolerance to high doses of ionizing IR utilized in radiotherapy.
authors.affiliation: Department of Radiation Biology, National Centre for Radiation Research and Technology (NCRRT), Nasr City, Cairo, Egypt safwatfaried@hotmail.com.
authors.forename: S F
authors.initials: SF
authors.lastname: Salama
authors.affiliation: Department of Radiation Biology, National Centre for Radiation Research and Technology (NCRRT), Nasr City, Cairo, Egypt.
authors.forename: S A
authors.initials: SA
authors.lastname: Montaser
mesh_terms: D000818:Animals; D002452:Cell Count; D002945:Cisplatin / Q000494:pharmacology*; D053938:DNA Fragmentation; D004338:Drug Combinations; D005720:Gamma Rays / Q000009:adverse effects*; D019803:Glutathione Disulfide / Q000494:pharmacology*; D006400:Hematocrit; D006454:Hemoglobins / Q000032:analysis; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D051381:Rats; D013154:Spleen / Q000166:cytology; D014916:Whole-Body Irradiation
chemical_list: D004338:Drug Combinations; D006454:Hemoglobins; C529375:NOV 002; D011837:Radiation-Protective Agents; D002945:Cisplatin; D019803:Glutathione Disulfide
keywords: DNA fragmentation; NOV-002; metabolites; oxidative stress; γ-rays