In vitro radioprotection studies of organoselenium compounds: differences between mono- and diselenides.
Organoselenium compounds belonging to the class of monoselenides, such as selenomethionine (SeM) and methylselenocysteine (MSeCys) and diselenides including selenocystine (SeCys) and selenopropionic acid (SePA), were examined for their comparative radioprotective effects using in vitro models. Effects of these compounds on the inhibition of gamma-radiation induced lipid peroxidation in liposomes, protein carbonylation in bovine serum albumin (BSA) and strand breaks in pBR322 plasmid DNA, assessed, respectively, by the formation of thiobarbituric acid reactive substances, formation of 2,2'-dinitrophenyl hydrazine (DNPH) carbonyl complex and horizontal gel electrophoresis, were used to compare their radioprotective ability. The IC 50 values for SeCys, SePA, SeM and MSeCys for lipid peroxidation were 27 +/- 1, 33 +/- 2, 200 +/- 8 and 163 +/- 4 microM, respectively, and the values for inhibition of protein carbonylation were >200, 300 +/- 6, 464 +/- 8 and 436 +/- 3 microM, respectively. Inhibition of DNA strand break formation was tested at 200 microM for all the compounds and SePA and SeCys exhibited a protective effect on DNA, while SeM and MSeCys did not lead to any protection. The in vitro cytotoxicity studies in normal and tumor cells revealed that MSeCys and SeM were not cytotoxic to lymphocytes and EL4 tumor cells at the concentrations employed. In contrast, SeCys was toxic, with a higher effect on tumor cells than lymphocytes. Our studies suggest that the non-toxic diselenides like SePA should be explored as protective agents against gamma-irradiation induced damage.
Kumar
B Santhosh
BS
Department of Physiology, Deccan College of Medical Sciences, Hyderabad, India. santhosh910@rediffmail.com
Kunwar
Amit
A
Ahmad
A
A
Kumbhare
L B
LB
Jain
V K
VK
Priyadarsini
K I
KI
D000818:Animals; D002417:Cattle; D045744:Cell Line, Tumor; D003545:Cysteine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D003553:Cystine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D004247:DNA / Q000737:chemistry / Q000187:drug effects / Q000528:radiation effects; D004249:DNA Damage / Q000187:drug effects / Q000528:radiation effects; D005720:Gamma Rays / Q000009:adverse effects; D015227:Lipid Peroxidation / Q000187:drug effects / Q000528:radiation effects; D008081:Liposomes / Q000737:chemistry / Q000528:radiation effects; D008214:Lymphocytes / Q000187:drug effects / Q000528:radiation effects; D008223:Lymphoma / Q000188:drug therapy / Q000532:radiotherapy; D051379:Mice; D008810:Mice, Inbred C57BL; D016566:Organoselenium Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D050050:Protein Carbonylation / Q000187:drug effects / Q000528:radiation effects; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D017279:Selenocysteine / Q000031:analogs & derivatives; D012645:Selenomethionine / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D012710:Serum Albumin, Bovine / Q000187:drug effects / Q000528:radiation effects; D017392:Thiobarbituric Acid Reactive Substances / Q000737:chemistry; D013953:Thymus Neoplasms / Q000188:drug therapy / Q000532:radiotherapy
D008081:Liposomes; D016566:Organoselenium Compounds; D011837:Radiation-Protective Agents; D017392:Thiobarbituric Acid Reactive Substances; D017279:Selenocysteine; C009226:selenocystine; D012710:Serum Albumin, Bovine; D003553:Cystine; D004247:DNA; D012645:Selenomethionine; D003545:Cysteine; C002979:selenomethylselenocysteine