title: Effects of N-acetylcysteine amide (NACA), a thiol antioxidant on radiation-induced cytotoxicity in Chinese hamster ovary cells.
abstract: Ionizing radiation is known to cause tissue damage in biological systems, mainly due to its ability to produce reactive oxygen species (ROS) in cells. Many thiol antioxidants have been used previously as radioprotectors, but their application has been limited by their toxicity. In this investigation, we have explored the possible radioprotective effects of a newly synthesized thiol antioxidant, N-acetylcysteine amide (NACA), in comparison with N-acetylcysteine (NAC), a commonly used antioxidant. Protective effects of NACA and NAC were assessed using Chinese hamster ovary (CHO) cells, irradiated with 6 gray (Gy) radiation. Oxidative stress parameters, including levels of reduced glutathione (GSH), cysteine, malondialdehyde (MDA), and activities of antioxidant enzymes like glutathione peroxidase, glutathione reductase, and catalase, were measured. Results indicate that NACA was capable of restoring GSH levels in irradiated cells in a dose dependent manner. In addition, NACA prevented radiation-induced loss in cell viability. NACA further restored levels of malondialdehyde, caspase-3 activity, and antioxidant enzyme activities to control levels. Although NAC affected cells in a similar manner to NACA, its effects were not as significant. Further, NAC was also found to be cytotoxic to cells at higher concentrations, whereas NACA was non-toxic at similar concentrations. These results suggest that NACA may be able to attenuate radiation-induced cytotoxicity, possibly by its ability to provide thiols to cells.
authors.affiliation: Department of Chemistry, Missouri University of Science and Technology, 1870 Miner Circle, Rolla, MO 65409, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Linu
authors.initials: L
authors.lastname: Abraham
authors.forename: Joshua
authors.initials: J
authors.lastname: Ogony
authors.forename: Richard
authors.initials: R
authors.lastname: Matthews
authors.forename: Glenn
authors.initials: G
authors.lastname: Goldstein
authors.forename: Nuran
authors.initials: N
authors.lastname: Ercal
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D016466:CHO Cells; D053148:Caspase 3 / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects* / Q000528:radiation effects*; D006224:Cricetinae; D003412:Cricetulus; D003545:Cysteine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000528:radiation effects; D011837:Radiation-Protective Agents
chemical_list: D000975:Antioxidants; D011837:Radiation-Protective Agents; C487056:N-Acetylcysteinamide; D008315:Malondialdehyde; D002374:Catalase; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D053148:Caspase 3; D005978:Glutathione; D003545:Cysteine; D000111:Acetylcysteine