title: Evaluation of AL-05712 and AL-05741 as thioltransferase mimics for the prevention and recovery of pre-cataractous changes in lens.
abstract: It has been previously shown that during the aging process, the human eye lens accumulates protein-glutathione mixed disulfides (PSSG) and that the reduced glutathione (GSH) level drops. These changes become even more pronounced during cataractogenesis. In this report, the ability of AL-05712 and AL-05741 to lower PSSG and elevate GSH in three separate model systems was evaluated. AL-05741 was able to decrease PSSG in the cell-free system by over 30% at a concentration of 0.1 mM. AL-05712, the ester form of AL-05741, decreased mixed disulfides by about 8% in the same system in the absence of any cellular esterases. Both compounds could partially inhibit the loss of GSH seen in the H2O2 control in cultured rat lenses and in addition, the accumulation of PSSG was substantially decreased. Human lenses incubated in AL-05712 showed a significant elevation of cortical GSH and a decrease in PSSG in three of four sets of cultured human lenses.
authors.affiliation: W.C. Conner Research Center, Alcon Laboratories, Inc., Fort Worth, Texas 76134, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Dickerson
authors.forename: M
authors.initials: M
authors.lastname: Hellberg
authors.forename: M F
authors.initials: MF
authors.lastname: Lou
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001392:Azocines / Q000627:therapeutic use*; D002386:Cataract / Q000517:prevention & control*; D006801:Humans; D006834:Hydrazines / Q000627:therapeutic use*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D066298:In Vitro Techniques; D007908:Lens, Crystalline / Q000187:drug effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C116877:AL 05741; D000975:Antioxidants; D001392:Azocines; D006834:Hydrazines; C116878:N,N-dimethyl-N,N-bis((acetylthio)acetyl)hyrazine; D006861:Hydrogen Peroxide