4-hydroxy-2-nonenal and sodium-bisulfide

4-HNE (4-hydroxy-2-nonenal) is a highly reactive α,β-unsaturated aldehyde generated from oxidation of polyunsaturated fatty acids and has been suggested to play a role in the pathogenesis of several diseases. 4-HNE can bind to amino acids, proteins, polynucleotides, and lipids and exert cytotoxicity. 4-HNE forms adducts (Michael adducts) with cysteine, lysine, as well as histidine on proteins with the thiol function as the most reactive nucleophilic moiety. Thus, detoxification strategies by 4-HNE scavenging compounds might be of interest. Recently, hydrogen sulfide (H2S) has been identified as an endogenous vascular gasotransmitter and neuromodulator. Assuming that the low-molecular thiol H2S may react with 4-HNE, methods to monitor the ability of H2S to counteract the protein-modifying and cytotoxic activity of 4-HNE are described in this chapter.

Topics: Aldehydes; Cell Line, Tumor; Cell Survival; Electrophoresis, Polyacrylamide Gel; Fatty Acids, Unsaturated; Humans; Hydrogen Sulfide; Hydrogen-Ion Concentration; Hydroxy Acids; Immunoblotting; Neurons; Oxidation-Reduction; Serum Albumin; Sulfhydryl Compounds; Sulfides

Although hydrogen sulfide (H2S) is generally thought to be a toxic gas, it has been reported to protect various tissues against ischemia-reperfusion injury. In the present study, we histologically investigated whether H2S, using sodium hydrosulfide (NaHS) as its donor, had a protective effect on N-methyl-d-aspartate (NMDA)-induced retinal injury in the rat in vivo. Under ketamine/xylazine anesthesia, male Sprague-Dawley rats were subjected to intravitreal NMDA injection. NaHS (0.163-120 μmol/kg) was intraperitoneally administered 15 min before NMDA injection. Morphometric evaluation at 7 days after NMDA injection showed that intravitreal NMDA injection resulted in ganglion cell loss. NaHS dose-dependently prevented this damage. NaHS (120 μmol/kg) significantly decreased the numbers of TUNEL-positive, 4-hydroxy-2-nonenal-positive, and 8-OHdG-positive cells 12 h after NMDA injection. In another experimental series, we demonstrated that NaHS (120 μmol/kg) significantly reduced the retinal injury induced by intravitreal NOC12 (400 nmol/eye), which was a nitric oxide donor and reported to induce oxidative stress, in the retina, 7 days after intravitreal injection. These results suggested that H2S protects retinal neurons against the injury induced by intravitreal NMDA in rats in vivo. Anti-oxidative activity of H2S are possibly involved in underlying protective mechanisms.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aldehydes; Animals; Antioxidants; Apoptosis; Cell Survival; Deoxyguanosine; Dose-Response Relationship, Drug; Excitatory Amino Acid Agonists; Hydrogen Sulfide; In Situ Nick-End Labeling; Injections, Intraperitoneal; Intravitreal Injections; Male; N-Methylaspartate; Nitric Oxide Donors; Oxidative Stress; Rats; Rats, Sprague-Dawley; Retinal Degeneration; Retinal Ganglion Cells; Sulfides