coelenterazine and Hemolysis

Coelenterazine and derivatives were initially considered in the scientific community for their (bio)luminescent properties. Now, another interest of such hetero-bicycles has been pointed out by the discovery of remarkable antioxidative properties, and an unique mode of action as a "cascade": the mother-compound (imidazolopyrazinone) is transformed by ROS into a daughter-compound (2-amino-pyrazine) also endowed with antioxidative properties. This review illustrates the therapeutic potential of synthetic imidazolopyrazinones (coelenterazine analogues): chemical reactivity assays with singulet oxygen, radical anion superoxide, peroxynitrite, and radicals formed during lipid and LDL peroxidation, cellular tests of protection against oxidative stress using keratinocyte, hepatocyte, neuronal and erythrocyte cells, and finally in vivo evaluation in a hamster model of ischemia-reperfusion, are fully described.

Topics: Animals; Antioxidants; Drug Design; Hemolysis; Humans; Imidazoles; Lipid Peroxidation; Neuroprotective Agents; Oxidation-Reduction; Oxidative Stress; Peroxynitrous Acid; Pyrazines; Radiation-Protective Agents; Reactive Oxygen Species; Superoxides

European seabass (Dicentrarchus labrax) erythrocytes treated with tert-butyl hydroperoxide (t-BHP) showed decreasing levels of reduced glutathione, increased lipid peroxidation and DNA damage, and ultimately underwent haemolysis. The addition of the marine luciferin coelenterazine (CLZn) markedly delayed the onset of the haemolytic process induced by t-BHP as well as lipid peroxidation and glutathione oxidation. CLZn also protected the red blood cells' DNA against t-BHP-triggered damage. CLZn's oxidation product coelenteramine (CLM) also delayed the lysis of the cells as well as the occurrence of oxidative stress indicators but it did not offer protection against DNA damage. Both compounds proved more efficient than the vitamin E analogue Trolox C at similar doses. These results demonstrate the ability of CLZn and CLM to protect fish cells against oxidative stress, providing further support to the evolutionary model suggesting that CLZn's first physiological role was that of an antioxidant in fish thriving in surface layers of the ocean, later evolving into its light-emitting function in deep-sea species.

Topics: Animals; Bass; Chromans; Comet Assay; DNA Damage; Dose-Response Relationship, Drug; Erythrocytes; Glutathione; Hemolysis; Imidazoles; Lipid Peroxidation; Oxidative Stress; Pyrazines; tert-Butylhydroperoxide; Thiobarbituric Acid Reactive Substances