Reduction of pantethine in rabbit ocular lens homogenate.
In several animal models, preliminary studies have indicated that pantethine may inhibit cataract formation. Therefore, preclinical trials need to be conducted to study the pharmacology of pantethine in the ocular lens and to establish its efficacy. Since pantethine, which is a disulfide, can undergo a variety of chemical modifications such as reduction and formation of mixed disulfides, a detailed study was first conducted to determine the stability of pantethine in rabbit lens homogenate. A knowledge of the stability of pantethine in lens homogenate was necessary to establish if pantethine could be metabolized in the time it takes to harvest and homogenize a lens. The results of this study will be used to establish a protocol for harvesting and homogenizing lens samples. Pantethine (100 microM) is completely reduced to pantetheine in rabbit lens homogenate in about 16 min. About 1.5% of the pantethine added to lens homogenate forms a mixed disulfide with lens proteins, and the remainder is found in the supernatant. The supernatant pantethine concentration decreases exponentially as a function of time, and the terminal half-life for this process is 3.3 min. The free supernatant pantetheine concentration increases in pseudo first order manner as a function of time with a rate constant of 4.3 min. Pantethinase activity is not significant, because the free supernatant pantetheine concentration did not decrease. The exact mechanism of pantethine reduction in rabbit lens homogenate remains to be determined.
Fisher
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Oculon Corporation, Cambridge, MA, USA. dhfisher@aol.com
Szulc
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D000818:Animals; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D004563:Electrochemistry; D007908:Lens, Crystalline / Q000201:enzymology / Q000378:metabolism*; D010084:Oxidation-Reduction; D010204:Pantetheine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D011817:Rabbits
D010204:Pantetheine; C005425:pantethine