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  • Title: Effects of 21-aminosteroids in neonatal rat cardiac myocyte cell cultures exposed to free radicals.
    Author: Burton KP.
    Journal: Cardiovasc Res; 1994 Oct; 28(10):1500-6. PubMed ID: 8001037.
    Abstract:
    OBJECTIVE: The aim was to test a group of 21-aminosteroids, U74006F, U75412E, and U74500E, known as lazaroids, for their ability to prevent alterations in neonatal rat cardiac myocytes exposed to solutions containing a xanthine oxidase mediated free radical generating system. METHODS: Myocytes were either left untreated (non-treated cultures) or pretreated for 15 min with the drug vehicle or one of the lazaroids. Myocytes were either examined as non-exposed control cultures or exposed to the free radical generating system for 60 min. Measurement of [3H]arachidonate label in a lipid extract of the culture medium and release of lactate dehydrogenase (LDH) into the medium were analysed. RESULTS: Myocytes not treated with lazaroids and vehicle treated myocytes exposed to free radicals showed a significant release of [3H]arachidonate and lactate dehydrogenase (LDH). At a dose 1 x 10(-5) M, all lazaroid treated myocytes showed significantly lower release of [3H]arachidonate measured in the total lipid extract compared to the non-treated or vehicle treated cultures. Release of [3H]arachidonate was significantly lower for the myocytes treated with U74006F and U74500E at 1 x 10(-6) M concentration. Only the U74006F treated myocytes showed protection at 1 x 10(7) M. LDH release was significantly attenuated at a dose of 1 x 10(-5) M for the U75412E treated myocytes and at 1 x 10(-5) and 1 x 10(-6) M for the U74500E treated myocytes compared to the myocytes not pretreated with a lazaroid and exposed to free radicals. CONCLUSIONS: Lazaroids provide protection against the release of [3H]arachidonate and LDH from myocardial cells exposed to free radical mediated injury. U74006F appeared to have the higher efficacy, at equal molar concentrations, in protecting against the release of [3H]arachidonate, whereas U74500E was observed to have the higher potency in inhibiting LDH release.
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