Inhibition of microsomal lipid peroxidation by naphthoquinones: structure-activity relationships and possible mechanisms of action |
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| Authors: | R E Talcott M T Smith D D Giannini |
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| Affiliation: | 1. Brain Tumor Research Center, Departments of Laboratory Medicine and Neurological Surgery, University of California, San Francisco, California 94143 U.S.A.;2. School of Public Health, University of California, Berkeley, California 94720 U.S.A.;3. Department of Pharmaceutical Chemistry, University of California, San Francisco, California 94143 U.S.A.;1. Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran;2. Students'' Scientific Research Center (SSRC), Tehran University of Medical Sciences (TUMS), Tehran, Iran;3. Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran;4. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran;5. Obesity and Eating Habits Research Center, Endocrinology and Metabolism Molecular–Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran;6. Food Security Research Center, Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran;1. Department of Endocrinology, Affiliated Hospital of Guilin Medical University, Guilin 541001, China;2. Department of Endocrinology, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou 545005, China;3. Department of Neurology, Affiliated Hospital of Guilin Medical University, Guilin 541001, China |
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| Abstract: | Menadione (2-methyl-1,4-naphthoquinone) is a remarkably potent inhibitor of microsomal lipid peroxidation, effective at submicromolar concentrations. Its possible mechanism of action and the relationship between naphthoquinone structure and antioxidant activity were the topics of this investigation. In the microsomal lipid-peroxidizing system dependent on NADPH and ferric pyrophosphate, menadione, at concentrations of 50 microM or higher virtually eliminated the accumulation of malondialdehyde and lipid hydroperoxides. In the NADPH-independent, cumene hydroperoxide-dependent system, menadione was also an effective antioxidant, but only in the presence of reducing equivalents. These and other observations indicate that a reduced form of menadione, either the hydroquinone or semiquinone, is the active antioxidant, and suggest that it may trap hydroperoxy radicals, alkoxy radicals, or other free radicals involved in propagating lipid peroxidation. Moreover, these results show that electron diversion per se cannot account for the antioxidant effects of menadione. A comparison of the antioxidant activities of eight 1,4-naphthoquinones indicated that methyl substitution of C-2, lack of steric hindrance at C-3 or C-5, and (in the case of weak acids) a relatively high pKa are favorable structural features associated with strong antioxidant activity. |
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