1993 Fiscal Year Final Research Report Summary
Possible involvement of active oxygen species on the patients with homocystinuria and the infants with respiratory distress syndrome
| Project/Area Number |
03670513
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pediatrics
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| Research Institution | Osaka Medical College |
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Principal Investigator |
OGIHARA Tohru Osaka Medical College Department of Pediatrics Assistant, 医学部, 助手 (00211128)
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| Co-Investigator(Kenkyū-buntansha) |
YASUDA Hiroshi University of Tokyo Department of Reaction Chemistry Assistant, 工学部, 助手 (10220154)
MINO Makoto Osaka Medical College Department of Pediatrics Professor, 医学部, 教授 (70090206)
KITAGAWA Makoto Osaka Medical College Department of Pediatrics Lecturer, 医学部, 助手 (70175298)
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| Project Period (FY) |
1991 – 1993
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| Keywords | Homocystinuria / LDL / Active Oxygen Species / Free Radical / Lipid Peroxidation / Allantoin / Uric Acid / Respiratory Distress Syndrome |
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| Research Abstract |
1).Homocystinuria : Homocystinuria is an inborn error of methionine metabolism that is characterized by the premature development of arteriosclerosis. As one of the major factors in the pathogenesis of arteriosclerosis, modification of low-density lipoprotein (LDL) has received widespread attention by many investigators. In this study, to elucidate the relationship between elevated homocysteine levels and premature arteriosclerosis, we investigated the role of homocysteine in the iron-catalyzed oxidative modification of LDL.When we incubated homocysteine with ferric iron, the content of sulfhydryl groups gradually decreased, and both superoxide and ferrous ion formed gradually. In this reaction thiobarbituric acid-reactive substances (TBARS) and fluorescent substances were formed, and the fragmentation of apoprotein B(apo-B) occured. The extent of oxidative modification was dependent on the concentration of homocysteine. Modification of LDL was suppressed until alpha-tocopherol consump
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tion reached a critical level. When the alpha-tocopherol content of LDL was increased 2.6 fold, both the formation of TBARS and the fragmentation of apo-B were suppressed to some extent. These results suggest that homocysteine might promote iron-catalyzed oxidation of LDL, and endogenous alpha-tocopherol can protect LDL against oxidative modification.
2).Respiratory distress syndrome : We measured plasma allantion concentration as a proposal marker for free radical generation in 11 premature infants with respiratory distress syndrome (RDS) and 11 without RDS (non-RDS). Plasma allantoin level in RDS infants between 3 and 12 hours of life was significantly higher than that in non-RDS infants, although no significant difference was found in two groups within 3 hours after birth. These observation suggests that some oxidants are acturelly generated in the aqueous phase of plasma in RDS infants and the measurement of allantoin may be a useful indicator for free radical involvement in neonates. Less
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