| Project/Area Number |
11671625
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Kochi Medical School |
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Principal Investigator |
OKATANI Yuji Kochi Medical School, Associate professor, 医学部, 助教授 (70145142)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | melatonin / pregnancy / free radical / oxidized LDL / homocysteine / preeclampsia / fetal distress / 妊娠 / nitric oxide |
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| Research Abstract |
1. We evaluated pathophysiologic role of melatonin in pregnancy as related to its antioxidant property. Production of melatonin in the pineal gland increased from second to third trimester of gestation.
This increase in melatonin synthesis may be attributable to the paralleling increase in the activity of Hidroxyindole-O-methyltransferase (HIOMT). Exogenous progesterone stimulated HIOMT activity in the pineal gland.
2. Oxidized LDL or homocysteine increased vascular tone and augmented the contractile response to serotonin in the human umbilical artery in ex vivo condition, perhaps by suppressing the endothelial synthesis of nitric oxide as well as by increasing calcium influx in the vascular smooth muscle cells. Pretreatment with melatonin significantly suppressed this vasospastic action. This protective effect of melatonin is probably mediated by scavenging oxygen free radicals arising from Oxidized LDL or from homocysteine autooxidation.
3. Melatonin administration to the mother rat increased antioxidant enzyme activities such as glutathione peroxidase and superoxide dismutase in fetal brain and placenta. These effects may thereby provide further protection against free radical injury.
4. Bilateral occlusion of the utero-ovarian artery and subsequent reperfusion in pregnant rats resulted in oxidative lipid and DNA damage in fetal rat brain. This ischemia and reperfusion impaired mitochondrial function in fetal rat brain and placenta.
Melatonin administration to the pregnant rat prevented the free radical-induced oxidative mitochondrial damage to fetal rat brain and placenta by a direct antioxidant effect and the activation of antioxidant enzymes.
Thus, because of this unique combination of actions, melatonin may show therapeutic promise in Oxidized LDL-, hyperhomocysteinemia-induced cardiovascular disease, such as preeclampsia and fetal distress, where free radical production has been implicated.
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