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Antioxidant mechanisms of ascorbate ...

Suh, Jung Hyuk.

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Antioxidant mechanisms of ascorbate and (R)-alpha-lipoic acid in aging and transition metal ion-mediated oxidative stress.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Antioxidant mechanisms of ascorbate and (R)-alpha-lipoic acid in aging and transition metal ion-mediated oxidative stress./
作者:	Suh, Jung Hyuk.
面頁冊數:	198 p.
附註:	Source: Dissertation Abstracts International, Volume: 64-12, Section: B, page: 6078.
Contained By:	Dissertation Abstracts International64-12B.
標題:	Chemistry, Biochemistry. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3116163
ISBN:	0496635996

Antioxidant mechanisms of ascorbate and (R)-alpha-lipoic acid in aging and transition metal ion-mediated oxidative stress.
Suh, Jung Hyuk.

Antioxidant mechanisms of ascorbate and (R)-alpha-lipoic acid in aging and transition metal ion-mediated oxidative stress. - 198 p.

Source: Dissertation Abstracts International, Volume: 64-12, Section: B, page: 6078.

Thesis (Ph.D.)--Oregon State University, 2004.

Oxidative stress is the major driving force behind the aging process and many age-related diseases. However, direct experimental evidence of whether antioxidants, such as ascorbate (AA) and lipoic acid (LA) can slow the progression of aging process and/or reduce risks of developing degenerative disease is largely absent. This suggests a better understanding of the precise mechanism of how dietary micronutrient affect parameters of involved in cellular redox balance and aging are warranted. In this dissertation, young and old rats were used as our model to understand potential pro-oxidant events that contribute to increases in oxidative stress in various tissues and how antioxidants such as ascorbate and lipoic acid influence these events. Our major findings are that the age-related impairment of mitochondria and increased deposition of iron contribute significantly to heighten levels of oxidative stress, as evidenced by the resultant increases in the rates of oxidant appearance and in the levels of oxidative damage to DNA, lipids and proteins. We find that AA and LA strongly protected against transition metal-ion dependent increases in oxidative stress. AA effectively inhibited transition metal-mediated lipide peroxidation in human plasma. LA in its reduced form effectively binds iron and copper in a redox inactive manner and reversed chronically elevated levels of iron in the brain without removing enzyme bound transition metal ions. LA also significantly attenuated the age-related increase in oxidative stress associated with mitochondrial decay in the heart, as evidenced by the improvements in AA levels and glutathione redox status. The declines in tissue GSH levels in aged rats were strongly associated with the diminished gamma-GCL activity (in parallel with decreased expression of the catalytic and modulatory subunits), and lowered Nrf2 expression and binding to ARE sequence in rat liver. Remarkably, all these events were effectively reversed by the administration of LA, modulating the parameters to return to the observed in young animals. The implications of this work open new avenues not only for further understanding of the aging process but also for possible strategies in its modulation by the micronutrients.

ISBN: 0496635996Subjects--Topical Terms:

1017722
Chemistry, Biochemistry.

Antioxidant mechanisms of ascorbate and (R)-alpha-lipoic acid in aging and transition metal ion-mediated oxidative stress.
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