Date of Award

5-2002

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Environmental Science

First Advisor

Dr. R. Padmanabhan

Second Advisor

Dr. Ashok Kakadeekar

Third Advisor

Prof. Riad Bayoumi

Abstract

Background:

The risk of congenital anomalies in children of diabetic mothers is three to four times that in offspring of non-diabetic mothers. The exact mechanisms of these birth defects are not known. Of the several factors suggested to contribute to embryonic maldevelopment in diabetic pregnancy, the formation of reactive oxygen species (ROS) and subsequent disturbances to cellar defenses appears to be a plausible hypothesis. Antioxidants have been reported to rescue the embryos from being malformed in animal experiments. This study was aimed to determine if the ideal antioxidant lipoic acid would ameliorate the embryos from maternal diabetes-induced anomalies.

Methods:

Female Wistar rats (200-250 gm) were assigned to five different treatment groups. Non-treated control rats, streptozotocin (STZ) (60 mg/kg)-induced diabetes mellitus, STZ diabetic rats treated with lipoic acid (STZ+LA), lipoic acid and Tris buffer treated rats (LA control), and Tris buffer alone treated rats. LA control and STZ+LA groups were treated with daily intraperitoneal injection of 20 mg/kg LA from GD 6 through GD 19. Morphological and skeletal malformations of the embryos were recorded.

Results:

Diabetic rats showed a significant incidence of resorption, growth retardation and malformation of fetuses. Lipoic acid and Tris buffer treatments showed no significant differences when compared with non-treated control data. Diabetic rats supplemented with lipoic acid had a significant decrease in fetal resorption/death, and improvement in fetal body weight. Lipoic also significantly reduced the incidence of various external and skeletal malformations in the diabetic group.

Conclusion:

Lipoic acid exerts a potent protective effect against diabetes-related resorption, intrauterine growth retardation and malformations. Prospective studies should aim at evaluating the exact mechanism by which LA acts to rescue embryos of growth retardation and malformations in this model.

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