The protective effect of phytic acid on reducing oxidative stress in β2-microglobulin deficient mice
Date
1999
Authors
Guo, Ling
Major Professor
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Reddy, Manju
Committee Member
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Abstract
The objectives of this study was to examine the effect of dietary fat-induced oxidative stress in genetic iron overload and the protective effect of phytic acid (PA) in reducing oxidative stress in [Beta]2-microglobulin deficient mice ([Beta]2m-/-), a model for human hemochromatosis' (HH). Sixty-four [Beta]2m-/- mice were randomly assigned to 3 treatments: control, atherogenic, and polyunsaturated fatty acid (PUFA) diets. One-half of the mice in each treatment were fed 2% (w/w) phytic acid. One group of [Beta]2m+/+ mice (wild type) was fed a control diet. All seven groups were fed for 10 weeks with 50 ppm iron containing diet (AIN-93G). Measured indices were free iron, cholesterol, and TG (TG) concentrations in the serum; nonheme iron, thiobarbituric acid-reactive substances (TBARS), superoxide dismutase (SOD), and catalase concentrations in the liver. Nonheme iron concentration in [Beta]2m-/- mice was not only 30-50 times higher in the liver than in the heart and in the kidney, but also 20 times higher (p<0.0001) than that in the wild-type mice. Compared to the wild-type mice, [Beta]2m-/- mice had a significantly higher concentration of free iron in the serum (p<0.000 1), 6-fold higher hepatic TBARs (p<0.0001) and 18% lower hepatic SOD level, Our results clearly suggest that increased free iron concentration is responsible in increasing oxidative stress in [Beta]2m-/- mice.Feeding an atherogenic diet to [Beta]2m-/- mice, liver nonheme iron concentration was significantly reduced (p<0.001) by 70%, but had no effect on the free ironconcentration.
A further increase (two to three-fold) in hepatic lipid peroxidation and a reduction (37%-50%, P<0.01) in the hepatic SOD levels were observed by feeding atherogenic and PUFA diets. When PA was added to the control diet, a reduction (26-50%) of iron concentration was seen in liver, heart, and kidney. The addition of PA also significantly reduced TBARs in all three dietary groups, but most effectively in the control group. An increase in SOD concentration was seen only in the PUFA group, but serum TG concentration was reduced in both dietary fat groups. In conclusion, our results suggest that PA protects against oxidative stress induced by genetic iron overload alone or together with high dietary fat.
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