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Description:
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Previous studies have shown that the composition of membrane phospholipids reflects the fatty acid composition of the diet . Membranes that contain a high proportion of polyunsaturated fatty acids (PUFA ) are potentially more susceptible to attack by free radicals . Radicals are reactive chemical species that contain one or more unpaired electrons . Oxygen and some of its metabolites are radicals that are highly reactive , potentially toxic to the cell , and have been implicated in a variety of disease processes . Double bonds within PUFA participate in reactions with these radicals and propagate their formation . Cells contain protective antioxidant mechanisms including superoxide dismutase (SOD ) , glutathione peroxidase (GSHPx ) , catalase (CAT ) , glutathione (GSH ) , glutathione reductase (GSSGRx ) , glutathione -S -transferase (GST ) among others . Cellular damage results as these mechanisms become depleted . The effects of dietary fat on these antioxidant mechanisms in colon mucosa were examined using male Sprague -Dawley rats . Animals were fed one of four AIN 76A -based test diets differing in amount and type of lipid . The basal diet (BD ) contained 5 % corn oil ; the menhaden oil diet (MO ) contained 1 % corn oil and 19 % menhaden oil ; the corn oil diet (CO ) contained 20 % corn oil ; and the beef tallow diet (BT ) contained 1 % corn oil and 19 % beef tallow ; all were adjusted to provide equal amounts of other nutrients . Homogenates of colon mucosa were assayed after 2 weeks , 1 , 3 , 6 and 9 months for activities of CAT , GSHPx , SOD , GST , GSSGRx , and total GSH content .
In the first objective of this study , measurements were made at the various time points in rats fed test diets to determine whether diets high in polyunsaturated fatty acids (PUFA ) would produce an increased demand on antioxidant activity in colon mucosa . Beginning at the 2 -week time point GSH , GSSGRx , and SOD showed differences due to diet . At 1 month only GST showed differences . Then , at the 3 -month point , GSH , GSSGRx , GSHPx , and at the 6 -month point , GST , SOD , GSHPx and CAT , respectively , were affected . By the 9 -month time point , only CAT showed differences due to diet . Both the type and amount of fat in the <ii - &t affected these antioxidant mechanisms . However , the greatest number of significant differences were seen between the low -fat and high -fat diets , with the low -fat diet generally showing greater antioxidant capability . None of the high -fat diets were consistently more protective with regard to antioxidant capability , and there were no detectable differences in antioxidant activity according to the polyunsaturated fatty acid composition of the diet . When compared to the high -fat diets , the BD group showed greater GSHPx activity at the 3 - and 6 -month time points , higher GSH concentration and GSSGRx activity at 2 weeks , and higher GST activity at 6 months . BD and MO -fed animals had higher levels of CAT and GSSGRx activity as compared to the CO and BT diets at various time points , while BT and CO -fed animals showed greater GST activity . The age of the animal also affected these parameters , as SOD , GSSGRx , and GSHPx activities , as well as GSH , decreased over time . Ornithine decarboxylase activity was not induced by the diets and malondialdehyde was virtually undetectable at any time point in any of the diets . Therefore , this tissue appeared capable of compensating for all of the changes in antioxidant activity resulting from dietary treatment alone .
In a second objective of this study , the colonic antioxidant response to 1 ,2 -dimethylhydrazine (DMH ) was determined . Again , rats were fed one of the test diets as used in the first objective and given one or two intraperitoneal injections of either DMH (20 mg /kg ) or an equal volume of 1 mmol /L EDTA . Colon homogenates were measured for antioxidant activity as in the first objective and nuclear aberrations were quantitated . DMH modulated antioxidant mechanisms in the colon primarily through increases in GSH content in all diets . EDTA treatment alone also caused unexplained changes in these mechanisms . (Diets high in PUFA did not consistently differ from diets high in saturated fatty acids in response to DMH . MnSOD , an enzyme found to have very low or absent activity in a wide variety of tumors and transformed cell lines , decreased in this study in all diets as the result of DMH treatment . Colon mucosal membranes were apparently resistant to peroxidation as malondialdehyde formation continued to be low after DMH challenge . The MO group showed the greatest lipid peroxidation , among the diets , while the CO group resulted in the greatest number of nuclear aberrations . The significance of lipid peroxidation and its relationship to carcinogenesis in this tissue remains uncertain .
The fatty acid composition of colon mucosal microsomes varied according to the fatty acid composition of the diet . Variation occurred primarily in the type of unsaturated fatty acids that became incorporated , with the MO -fed animals showing a higher content of long chain , unsaturated n -3 fatty acids and lower concentrations of linoleic and arachidonic acids . Linoleic acid concentration was highest in the CO group and monounsaturated fatty acid incorporation was highest in the BT group .
Results from both objectives of this study demonstrated that dietary fat intake influences antioxidant activity in the colon . The low -fat BD appeared to have some advantages over the high -fat diets regarding antioxidant protection . However , none of the high -fat diets appeared more protective and there were no detectable differences in antioxidant mechanisms according to PUFA content of the diet . Implications are that a high -fat intake , regardless of the source , may increase oxidative stress in the colon . |