Meira Fields

Accumulation of sorbitol in copper deficiency: Dependency on gender and type of dietary carbohydrate

The present study was designed to examine tissue sorbitol levels in copper-deficient rats consuming dietary fructose as the only source of carbohydrate and to determine if any changes in tissue sorbitol levels are influenced by the sex of the rat. Tissue levels of glucose, sorbitol, fructose, and glyceraldehyde were measured along with the activities of aldose reductase and sorbitol dehydrogenase of male and female rats consuming copper-deficient or adequate diets containing either fructose or starch for 3 weeks. Regardless of copper status, sorbitol accumulated in the livers of males consuming fructose compared to females and to males eating starch. The greatest sorbitol accumulation in the kidney occurred in the copper-deficient male rat consuming the fructose diet. These results strongly suggest that the pathology and complications of copper deficiency in the male rat fed fructose may be due to the increased sorbitol contents of tissues.

No antioxidant effect of combined HRT on LDL oxidizability and oxidative stress biomarkers in treated post-menopausal women.

Objective: To compare oxidative stress and LDL oxidizability in postmenopausal women with and without HRT. Methods: In a cross sectional study, two groups of women, with or without combined per os HRT (1.5–2 mg estrogen associated with 10 mg dydrogesteron), were age and duration of menopause matched. Women were recruited after medical examination at LBSO (Oxidative Stress Laboratory), Joseph Fourier University, Grenoble, and Department of Gynecology, Grenoble University Hospital, France. Main outcome measures included determination of lipid profile and oxidative stress biomarkers (TBARS, LDL oxidizability, auto-antibodies against oxidized-LDL). Measurement of circulating levels of vitamin C, E, β-carotene, lycopene and total antioxidant plasma capacity. Results: HRT led to decreased plasma total and LDL cholesterol (p < 0.05), but did not affect oxidizability and oxidation of LDL. Circulating levels of antioxidant vitamins (β-carotene, vitamin C, vitamin E/triglycerides) and total antioxidant capacity of plasma and lipid peroxidation, assessed by plasma TBARs, were not different from controls in postmenopausal women receiving HRT. Conclusion: This study suggests that even if combined HRT modifies the blood lipid profile, it does not appear to influence oxidative status.

Alcohol consumption aggravates copper deficiency

Male weanling Sprague-Dawley rats were fed a copper-deficient (0.6 microgram Cu/g) diet containing either fructose or starch. Half of the animals fed the starch diet drank a 20% solution of ethanol in water. Ethanol was chosen as an agent to mimic fructose metabolism with the intention that ethanol will exacerbate the signs of copper deficiency and will negate the protective effect of dietary starch. The consumption of a 20% ethanol drink for 6 weeks by copper-deficient rats fed starch resulted in the exacerbation of the deficiency similar to that exerted by fructose. The signs associated with the deficiency in both alcohol and fructose consumption included anemia, heart hypertrophy with gross abnormalities, and mortality. In contrast, none of the copper-deficient control rats that drank water exhibited anemia or heart abnormalities, and none died of the deficiency. In addition, sorbitol pathway in the kidney and liver was stimulated by the consumption of alcohol and fructose. The data support the contention that the combination of certain metabolic pathways of carbohydrate metabolism with copper deficiency are responsible for the exacerbation of the deficiency.

Hepatic iron overload may contribute to hypertriglyceridemia and hypercholesterolemia in copper-deficient rats

The present study was conducted in order to determine whether hepatic iron retention in rats fed a copper-deficient diet containing fructose is associated with hypertriglyceridemia and hypercholesterolemia, and whether a reduction of iron intake will prevent elevation of blood triglycerides and cholesterol. Rats were fed from weaning either a copper-deficient (0.6 microgram Cu/g) or copper-adequate (6.0 micrograms Cu/g) diet for 4 weeks. Half the rats consumed either an adequate level of iron (50 micrograms Fe/g) or a low level (17 micrograms Fe/g). Reduction of iron intake reduced blood levels of both triglycerides and cholesterol in rats fed a copper-deficient diet containing fructose. In addition, hepatic lipid peroxidation was also decreased. The combination of high iron, low copper, and fructose may be responsible for increased levels of risk-factor metabolites associated with heart disease.

Effect of hepatic iron on hypercholesterolemia and hypertriacylglycerolemia in copper-deficient fructose-fed rats

The purpose of this investigation was to establish whether plasma cholesterol and triacylglycerol(s) in copper deficiency can be increased or decreased by hepatic iron levels. Weanling male Sprague-Dawley rats were randomly divided into six dietary groups based on levels of dietary copper and iron. They were fed from weaning their respective diets for 6 wk. Forty percent of the copper-deficient rats fed a 15.7 mumol Fe/g diet died; 22% of those fed a diet containing 8.6 mumol Fe/g died; and there were no deaths in the 3.4 mumol Fe/g diet group. Rats belonging to the group fed the high-iron diet also exhibited the highest levels of liver iron, liver glutathione, and plasma cholesterol and triacylglycerol(s) compared with those fed either the adequate or low levels of dietary iron. There was a direct correlation (r = 0.82 and 0.77, respectively) between levels of cholesterol and triacylglycerol(s) in plasma and hepatic iron concentrations. These results provide strong evidence that points to a major involvement of iron in the lipemia of copper deficiency. These data may be important to those individuals who consume large quantities of fortified iron foods and supplement with iron but whose intake of copper is suboptimal.

Impaired endocrine and exocrine pancreatic functions in copper-deficient rats: the effect of gender.

OBJECTIVE To examine the effect of gender on endocrine and exocrine pancreatic function in female and male rats fed from weaning a copper-deficient diet. METHODS Weanling male and female rats were fed a copper-deficient or adequate diet for 4 weeks. Rats were sacrificed after an overnight fast. Livers and pancreata were removed, weighed and the concentrations of copper and iron were determined. In addition, insulin was measured in pancreatic tissue and plasma. Lipase and amylase activities were measured in pancreas. Lipid peroxidation was assessed in liver. RESULTS Copper deficiency in the male resulted in a profound reduced glandular mass of the pancreas. The pancreas continued low activities of lipase and amylase but excessive levels of insulin. Iron retention in the pancreas of the copper-deficient male rat was greater than in the female counterpart. Effects of copper deficiency in female rats on pancreas mass and endocrine pancreas were of lesser magnitude compared with males. Plasma insulin in the female rat was much higher than in the male rat. Hepatic lipid peroxidation was increased by copper deficiency in the male rat but was unaffected in the female. CONCLUSIONS Data show that pancreatic atrophy is more pronounced in males compared with females, and the endocrine pancreas of the male is more susceptible to dietary copper deprivation than the female rat. The greater degree of pancreatic atrophy and associated abnormalities in males compared with females may be related to the greater retention of pancreatic iron and subsequent peroxidative damage.

Responses of insulin to oral glucose and fructose loads in marginally copper-deficient rats fed starch or fructose

The purpose of this study was to assess the effects of dietary fructose either alone or in combination with marginal copper deficiency in weanling male rats exposed to their respective diets for only 2 wk. This short duration of exposure to inadequate copper intake prevents progressive morbidity brought about by increasing periods of exposure to dietary copper deprivation. Weanling male rats were fed a copper-deficient (0.6 microgram Cu/g) or a copper-adequate (6.0 micrograms Cu/g) diet containing 62% fructose or 62% starch for 2 wk. Either an oral glucose or an oral fructose tolerance test was conducted after an overnight fast. Insulin levels were elevated by either oral glucose or oral fructose at fasting and at 30 min postload in rats fed fructose compared with those fed starch. Despite high levels of plasma, insulin blood glucose was not reduced. Marginal copper deficiency had no effect on either plasma insulin or blood glucose. Data identify fructose as the sole agent responsible for inducing adverse changes in glucose metabolism. Two weeks of fructose consumption was sufficient to produce these changes.

Level of dietary iron, not type of dietary fat, is hyperlipidemic in copper-deficient rats.

OBJECTIVE This study was conducted to determine whether high dietary iron will negate the protective effect of unsaturated fat against hyperlipidemia. METHODS Forty-eight weanling, male Sprague Dawley rats were randomly assigned to eight dietary groups differing in the levels of copper and iron and type of dietary fat (saturated or unsaturated). The diets were either deficient (0.6 microg Cu/g) or adequate (6.8 microg Cu/g) copper and either adequate (53 microg Fe/g) or high (506 microg Fe/g) iron. All diets contained starch as the sole source of dietary carbohydrate. RESULTS Regardless of the type of dietary fat, three copper-deficient rats fed the high levels of dietary iron died prematurely due to ruptured hearts. Surviving rats belonging to the copper deficiency and high-dietary iron regimen developed severe anemia, enlarged hearts and livers, and exhibited the highest levels of liver iron. These rats also developed hypercholesterolemia. Triglycerides were elevated by the consumption of high iron diets. CONCLUSION Data show that levels of dietary iron, not the type of dietary fat, are potential inducers of hypertriglyceridemia. Data also show that the combination of high iron intake and dietary copper deficiency is responsible for elevating blood cholesterol.

Antioxidant defense system in lung of male and female rats: Interactions with alcohol, copper, and type of dietary carbohydrate☆☆☆

Male and female rats were used to investigate the effects of type of dietary carbohydrate (CHO), copper, and ethanol consumption on lung antioxidant enzyme activities and levels of phosphorylated compounds in whole blood. Copper-deficient female rats exhibited a greater degree of copper deficiency than males, as assessed by hepatic copper concentration and hepatic copper superoxide dismutase (CuSOD) activity. However, copper-deficient male rats fed fructose-containing diets exhibited greater growth retardation, anemia, and heart hypertrophy than females consuming the same diets and males fed starch. In addition, one of 10 copper-deficient male rats that ate a fructose-based diet and drank water and one of 10 copper-deficient male rats that ate a starch-based diet and drank ethanol died. Copper-deficient, starch-fed males exhibited the highest activities of glutathione peroxidase (GSH-Px) and catalase as compared with fructose-fed rats. Ethanol consumption elevated the activities of GSH-Px and catalase. Copper-deficient female rats exhibited higher catalase but lower GSH-Px activities than males. It is suggested that in copper deficiency, the ability to increase antioxidant enzyme activities in rats consuming starch is greater than in rats consuming fructose. Rats fed starch are provided with a greater degree of protection against oxidative damage than rats fed fructose. In addition, polyphosphorylated compounds in blood were reduced in copper-deficient male rats that consumed fructose-based diets. This may impair supply of oxygen to tissues.

Antioxidant defense mechanisms in the female rat: interactions with alcohol, copper, and type of dietary carbohydrate

The purpose of this study was to examine the effects of ethanol, type of dietary carbohydrate (fructose vs. starch), and levels of dietary copper (deficient vs. adequate) on antioxidant defense mechanism in the female rat. The consumption of 20% ethanol in the drinking water depressed growth rate due to a reduction of feed efficiency. Ethanol also lowered hepatic copper concentration, but had no effect on hepatic iron. Among the three antioxidant enzymes studied [i.e., superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase], only catalase activity was increased by ethanol. This effect was independent of copper or the type of dietary carbohydrate. As expected, copper deficiency dramatically reduced SOD. Copper deficiency also reduced GSH-Px activity; however, the combination of fructose feeding with copper deficiency caused a further reduction in GSH-Px. The data show that copper deficiency, per se, and the combination of copper deficiency with fructose feeding lower the antioxidant defense system in female rats.