Allopurinol, an inhibitor of xanthine oxidase, reduces uric acid levels and modifies the signs associated with copper deficiency in rats fed fructose.

This study was designed to focus on the potential stress that xanthine oxidase could produce in copper-deficient rats fed fructose. Fructose consumption results in an excess production of uric acid due to an increased degradation of nucleotides. The enzyme xanthine oxidase catalyzes the oxidation of both hypoxanthine and xanthine. During the oxidation process free radicals are generated, which in turn, induce lipid peroxidation and premature death. Allopurinol -- a competitive inhibitor of xanthine oxidase -- could alleviate the combined effects of fructose feeding and copper deficiency. Twenty-five male rats were fed for 4 weeks from weaning a copper-deficient or adequate diet containing fructose. Twelve rats were given a daily oral dose of 5 mg allopurinol/100 g b.wt. Two copper-deficient rats that were not treated with allopurinol died prematurely during the fourth week of the study. No mortality occurred in the group of copper-deficient rats that had been treated with allopurinol. Anemia was alleviated by allopurinol, which in turn, could be responsible for improved growth rate. Allopurinol was effective in inhibiting xanthine oxidase activity in vivo as measured by the dramatic reduction of uric acid production. Lipid peroxidation, however, was not affected by allopurinol. It is concluded that the beneficial effects of allopurinol in copper deficiency do not appear to be related to prevention of oxygen radicals, but rather, to the protection against the catabolic destruction of purines, which in turn, increases nucleotide pool.

The influence of dietary carbohydrate and deferoxamine on developing copper deficiency of rats.

The present investigation was conducted to follow the development of copper deficiency in male rats from weaning (day 0) to day 31 of dietary copper deprivation and to correlate changes in tissue sizes with copper and iron concentrations. Male rats were fed for 31 days from weaning copper-deficient or adequate diets containing fructose or starch. Another copper-deficient group of rats that was fed fructose was treated with deferoxamine. Rats were killed at day 0, 8, 16, 24, and 31 of the study. In general, no correlation could be found between the development of heart hypertrophy, pancreatic and thymic atrophy, and tissue copper concentrations in copper-deficient rats fed fructose. In contrast, in the heart and pancreas a negative correlation existed between tissue size and iron concentration. In addition, anemia preceded heart hypertrophy. Deferoxamine lowered hepatic iron concentrations, ameliorated the anemia, and decreased heart size compared with untreated rats. The data of the present study suggest that tissue atrophy and hypertrophy and the severity of copper deficiency are not solely due to tissue concentrations of iron and/or copper.

Anemia plays a major role in myocardial hypertrophy of copper deficiency.

The present study was undertaken to establish whether anemia plays a role in the cardiomegaly and myocardial pathology of copper deficiency. Fifteen weanling male rats were fed a copper-deficient (0.6 microgram Cu/g) diet for 5 weeks. Six rats were intraperitoneally injected once a week with packed red blood cells (RBC) that were obtained from copper-deficient rats fed starch. The remainder (n = 9) served as controls. The administration of RBC to copper-deficient rats fed fructose prevented the anemia. As a result, none of the injected rats exhibited heart hypertrophy or gross pathology and they all survived. In contrast, all other control, nontreated copper-deficient rats that were fed fructose were anemic and all exhibited severe signs of copper deficiency, which included heart hypertrophy with gross pathology, and four died of the deficiency. The data suggest that the anemia of copper deficiency contributes to heart pathology. Once the anemia is prevented, the copper-deficient rats should be protected against heart pathology and mortality.

The role of the adrenals in copper deficiency.

The present study was undertaken in order to establish whether (1) a decrease in catecholamines will prevent the heart hypertrophy of copper deficient rats fed fructose, and (2) an increase in hepatic copper concentration will ameliorate the signs associated with copper deficiency when fructose-based diets are consumed. Adrenalectomy resulted in reduced plasma glucocorticoids and a threefold increase in hepatic copper concentration. The signs associated with the deficiency were not ameliorated in rats fed fructose. In addition, the reduction in catecholamine concentration did not protect the copper-deficient rats fed fructose against cardiomegaly and mortality. The data support the contention that the severity of copper deficiency in rats fed fructose is not solely dependent on hepatic copper concentration and/or levels of catecholamines.

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.

The influence of gender on developing copper deficiency and on free radical generation of rats fed a fructose diet.

The present investigation was conducted to determine whether differences in copper and iron status between male and female rats can be detected during the development of copper deficiency. These differences may explain the protection of the female against the severity of copper deficiency. In addition, the livers of all rats were exposed to electron-spin resonance (ESR) spectroscopy for the presence of free radicals. Male and female rats were fed from weaning either copper-deficient or -adequate diets containing fructose for 31 days. Rats were killed at day 0, 8, 16, 24, and 31 of the study. Throughout the study, copper-deficient males exhibited the same organ copper concentrations as copper-deficient female rats. However, only in the male did copper deficiency cause a reduction in body weight and an increase in liver and heart sizes but a decrease in pancreas size. In contrast, organ iron concentrations were different between males and females. Only copper-deficient males were anemic. Only the livers of copper-deficient males showed the presence of free radicals. Although the livers of copper-deficient female rats exhibited higher concentrations of hepatic iron than their male counterparts, their livers did not show the presence of free radicals. The data of the present study suggest that changes in organ sizes and the severity of copper deficiency are not solely due to the total concentrations of iron and/or copper. The type of iron compound and the presence of free radicals may be involved in the pathology of copper deficiency of the male.

The severity of copper deficiency can be ameliorated by deferoxamine.

The present study was undertaken in order to determine whether hepatic iron overload plays a role in the exacerbation of copper deficiency. Weanling male Sprague-Dawley rats were fed a copper-deficient (0.6 microgram Cu/g) diet containing 62% fructose for 5 weeks. Some of the copper-deficient rats were injected daily with deferoxamine (DFX), an iron chelator that has been widely used to reduce iron overload. DFX reduced hepatic iron concentrations, which in turn ameliorated the pathology of copper deficiency when compared with nontreated copper-deficient animals. It is suggested that hepatic iron overload in a reduced environment plays a major role in the exacerbation of copper deficiency. Once the concentration of hepatic iron is reduced, the severity of the deficiency should be improved.

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.

Alcohol consumption mimics the effects of a high-fructose, low-copper diet in rats.

The consumption of a high-fructose diet that is inadequate in copper produces numerous pathologies which eventually lead to the mortality of the animals. In contrast, the consumption of a high-starch diet that is inadequate in copper does not produce abnormalities and the animals survive. Ethanol has been chosen as an agent to mimic the fructose effect in copper deficiency. The administration of 20% ethanol in the drinking water of rats fed a starch-based diet that was inadequate in copper resulted in a depressed growth rate, anemia, pancreatic atrophy, and heart hypertrophy. All these signs were similar to the signs exerted by fructose feeding when it was combined with copper deficiency. Polyol pathway in the liver and kidney was affected by both ethanol and fructose consumption. Ethanol did not aggravate the signs associated with copper deficiency in rats fed fructose, but it exacerbated the signs associated with copper deficiency in rats fed starch. Certain metabolic pathways that are unique for fructose and ethanol may be responsible for the exacerbation of copper deficiency.

Antioxidant defense mechanisms in the male rat: interaction with alcohol, copper, and type of dietary carbohydrate.

The activities of enzymes participating in cellular protection against free radical reactions were measured in hepatic tissues from copper-adequate and copper-deficient rats fed fructose or starch-based diets. Half of the rats consumed 20% ethanol in their drinking water. The consumption of ethanol depressed growth rate, reduced hematocrit, and hepatic copper concentration. Feed efficiency was greatly depressed by ethanol. Mortality due to copper deficiency occurred in fructose-fed rats and in starch-fed rats that drank ethanol. Ethanol had no effect on superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), or catalase. In contrast, copper deficiency reduced SOD and fructose feeding depressed catalase activity. GSH-Px was not affected by either the type of dietary carbohydrate, copper, or ethanol. Taken together, these data suggest that additional mechanisms to antioxidant defense systems are responsible for the metabolic changes that occur during the interactions between ethanol low copper and dietary carbohydrates.

Effect of coenzyme Q10 supplementation on cardiac hypertrophy of male rats consuming a high-fructose, low-copper diet.

Administration of coenzyme Q10 to humans and animals has a beneficial effect on a number of cardiac diseases. The purpose of the present study was to determine if coenzyme Q10 treatment could ameliorate cardiac abnormalities associated with the carbohydrate x copper interaction in rats. Weanling male rats were provided with a copper-deficient diet (0.6 microgram Cu/g) containing either 62.7% starch (S-Cu) or fructose (F-Cu) for 5 wk. Half of the rats provided with the F-Cu diet were given daily oral supplements of 300 mg coenzyme Q10/kg body weight (F-Cu + Q). Heart hypertrophy, liver enlargement, or pancreatic atrophy were not affected by, nor was body growth or anemia improved by, supplementation with coenzyme Q10 when compared to rats fed only the F-Cu diet. Hearts from rats fed the F-Cu diet had severe inflammation, degeneration, fibrosis, and giant mitochondria with abnormal cristae. Hearts from F-Cu + Q rats had similar mitochondrial changes as the F-Cu rat hearts but without any apparent degenerative changes. None of the F-Cu + Q rats, but 30% of the F-Cu rats, died during the study as a result of heart rupture. These observations show that whereas coenzyme Q10 treatment did not prevent the cardiac hypertrophy of the carbohydrate x copper interaction, it did play a role in maintaining the integrity of the heart.

Copper deficiency in rats: the effect of clofibrate.

This study was undertaken to determine whether hepatic lipogenesis plays a role in the exacerbation of copper (Cu) deficiency. Forty-eight male rats were fed from weaning a Cu-deficient or adequate diet containing 62% carbohydrate as either starch or fructose with or without clofibrate for 5 weeks. Clofibrate was fed since it had been shown to possess hypolipidemic properties. Administration of clofibrate reduced the activity of the lipogenic enzyme glucose-6-phosphate dehydrogenase. Total hepatic lipid, however, was not reduced. Clofibrate did not affect hepatic lipid concentration and the pathology associated with Cu deficiency when fructose was fed was not prevented by the consumption of clofibrate.

Cardiomyopathy of copper deficiency: effect of vitamin E supplementation.

The present study was undertaken to determine whether the intraperitoneal injection of vitamin E to copper-(Cu) deficient rats fed fructose will protect the animals against the severity of Cu deficiency. Cu-deficient and adequate rats were fed a diet containing 62% carbohydrate as fructose. Half the Cu-deficient rats fed fructose were injected daily with vitamin E. Vitamin E treated rats were not protected against the lethal consequences of the interaction between Cu and fructose. These data provide evidence that the cardiomyopathy of Cu deficiency in rats consuming a fructose-based diet cannot be ameliorated by vitamin E supplementation.

Garlic oil extract ameliorates the severity of copper deficiency.

This study was undertaken to determine whether a reduction in hepatic lipogenesis would be beneficial in the amelioration of copper (Cu) deficiency when fructose is fed. Garlic was chosen as the agent for reducing hepatic lipogenesis. Forty-eight weanling rats were fed Cu-deficient or adequate diets containing fructose or starch with or without garlic for 5 weeks. Garlic ameliorated the signs associated with Cu deficiency, although hepatic lipogenesis was not affected. Administration of garlic reduced the activity of the lipogenic enzyme glucose-6-phosphate dehydrogenase only in Cu-adequate rats. Consumption of garlic resulted in increased epididymal fat pad and pancrease sizes, and higher hematocrits, insulin and thyroxine concentrations. Mechanisms other than lipogenesis that could be responsible for this phenomenon are discussed.

Copper deficiency in rats: the effect of type of dietary protein.

The present investigation was conducted to determine whether type of dietary protein can exacerbate the pathology induced by the combination of fructose feeding and copper (Cu) deficiency. Weanling male Sprague-Dawley rats were assigned to three different groups differing in the nature of dietary protein. The proteins used were egg-white, casein or lactalbumin. All diets contained 62.5% carbohydrate as fructose and were low in Cu (0.6-0.72 microgram Cu/g diet). Although the lowest concentration of Cu was found in the livers of rats fed egg-white, the pathology associated with Cu deficiency was more severe in rats fed lactalbumin. The highest concentration of hepatic Cu was found in rats fed casein. The data show that the type of dietary protein can exacerbate signs associated with Cu deficiency. The concentrations of hepatic Cu do not reflect accurately the pathology associated with Cu deficiency.

Dietary ferric vs. ferrous iron in copper-deficient rats fed fructose-based diets.

OBJECTIVE: This preliminary study was undertaken to determine whether the valence state of dietary iron affects signs associated with copper deficiency in rats fed fructose. METHODS: Rats were fed either copper-deficient or adequate diets containing 62% fructose as the sole dietary carbohydrate for 5 weeks. The mineral mixture contained equal concentration of either ferric or ferrous iron. RESULTS: Copper deficiency resulted in growth retardation, anemia, heart hypertrophy but pancreatic atrophy. The consumption of ferrous iron resulted in increased hematocrit and pancreas size. The combination of ferrous iron with copper deficiency reduced heart size. CONCLUSIONS: Copper deficiency had a major impact on each parameter measured. Although the valence state of iron did not protect the rats against the pathological consequence of copper deficiency it did have some positive effects. It may be that ferrous iron is a more available form than ferric iron.

Requirements for biotin are not affected by the combination of copper deficiency and fructose feeding.

OBJECTIVE: The objective of the present study was to establish whether copper (Cu)-deficient rats fed a diet containing fructose as their sole carbohydrate source require more biotin than the recommended 2 mg/kg diet when egg-white serves as the dietary protein. METHODS: Eighty weanling male Sprague-Dawley rats were randomly divided into 8 groups according to type of dietary carbohydrate (starch or fructose), level of Cu (0.6 micrograms Cu/g diet or 6.0 micrograms Cu/g diet) and level of biotin (2 mg/kg diet or 10 mg/kg diet). RESULTS: Regardless of the level of dietary biotin, Cu-deficient rats fed a fructose-containing diet exhibited growth retardation, anemia, atrophied pancreata, enlarged hearts and similar death rates. The remaining Cu-deficient rats fed fructose were emaciated and sick regardless of dietary biotin levels. The concentration of biotin in serum and biotin content of liver of rats fed fructose were higher than corresponding values from rats fed starch. CONCLUSION: Cu-deficient rats fed fructose are not deficient in biotin compared to published normal values. Supplementation of 10 mg/biotin/kg diet did not improve morbidity or mortality and therefore was not beneficial.

Low dietary iron prevents free radical formation and heart pathology of copper-deficient rats fed fructose.

Two studies were conducted to determine whether hepatic iron overload in rats fed fructose plays a role in the exacerbation of the signs associated with copper deficiency. When fed the adequate iron diet (50 micrograms Fe/g), copper-deficient rats fed either fructose or starch exhibited hepatic iron overload of similar magnitude. However, only livers of copper-deficient rats fed fructose exhibited the presence of high peaks associated with an iron compound detected by electron spin resonance. In addition, only copper-deficient rats fed fructose developed anemia, pancreatic atrophy, and heart hypertrophy with histopathologic changes, and they died prematurely of heart-related abnormalities. Lowering dietary iron from 50 micrograms/g to 30 micrograms/g was not sufficient to protect the animals against the pathologic consequences of copper deficiency. In contrast, the consumption of a fructose diet inadequate in both copper (0.6 micrograms/g) and iron (17 micrograms/g) resulted in the reduction of hepatic iron, which in turn caused the amelioration of the deficiency, compared with rats fed the adequate iron (50 micrograms/g) diet. None of these rats developed pancreatic atrophy, none exhibited myocardial lesions, and none died of the deficiency. Electron spin resonance spectra of their livers did not show the presence of free radicals. The data suggest that hepatic iron overload plays a role in the exacerbation of copper deficiency only when fructose diets are consumed.

Factores de riesgo de la muerte fetal anteparto / Risk factors for antepartum fetal death

La muerte fetal supone más de la mitad de las muertes perinatales. El grupo con mayor morbimortalidad corresponde a los recién nacidos que asocian prematuridad y bajo peso. Hay una marcada tendencia a repetir el mal resultado de la gestación anterior. Se presentan 2 casos de muerte fetal, y se realiza una revisión de las causas más frecuentes y de su influencia. El estudio de las alteraciones maternas, fetales y placentarias puede, en algunos casos, establecer la etiología de la muerte fetal (AU)

Fetal death represents more than half of perinatal deaths. Morbidity is highest in newborns who associate prematurity and low birth weight. Adverse pregnancy outcomes show a marked tendency to be repeated. We present two cases of fetal death and review the most frequent causes of this adverse outcome and their influence. Study of maternal, fetal and placental alterations can sometimes establish the etiology of fetal death (AU)