The effects of coadministration of dietary copper and zinc supplements on atherosclerosis, antioxidant enzymes and indices of lipid peroxidation in the cholesterol-fed rabbit

It has previously been shown that dietary copper can modulate the extent of atherosclerosis in the thoracic aorta of cholesterol-fed rabbits. The metabolism of copper and zinc are closely related, and it has been hypothesized that the balance of dietary copper to zinc may be important in determining coronary risk. Hence, we have investigated the interaction between dietary copper and zinc in atherogenesis in the New Zealand White rabbit. Juvenile male rabbits were randomly allocated to eight groups. Four groups were fed a normal chow diet with zinc (0.5%, w/w), copper (0.2%, w/w), copper plus zinc or neither in their drinking water for 12 weeks. Four other groups were fed a diet containing 0.25-1% (w/w) cholesterol plus zinc, copper, both or neither. Serum cholesterol of individual animals was maintained at approximately 20 mmol/l. Integrated plasma cholesterol levels were similar for all groups receiving cholesterol and significantly higher than those in the chow-fed groups (P < 0.001). Aortic copper concentrations were higher in the animals receiving cholesterol diets with copper compared to rabbits receiving normal chow and copper (P < 0.001). Aortic zinc content was significantly higher in cholesterol-fed rabbits supplemented with zinc alone or with copper than in those fed cholesterol alone (P < 0.001). Plasma ceruloplasmin concentrations were significantly higher in groups receiving cholesterol, irrespective of their trace element supplementation (P < 0.001). However, trace element supplementation increased the level significantly (P < 0.05). Trace element supplements did not appear to affect erythrocyte superoxide dismutase in the cholesterol-fed animals; however, zinc supplementation was associated with a significant increase in the enzyme in chow-fed animals (P < 0.05). The activity of the enzyme per mg of protein in aortic tissue was higher in animals receiving copper in the presence of cholesterol (P < 0.05) but not significantly so in its absence. Dietary trace element supplementation in cholesterol-fed animals was associated with a significant reduction in aortic lesion area. Plasma thiobarbituric acid-reactive substances and FOX concentrations were both significantly higher in the cholesterol-fed rabbits compared with the animals that fed on a chow diet (P < 0.001), and these were reduced significantly by dietary copper or zinc supplementation (P < 0.001). Hence, dietary supplements of copper or zinc at the doses used both inhibited aortic atherogenesis in the cholesterol-fed rabbits, although there was no significant additional effect when given in combination.     

Dietary composition alters gentamicin-induced nephrotoxicity in rats

Previous studies have shown temporal variations in gentamicin-induced renal toxicity characterized by a peak when administered during the resting period and a trough during the active period. This time-dependent toxicity was also altered according to the macronutrient composition of dietary regimens offered to female rats. In the present study, adult female Sprague-Dawley rats were adapted to semipurified isocaloric diets containing 20% casein or soy-protein (10% fat each) or to a standard chow diet (18.1% mixed proteins; 4.5% fat). The animals were then chronically treated for 10 days with a nephrotoxic dose of gentamicin sulfate (40 mg/kg/day ip) or a saline solution administered in the middle of their resting period (1200 h) or in the middle of their activity period (0000 h). Body weights of rats injected in the middle of their resting period decreased over the last 6 days of gentamicin treatment. Total 12-h light and 12-h dark food intakes were decreased in gentamicin-treated rats. Rats fed the standard chow diet had significantly lower corticocellular regeneration, serum creatinine and blood urea nitrogen compared to those fed the casein- and soy-containing diets. The present study demonstrates that chronic gentamicin-induced renal toxicity varies temporally according to the time of administration and that a mixed protein diet containing a lower fat level can protect against gentamicin-induced nephrotoxicity.     

The ultrastructure of the intestinal epithelium in Oreochromis niloticus on a diet with different concentrations of zinc

The effects of diets with variable zinc levels on the midgut epithelial cells were studied in Oreochromis niloticus L. One hundred and twenty fry of tilapia were apportioned into 4 experimental groups (I, II, III and IV groups), with 30 fish in each treatment, 5 replicate aquaria per treatment containing 6 fish each. The animals of the 4 groups were fed with isonitrogenous (30% crude protein) and isoenergetic (3000 Kcal/Kg of digestible energy) diets with increasing quantities of zinc (44.59; 149.17; 309.93; 599.67 mg Zn/kg of diet), twice a day, for 93 days. Three fish from each group were sacrificed at 36, 66 and 93 days and samples of midgut were removed for ultrastructural analysis. After 93 days of treatment, 3 animals of each experimental group were used for the analysis of zinc concentration by atomic absorption spectrophotometry. The comparative relative index (CRI) revealed that the animals in groups II, III and IV contained, respectively, 1.99%, 34.67% and 22.78% more zinc than the mean concentration in animals from group I. The ultrastructural analysis showed enterocytes with swelling of smooth surfaced endoplasmic reticulum and dilated mitochondria with variable matrix rarefaction and cristae number reduction in the fish exposed to 599.67 mg Zn/Kg of diet at 66 and 93 days of treatment.     

Decreased absorption and retention rates of magnesium in the rats fed on spinach-supplemented diets: possible explanations.

We studied the bioavailability of magnesium (Mg) in spinach after boiling with distilled water, using Mg-deficient growing male rats. The rats were fed a semipurified diet (Mg:0.063 per cent (w/w)) for 3 days. then a Mg-deficient diet (Mg:0.001 per cent (w/w)) for 5 days. They were then divided randomly into 7 groups of 6 rats each, and fed the semipurified diet (Mg: 0.063, 0.045 or 0.027 per cent (w/w)), or the spinach-supplemented diet (10 per cent (w/w) dried and powdered spinach after boiling with distilled water for 3 min at 100 degrees C). The Mg content of the diets supplemented with spinach grown on chemical nutrients, and on manure from pigs, cattle and fowl, was 0.069, 0.051, 0.043 and 0.036 per cent (w/w), respectively. Water intake and volumes of urine and faeces were significantly greater in the rats fed the spinach-supplemented diets than in those fed the semipurified diets. Apparent absorption of Mg, and urinary and faecal excretions of Mg were directly related to Mg intake: no significant difference was observed amongst the groups. Both the ratios of Mg absorption and retention were significantly lower in the rats fed diets supplemented with spinach than in those fed semipurified diets. The plasma Mg level was directly related to Mg intake in the rats fed the semipurified diets and the spinach-supplemented diets. However, the plasma Mg level in the rats fed spinach grown organically on manure from fowl tended to be higher than in the other groups. From these results, it was concluded that bound Mg in spinach was effectively utilized by Mg-deficient rats, however, the absorption and retention rates of Mg in rats fed diets supplemented with spinach were decreased. Possible explanations were discussed.     

A Morphologic and Biochemical Study of Nutritional Nephrocalcinosis in Female Rats Fed Semipurified Diets

Nephrocalcinosis occurred in weanling female rats fed a semipurified diet for 8 weeks. Mineralization of the inner cortex began after 3 weeks on the semipurified diet, and was most severe after 8 weeks. Intraluminal calcification was observed first in the pars recta of the proximal convoluted tubule; calcification of cytoplasmic organelles or basement membranes of the tubular epithelium was not observed. At the end of 8 weeks, some mineral deposits were seen within Henle's loops of the outer medulla. Histochemical studies demonstrated that the deposits contained calcium and phosphorus and had a glycoprotein matrix; electron diffraction studies indicated that the main mineral phase was hydroxyapatite. No differences in serum calcium or phosphorus or in the ultrastructural characteristics of the thyroid parafollicular cells and the parathyroid parenchymal cells were observed between animals fed the semipurified diet and those fed a commercial chow. The urinary excretion of calcium and magnesium was less and urinary citrate excretion was greater in animals fed the semipurified diet.     

Action of metabolic hormones on the fine structure of liver cells. II. Effects of hypophysectomy and chronic administration of somatotropin

Electron microscopic studies of hepatocytes from sham-operated, hypophysectomized, and hypophysectomized rats treated with somatotropin were undertaken in order to obtain morphological information on the mechanism of hormone action at the cellular level. Fed and fasted animals from each of the above groups were studied. Hepatocytes from fed rats of the three groups showed similar characteristics: periportal cells contained large dense masses of glycogen throughout the cytosome with relatively little smooth endoplasmic reticulum; mid-lobular cells displayed small dense masses of glycogen with few associated elements of smooth endoplasmic reticulum; centrilobular hepatocytes showed dispersed glycogen and abundant smooth endoplasmic reticulum. Hepatocytes from hypophysectomized rats fasted fifteen hours showed significant alterations in structure when compared with liver cells from sham-operated animals. Differences noted were: decrease in mid-lobular cell size and amount of smooth endoplasmic reticulum; decrease in glycogen, number of ribosomes and polysomes per hepatocyte; disorganization of the rough endoplasmic reticulum; and swelling of mitochondria and increase in number per cytoplsmic volume. Periportal hepatocytes from fasted hypophysectomized rats treated with somatotropin for ten days contain numerous small masses of glycogen with elements of smooth endoplasmic reticulum at the periphery of the glycogen masses. Mid-lobular and centrilobular hepatocytes contain masses of dispersed glycogen with an abundance of smooth endoplasmic reticulum associated with the glycogen particles.     

Effects of a gastric implant on body weight and gastrointestinal hormones in cafeteria diet obese rats

In order to evaluate the effectiveness of a gastric implant in an animal model of dietary obesity, silicone implants (2.5 ml) were inserted into the stomachs of male rats maintained on a chow or "cafeteria" diet. At the time of implantation, the cafeteria fed rats weighed 14% more than chow fed controls. Overweight cafeteria fed animals lost weight in response to the gastric implant, whereas control chow fed animals did not. Both implant groups had significant increases in stomach weights in contrast to sham implant groups, but the increase was much less in the cafeteria diet group. The fasting plasma levels of the gastrointestinal hormones, gastrin and pancreatic polypeptide, and oxytocin (a marker of vagal afferent function) were measured by radioimmunoassay. Cafeteria fed sham or implanted animals had significantly higher fasting levels of plasma oxytocin and gastrin, and significantly lower plasma levels of pancreatic polypeptide than the chow fed groups. These studies demonstrate that the gastric implant has more effect on weight in overweight animals on a palatable mixed diet, perhaps related to both mechanical and neural factors.     

Stereology of PCB 128-induced ultrastructural alterations in the rat liver

Hepatocyte cytoplasmic alterations were stereologically determined in male and female Sprague-Dawley rats fed PCB congener 128 (2,2',3,3',4,4'-hexachlorobiphenyl) in concentrations of 0.05, 0.5, 5, 50 ppm, or corn oil in diets daily for 13 weeks. A significant increase (p < 0.05) in the volume-fraction of smooth endoplasmic reticulum (SER) was measured in the female rats fed a diet containing 5 or 50 ppm of the congener and a significant increase was revealed in the male rats at doses of 0.5 and 50 ppm. Because drug metabolizing enzymes are bound to the SER, proliferated profiles may imply heightened enzyme activity necessary to metabolize the PCB. An elevation in volume-fraction of rough endoplasmic reticulum (RER) was measured in the hepatocytes of the male rats fed 5 ppm of the congener and none of the concentrations significantly enhanced the level of RER profiles in the females. The volume-fraction values of mitochondria, peroxisomes or lipid droplets of the hepatocytes in either the males or the females were not significantly different, as were the baseline volume-fraction of parameters studied between the male and the female rats. We determined for PCB 128, when administered in a diet to Sprague-Dawley rats, the no observable adverse effect level (NOAEL) is < 0.5 ppm.     

Zinc toxicity in the fowl: ultrastructural pathology and relationship to selenium, lead and copper

Some dietary, enzymic and morphological relationships of selenium, lead and copper to the toxicity of zinc in adult female fowls have been investigated. The anorexia, pancreatic and gizzard lesions which resulted from incorporating 20,000 and 25,000 mg zinc as zinc oxide per kg diet were not prevented by concurrent daily injections of 0.3 mg selenium or the addition of 500 and 2500 mg lead per kg diet. Anorexia and gizzard lesions were also produced by feeding copper sulphate at levels of 2000 and 4000 mg per kg of diet but the pancreas was unaffected. This suggests that zinc may act directly on the pancreas rather than by interfering with the protective function of the selenium. Glutathione peroxidase activity significantly decreased in the blood when zinc-containing diets were fed and selenium injection prevented this. Activity in the liver was also reduced but in the pancreas it was increased by both zinc and zinc plus selenium. Electron microscopy showed that there was an infiltration of heterophils in the gizzard of birds given excess zinc but otherwise there was little qualitative difference in surface cell ultrastructure from the degenerative processes of the normal desquamatory sequence. Pancreatic exocrine cells had reduced numbers of zymogen bodies, distended rough endoplasmic reticulum, many cytoplasmic small, electron-dense bodies and large autophagic vacuoles, sometimes leading to cell death. The acinar lumina were dilated and there was periacinar fibrosis. The significance of these lesions as an indication of zinc-induced interference with pancreatic protein synthesis and membrane integrity is discussed.     

Dietary fat content affects energy intake and weight gain independent of diet caloric density in rats

Recent considerations of high-fat diet hyperphagia have focused on fat's relatively high energy density as the critical variable which promotes overeating. However, a high-fat (HF) diet has been shown to enhance intake and weight gain relative to a high-carbohydrate (HC) diet when both energy density and palatability are equated [Am. J. Physiol. 269 (1995) R30]. The present studies investigated the generality of this finding across manipulations of diet caloric density, diet physical form, and chow availability. Separate groups of male rats were fed HF or HC at either 2.3 or 1.15 kcal/ml for 16 days; HF feeding enhanced weight gain relative to HC across both levels of energy density. HF hyperphagia also occurred when diets were presented in semisolid (gelled) form, and when chow was available in addition to liquid diet. These findings are consistent with previous observations that an HF diet can enhance daily kilocalorie intake and weight gain at least partly via a mechanism that is unrelated to caloric density.     

Consumption of a high-fat diet alters the homeostatic regulation of energy balance

Humans in many countries are currently experiencing what has been called an epidemic of obesity. That is, the average body weight (and amount of fat stored in the body) is increasing over years, carrying with it a multitude of associated medical, psychological, and economic problems. While there is no shortage of possible causes of this epidemic, increased availability and consumption of high-fat (HF), calorically dense and generally quite palatable food is often touted as a likely culprit. In order to better assess the impact of consuming a diet with those qualities, we have developed a well-controlled animal model in which the effects of chronic consumption of a high-fat diet can be dissociated from those of becoming obese per se. Long-Evans rats are fed one of two semipurified pelleted diets, a HF diet that contains 20% fat by weight and a low-fat (LF) diet that contains 4% fat by weight. Pair-fed animals consume the HF diet but are limited to the daily caloric intake of LF rats. Another group receives pelleted chow. Relative to animals consuming diets low in fat, HF animals weigh more, have more carcass fat, are hyperinsulinemic and hyperleptinemic, and are insulin resistant. HF-fed animals, independent of whether they become obese or not, also have central insulin and MTII insensitivity. Finally, HF rats have a down-regulated hypothalamic apo A-IV system that could contribute to their hyperphagia.     

Altered functional characteristics of rat macrophages during nephrosis. Synergistic effects of hypercholesterolemia.

The effects of alimentary hypercholesterolemia and nephrotic hyperlipidemia, alone and in combination, on rat peritoneal macrophage phagocytosis, basal eicosanoid production, and glomerular macrophage number during peak PA nephrosis were evaluated in rats fed four different diets: 1) normal/standard chow; 2) PA/standard chow; 3) normal/cholesterol-supplemented diet; and 4) PA/cholesterol-supplemented diet. Both PA/standard chow and normal/cholesterol-supplemented rodent groups manifested significantly greater peritoneal macrophage phagocytosis and glomerular macrophage number when compared with normal/standard chow animals. However, the combination of the nephrotic state with superimposed alimentary hypercholesterolemia (PA/cholesterol-supplemented group) produced the greatest rise in these parameters, a rise that was significantly greater than was produced in the three other groups. Regarding basal eicosanoid production by macrophages, there was a numerical trend toward increased production of thromboxane B2 in the PA/standard chow animals and normal/cholesterol-supplemented rats when compared with normal/standard chow. Again, the combination of nephrosis and alimentary hypercholesterolemia in the PA/cholesterol-supplemented group was associated with a significantly greater amount of thromboxane B2 generated when compared with the other three groups. Regarding PGE2 production, there were no significant differences among the groups, despite marked differences in fasting serum lipid levels. This data suggest that there is a synergistic effect between alimentary hypercholesterolemia and the secondary hyperlipidemia of nephrosis in producing these macrophage functional alterations. Because fasting triglyceride values between the two nephrotic groups were indifferent, one can further speculate that it is the elevation of the serum cholesterol value that predominantly evokes these changes in macrophage function.     

Inhibitors of sterol synthesis. Morphological studies in rats after dietary administration of 5 alpha-cholest-8(14)-en-3 beta-ol-15-one, a potent hypocholesterolemic compound

The morphological effects of short-term (9 days) dietary administration (0.1% in a laboratory chow diet) of 5 alpha-cholest-8(14)-en-3 beta-ol-15-one, a novel regulator of cholesterol metabolism with significant hypocholesterolemic activity, has been studied in young male rats. Control animals included rats fed the basal diet ad libitum and a series of rats pair-fed to the individual experimental animals. At the time of necropsy, the morphological changes in rats which have been observed in rats following treatment with other absorbable hypolipidemic agents (myeloid bodies with triparanol, increased peroxisomes with clofibrate, and proliferation of smooth endoplasmic reticulum with compactin and mevinolin) were not apparent on ultrastructural examination of livers of rats treated with the 15-ketosterol. Two changes were observed in the rats fed the 15-ketosterol: a decrease in adipose tissue and enlargement of the small intestine. Diminished fat was also noted in the pair-fed controls and was presumably due to decreased food consumption. The intestines of rats fed the 15-ketosterol were morphometrically most enlarged in the jejunal region. Morphologically, this increase was distinguished by increased depth of crypts of Lieberkuhn and pseudostratification of epithelium at the base of the villi. These changes were qualitatively and quantitatively similar to the adaptive changes reported in the rat after resection of small bowel or following intestinal bypass (segment of bowel remaining in continuity). The morphological changes induced in the rat by administration of the 15-ketosterol were not observed in 4 baboons which received the compound orally at doses of 50, 75, or 100 mg per kilogram of body weight for up to 3 months.     

Epithelial markers for paraffin-embedded human tissues

Summary To assess the effect of ethanol on the liver of the offspring of alcohol-fed rats, the hepatocytes of newborn rats whose mothers were fed: a) a liquid diet containing alcohol, b) the same diet isocalorically balanced, or c) a chow diet, were analyzed using both quantitative and qualitative electron microscopy as well as cytophotometric and biochemical methods.Hepatocytes of chow-fed and pair-fed controls showed differences in the amounts of glycogen and lipids as well as in several stereologically measured variables including mitochondria, Golgi apparatus and smooth endoplasmic reticulum. These differences are probably due to the composition of the diet.Rats prenatally exposed to alcohol showed increases in the hepatocyte and mitochondria volumes and in the number of peroxisomes Moreover, the Golgi apparatus of these cells appeared disorganized and composed exclusively of small size vesicles, suggesting an impairment of their function.     

Lack of diet-induced thermogenesis following lesions of paraventricular nucleus in rats

The effects of electrolytic lesions in the hypothalamus paraventricular nucleus were studied in adult male and female Sprague-Dawley rats, fed different diets, consisting of either palatable human food plus chow (cafeteria diet) or chow alone. The results showed that both cafeteria diet and lesions induced an increase in energy intake and weight gain in rats of both sexes. Oxygen consumption rate and colonic temperature were significantly decreased by lesions, while cafeteria diet increased the same parameters only in intact animals. The lesion decreased weight, protein and DNA, and temperature of brown adipose tissue, while cafeteria diet increased the values considered in brown adipose tissue of sham-injured rats, but not in lesioned animals. The response to norepinephrine administration was significantly greater in intact rats and those fed cafeteria diet. The results suggest that the larger body weight gain observed in lesioned rats, particularly evident in rats fed cafeteria diet, is partly due to the disappearance of diet-induced thermogenesis that depends on the reduced mass and functional activity of brown adipose tissue.     

Preference for high carbohydrate over various high fat diets by diabetic rats

Streptozotocin-diabetic male rats were hyperphagic relative to nondiabetic controls when offered only high carbohydrate (CHO) laboratory chow. Diabetics and controls ate about the same amount of high fat diets made from 67% w/w chow and 33% either coconut oil (saturated) or safflower oil (unsaturated). However, when offered a simultaneous choice of high fat diets and chow, nondiabetics and low dose (35 mg/kg) streptozotocin-diabetics showed a preference for the high fat diet: in contrast the high dose (65 mg/kg) streptozotocin diabetics developed a preference for chow. When pairs of isocaloric synthetic diets were offered, diabetics again preferred low fat/high CHO to high fat/low CHO diets, but the actual intake of fat was not constant across different diet pairs. Nondiabetics also selected away from the high fat diets in these synthetic diet pairs, even when saccharin was added to the high fat diet in an attempt to equate its sweetness with that of the paired low fat-high CHO diet. Plasma ketone levels of diabetics during obligatory high fat diet consumption were negatively correlated with their subsequent preference for the fat diet over simultaneously-offered chow. These data show that strong dietary preferences do not develop for fat in diabetics and suggest that high fat diets do not have net beneficial postingestional effects in these rats.     

The effect of consumption of the pyrrolizidine alkaloid-containing plant Senecio jacobaea on iron and copper metabolism in the rat

The effect of dietary tansy ragwort (Senecio jacobaea), a pyrrolizidine alkaloid (PA)-containing plant, on mineral metabolism in rats was studied. In experiment 1, rats were fed a dietary level of 5% tansy ragwort. At intervals of 1, 2, 4, 6 and 8 weeks animals were killed and tissue mineral levels determined. As compared to comparable controls, rats fed tansy ragwort showed by 6 weeks elevated liver and spleen copper and iron levels. Experiment 2 was a 3 X 4 factorial experiment with added dietary copper levels of 0, 50 and 250 ppm, and tansy ragwort levels of 0, 1, 2.5 and 5%. Liver copper levels increased markedly with increasing levels of tansy ragwort; at 0, 50 and 250 ppm added copper, liver copper levels were 4, 18 and 21 times greater in rats fed 5% tansy ragwort as compared to those with no tansy ragwort. Increases in liver iron and spleen copper were noted with consumption of tansy ragwort. Higher liver copper levels were observed when a casein-based diet rather than a soybean meal diet was used, suggesting an effect of phytate in soybean meal in reducing copper absorption. In the last experiment, 59Fe was administered to rats fed diets with or without tansy ragwort. After 5 weeks on tansy ragwort, rats showed very low levels of 59Fe in erythrocytes, tibia and liver, and elevated levels in spleen and kidney, suggesting either an impairment of hematopoesis or accelerated erythrocyte destruction as a result of PA consumption. These results indicate that PA's cause increased liver copper content, and disturbances in iron metabolism.     

Differential effects of chow and purified diet on the consumption of sucrose solution and lard and the development of obesity

Obesity has been associated with increased consumption of sweetened beverages and a high-fat diet. We determined whether the composition of the dry pellet offered with liquid sucrose (LS) and lard influenced the development of obesity. We hypothesized that animals offered LS or LS and lard (choice), in addition to chow or purified low fat diet pellet (LFD; 10% fat), would gain more body fat than controls. We compared the effects of LFD vs. chow on voluntary consumption of LS and lard, serum triglyceride (TG), glucose, and body fat over 21 days. Male Sprague Dawley rats (n=10/group) were offered chow, chow+LS, chow choice, LFD, LFD+LS, LFD choice or solid high-sucrose diet (70% sucrose). Energy intakes of rats fed chow, LFD, and high-sucrose diets were similar. Energy intake was increased by 16% in chow+LS, 15% in LFD+LS, 11% in LFD choice, and 23% in chow choice rats. Chow choice rats consumed 142% more lard than LFD choice rats. Fasting glucose increased in all choice rats compared with the chow and high-sucrose diet rats. Fasting TG increased in LFD choice rats and were ~75% higher than those of chow, LFD, or high-sucrose rats. Chow choice had higher carcass fat than chow, chow+LS, and LFD groups however LFD choice was not different from their controls. Another experiment confirmed rats consumed 158% more lard when given chow choice compared to LFD choice. The diet offered to rats with free access to LS and lard influenced the development of obesity, sucrose and lard selection, and TG.     

Diets rich in saturated fat and fructose induce anxiety and depression‐like behaviours in the rat: is there a role for lipid peroxidation?

Epidemiological studies reveal associations between obesity/metabolic syndrome and mood disorders. We assessed behavioural changes in rats fed diets enriched in fat and fructose in different proportions and correlated the observed alterations with biochemical changes induced by the diets. Three groups of rats were used as follows: control (C) animals fed regular rat chow, rats fed high‐fat diet (HF) and rats fed high‐fat and high‐fructose diet (HFHF). HF and HFHF animals were also given a 10% fructose solution as drinking water. Behavioural and biochemical parameters were determined. Anxiety was measured by the open‐field and the social interaction test. Depression‐like behaviour was evaluated by the forced swimming test. The object recognition test was utilized to assess effects on memory. Diet‐exposed animals displayed signs of anxiety in the open‐field (HF rats had reduced central time; HFHF rats had reduced number of central entries) and in the social interaction test (decreased time of interaction in HF group). In the forced swimming test, the immobility time was prolonged in the HFHF group. While different measures of anxiety scores correlated with visceral adiposity and dyslipidemia, results from both social interaction and forced swimming tests were significantly associated with lipid peroxidation, which in turn also correlated with the metabolic parameters. The experimental diets did not affect the object recognition memory. Both experimental diets induced metabolic derangements in rats and provoked similar anxiety‐ and depression‐like behaviours. Lipid peroxidation seems to play a role in translating diet‐induced metabolic alterations into behavioural disorders.     

Correlation of parameters of cadmium exposure with onset of cadmium-induced nephropathy in rats

Rats were injected daily, five days/week, with 0.6 mg Cd/kg as CdCl2 for eight weeks. Groups of rats were sacrificed weekly. Urine, plasma and tissue cadmium levels, and morphology of renal cortex were studied. No abnormal effects were found until the fifth or sixth week when cadmium in kidney reached about 100 micrograms/g tissue. At this time, renal tubular lining cells showed an increase in lysosomes, microbodies and smooth endoplasmic reticulum and a low molecular weight cadmium-binding species was detectable in plasma. These changes were followed by the onset of glycosuria and proteinuria, accompanied by abnormal mitochondrial morphology. This progressed to cellular swelling and finally necrosis at the seventh and eighth weeks when cadmium concentration of the kidney reached about 200 micrograms/g of tissue. It is concluded that there are two phases in the development of cadmium induced nephropathy. Phase I is an adaptive phase characterized by some increase in smooth endoplasmic reticulum, microbodies and secondary lysosomes and the presence of metallothionein intracellularly in liver and kidney, but no detectable metallothionein in plasma and no increase in urinary cadmium. Phase II is a toxic phase characterized by detectable low molecular weight cadmium-binding species in plasma and evidence of renal tubular dysfunction followed by lethal injury to renal tubular lining cells.