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 effect of dietary protein restriction on high dose gentamicin nephrotoxicity in rats

Gentamicin (120 mg/kg/day) was administered for 10 days to Sprague-Dawley rats given either a low (5% w/w) or normal (18% w/w) protein diet. Serum protein concentrations remained normal in all rats during the study. Nephrotoxicity was slightly less severe in rats fed a low protein diet as shown by: (i) a mean creatinine clearance rate (14 +/- 4 ml/min) which was significantly greater than that (8 +/- 3 ml/min) recorded from the rats maintained on the normal diet (P less than 0.05); (ii) lower activities of urinary N-acetyl-beta-D glucosaminidase (NAG); and (iii) less marked histological changes. Mean tissue concentrations of gentamicin were considerably lower in both renal cortex and medulla from rats maintained on the low protein diet than from those animals on the normal diet (P less than 0.01 and P less than 0.05, respectively). These differences were, however, not reflected in the mean trough serum gentamicin concentrations which were not significantly different between the two groups. These results are discussed in relation to the proposed mechanisms involved in gentamicin-induced nephrotoxicity.     

The effect of dietary protein restriction on high dose gentamicin nephrotoxicity in rats.

Gentamicin (120 mg/kg/day) was administered for 10 days to Sprague-Dawley rats given either a low (5% w/w) or normal (18% w/w) protein diet. Serum protein concentrations remained normal in all rats during the study. Nephrotoxicity was slightly less severe in rats fed a low protein diet as shown by: (i) a mean creatinine clearance rate (14 +/- 4 ml/min) which was significantly greater than that (8 +/- 3 ml/min) recorded from the rats maintained on the normal diet (P less than 0.05); (ii) lower activities of urinary N-acetyl-beta-D glucosaminidase (NAG); and (iii) less marked histological changes. Mean tissue concentrations of gentamicin were considerably lower in both renal cortex and medulla from rats maintained on the low protein diet than from those animals on the normal diet (P less than 0.01 and P less than 0.05, respectively). These differences were, however, not reflected in the mean trough serum gentamicin concentrations which were not significantly different between the two groups. These results are discussed in relation to the proposed mechanisms involved in gentamicin-induced nephrotoxicity.     

Protective effect of trans-resveratrol on gentamicin-induced nephrotoxicity

Reactive oxygen species (ROS) have been involved in glomerular filtration rate (GFR) reduction observed after gentamicin treatment. trans-Resveratrol (TR), a natural hydroxystilbene, has been identified to be a potent inhibitor of ROS production. The aim of this work has been to study whether TR has a protective effect on gentamicin-induced nephrotoxicity in vivo and the effect of TR on lipid peroxidation and the oxidative stress induced by gentamicin. Animals that received a daily intraperitoneal injection of gentamicin (100 mg/kg body weight) showed lower GFR and renal blood flow (RBF) and higher urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) than control rats. Rats receiving TR together with gentamicin showed higher GFR and RBF and lower NAG urinary excretion than rats receiving gentamicin alone. Moreover, renal lipid peroxidation increased in rats receiving gentamicin alone, and this increase was prevented by the administration of TR. The concentration in plasma of antioxidants was higher in the group that received TR with gentamicin than in the gentamicin and control groups. The activities of lactate dehydrogenase and alkaline phosphatase were higher in rats treated with gentamicin than in control rats and were reduced by the treatment with TR. This study demonstrates an improvement in renal function in response to the administration of TR in gentamicin-induced nephrotoxicity. At least a part of this effect of TR could be based on its antioxidant activity.     

Meal composition influences subsequent food selection in the young rat

Food selection one-half hour after the ingestion (2 g) of either a protein containing or a protein-free (carbohydrate) diet was studied in young rats. Following a 12 hr fast the rats were allowed 15 minutes to consume the meal (premeal). Thirty minutes later, they had access to two isocaloric diets that differed only in protein and carbohydrate content. During the first hour of ad lib feeding, protein intake and protein concentration selected were lower in the 45% casein prefed group compared to the carbohydrate group. A further reduction in protein intake and protein concentration occurred when the protein content of the premeal was increased to 70% from 45% casein. Rats prefed with the 70% casein diet significantly reduced their daily total food intake (12 hr) compared to either the 45% casein or carbohydrate prefed group. It is concluded that both quantity and composition of food selected is influenced by the composition of the preceding meal.     

Effects of hippocampal lesions on adaptive intake of diets with disproportionate amounts of amino acids

Bilateral double electrolytic overlapping lesions were placed in dorsal-lateral hippocampus of male 230 g rats, and their food intake responses to the ingestion of diets containing disproportionate amounts of amino acids were examined. Rats with such lesions and intact control rats maintained their normal intakes of the 6% casein basal diet or a threonine basal amino acid diet postoperatively. However, they exhibited marked initial food intake depression, similar to that of intact rats, when fed the threonine imbalanced amino acid diet. Also, animals with lesions in certain areas of the dorsal-lateral hippocampus showed facilitated adaptation to the amino acid imbalanced diet. Similar severe reduction in food intake with relative lack of adaptation were observed in both the intact controls and rats with hippocampal lesions when fed amino acid diets completely devoid of threonine. Initial food intake of rats with hippocampal lesions was inhibited drastically as was the case with the intact controls when fed a 75% casein high protein diet. All rats, either intact or lesioned, showed similar slow adaptation patterns with the prolonged ingestion of the high protein diet. The initial food intake responses and facilitated adaptation of the animals bearing lesions in certain areas of the hippocampus suggest that such areas are not crucially involved in the inhibition of food intake of rats fed disproportionate amounts of dietary amino acids. Rather, such areas of lesions in the hippocampus may play a role in a system governing the behavioral adaptation of the intake of amino acid imbalanced diets but not of diets containing amino acids in general excess. This would also indicate that different mechanisms control the intake of amino acid imbalanced diets and diets containing amino acids in excess.     

Effects of dietary sugar and of dietary fat on food intake and body fat content in rats

The long term ingestion of a sugar-rich diet (low fat) caused severe obesity in adult rats. In a separate experiment, the habitual consumption of a fat-rich diet (40% kcal from fat) also caused severe obesity. Severe obesity developed in both groups of animals even though they did not overeat. Voluntary food intake for the sugar-fed rats averaged 28,314 +/- 756 calories/rat per 55 wks which was similar to the value of 28,884 +/- 953 calories/rat per 55 wks for the fat-fed rats. However, both values were lower than that of 32,869 +/- 588 for the control rats eating Purina chow. Despite a lower caloric intake, carcass fat averaged 45 +/- 1% for rats eating the sugar-rich diet and 46 +/- 2% for rats eating the fat-rich diet, but only 33 +/- 2% for rats eating a diet of Purina chow. These results provide evidence that severe obesity can develop in the absence of hyperphagia in animals eating a sugar-rich or fat-rich diet. Finally, a rat model for severe obesity is presented in which carcass fat ranged from 18% (lean) to 61% (severe obesity) using dietary intervention alone at critical stages of the animal's life.     

Maternal malnutrition in the rat: Effects on food intake and body weight

The effects of dietary protein level on food intake and body weight were examined in adult female rats during a 35-day pre-mating period and during gestation and lactation. During the pre-mating period, no differences in daily food intake were observed among rats fed a 6% casein, 8% casein or 25% casein diet. However, during this period, rats fed the 6% casein diet gained significantly less weight than those with ad lib access to the 8% or 25% casein diets or than rats pair-fed the 25% casein diet in amounts equivalent to that consumed by rats in the 6% or 8% casein groups. Additionally, rats fed the 6% casein diet displayed decreased efficiency of energy utilization, calculated as weight gain per 100 kilocalories consumed, relative to rats fed the 8% or 25% casein diets. No differences in food intake were observed among the groups during gestation. However, rats fed the 6% casein diet gained less weight than rats fed the 8% or 25% casein diets. During lactation rats fed either the 6% or 8% casein diet consumed significantly less food than animals given the 25% casein diet ad lib. During the second week of lactation, rats receiving ad lib access to the 25% casein diet gained weight while those receiving the 6% or 8% casein diets continued to lose weight. At parturition, body weights of pups did not differ as a function of dietary condition. However, by day 12 of life, pups whose dams had ad lib access to the 25% casein diet weighed significantly more than pups whose dams consumed the 6% or 8% casein diet or whose dams were pair-fed the 25% casein diet in amounts equivalent to those consumed by rats fed the 6% or 8% casein diet.     

Effects of dietary protein on food and water intake in spontaneously hypertensive rats

We have been studying the development of hypertension in spontaneously hypertensive rats (SHR) fed a low protein diet. The effects of a low protein diet upon food and water intake were examined. Body weight gain, food and water intake were measured in three to twenty-three week-old SHR and Wistar Kyoto rats (WKY) fed diets containing 8%, 15% or 25% casein. Body weights of SHR and WKY fed an 8% casein diet were significantly lower at 23 weeks than rats on the higher protein diets, although both groups on the 8% diet consumed more food and water per g of body weight. In addition, SHR fed an 8% casein diet drank less water per gram of food than WKY or SHR fed 15% and 25% casein diets. These results indicate that changes in food and water intake, as a consequence of low protein diets, should be an additional consideration when examining the effects of dietary protein on the development of hypertension.     

Influence of dietary protein level on protein self-selection and plasma and brain amino acid concentrations

Control of protein intake was studied in young rats that were allowed to choose between either protein-free and 55% casein diets or 15% and 55% casein diets. Animals on the protein-free vs. 55% casein regimen exhibited a lower weight gain, a lower cumulative energy intake and a greater cumulative total protein intake during the 13-day study compared to rats selecting between 15% and 55% casein. The daily average proportion of total food selected as casein by animals choosing between protein-free and 55% casein diets increased from 15% to 38% during the course of the study. In contrast, rats choosing between 15% and 55% casein chose 18-22% of total food as protein throughout the entire study. Long-term protein intake or protein selection did not correlate significantly with whole-brain contents of 5-HT or 5-HIAA. Our results suggest that protein intake is not regulated at a constant proportion of total calories, but is controlled between a minimum level that will support rapid growth and a maximum that, if exceeded, would require the animal to undergo substantial metabolic adaptation. The mechanism controlling protein selection may involve diet-induced changes in the brain content of total free indispensable amino acids.     

Protein selection by rats adapted to high or moderately low levels of dietary protein.

After preliminary studies on flavor acceptability, patterns and indices of subsequent feeding behavior were monitored by computer in young rats which were adapted to 15% or 70% casein diets before being offered, sequentially, choices between flavored diet pairs in which the proportions of percentage casein were 5/65, 5/55, 5/45, 5/35 and 5/25. Similarly adapted rats received these choices in the reverse sequence. Rats adapted to 15% casein usually ate randomly from the diet pairs and selected approximately 15-30% casein; individual behaviors were prominent. The 70% casein groups avoided the higher casein diet, often within minutes (except for the first-offered 5/25 choice), and seldom selected more than 10% casein; individual differences were infrequent. Such rats also distinguished between flavored 70% and 65% casein diets. Sizes and numbers of meals and rates of eating differed for the paired diets, especially for rats adapted to 70% casein. A flavor added to the 70% casein adaptation diet was not avoided when present only in the 5% casein diet of a 5/65 choice. Rats adapted to 70% soy protein before receiving flavored 5/65 to 5/25 choices selected 20-28% soy protein, a level far above those of casein selections by rats adapted to 70% casein. Dietary adaptation and type of protein thus affect subsequent diet selection and feeding patterns and indices.     

Dietary sardine protein lowers insulin resistance, leptin and TNF-α and beneficially affects adipose tissue oxidative stress in rats with fructose-induced metabolic syndrome

The present study aims at exploring the effects of sardine protein on insulin resistance, plasma lipid profile, as well as oxidative and inflammatory status in rats with fructose-induced metabolic syndrome. Rats were fed sardine protein (S) or casein (C) diets supplemented or not with high-fructose (HF) for 2 months. Rats fed the HF diets had greater body weight and adiposity and lower food intake as compared to control rats. Increased plasma glucose, insulin, HbA1C, triacylglycerols, free fatty acids and impaired glucose tolerance and insulin resistance was observed in HF-fed rats. Moreover, a decline in adipose tissues antioxidant status and a rise in lipid peroxidation and plasma TNF-α and fibrinogen were noted. Rats fed sardine protein diets exhibited lower food intake and fat mass than those fed casein diets. Sardine protein diets diminished plasma insulin and insulin resistance. Plasma triacylglycerol and free fatty acids were also lower, while those of α-tocopherol, taurine and calcium were enhanced as compared to casein diets. Moreover, S-HF diet significantly decreased plasma glucose and HbA1C. Sardine protein consumption lowered hydroperoxide levels in perirenal and brown adipose tissues. The S-HF diet, as compared to C-HF diet decreased epididymal hydroperoxides. Feeding sardine protein diets decreased brown adipose tissue carbonyls and increased glutathione peroxidase activity. Perirenal and epididymal superoxide dismutase and catalase activities and brown catalase activity were significantly greater in S-HF group than in C-HF group. Sardine protein diets also prevented hyperleptinemia and reduced inflammatory status in comparison with rats fed casein diets. Taken together, these results support the beneficial effect of sardine protein in fructose-induced metabolic syndrome on such variables as hyperglycemia, insulin resistance, hyperlipidemia and oxidative and inflammatory status, suggesting the possible use of sardine protein as a protective strategy against insulin resistance and related situations.     

Role of inhibitor of apoptosis protein in gentamicin-induced cochlear hair cell damage

Apoptotic cell death is considered to play a key role in gentamicin-induced cochlear hair cell loss. Inhibitor of apoptosis proteins (IAPs) are important regulators of apoptosis that can prevent activation of effector caspases. This study was designed to investigate the possible involvement of X-linked inhibitor of apoptosis protein (XIAP) in hair cell death due to gentamicin. Basal turn organ of Corti explants from postnatal day (p) p3 or p4 rats were maintained in tissue culture and were exposed to 35 muM gentamicin for up to 48 h. Effects of specific XIAP inhibitors on gentamicin-induced hair cell loss and caspase-3 activation were examined. XIAP inhibitors increased gentamicin-induced hair cell loss but an inactive analog had no effect. Caspase-3 activation was primarily observed at 36 or 48 h in gentamicin-treated hair cells, whereas caspase-3 activation peaked at 24-36 h when explants were treated with gentamicin and an XIAP inhibitor. The inhibitors alone had no effect on hair cells. Finally, a caspase-3 inhibitor decreased caspase-3 activation and hair cell loss induced by gentamicin and an XIAP inhibitor, but caspase-8 and -9 inhibitors did not. The results indicate that XIAP normally acts to decrease caspase-3 activation and hair cell loss during gentamicin ototoxicity, as part of a protective response to potentially damaging stimuli.     

Exaggerated response to gentamicin-induced nephrotoxicity in Sprague-Dawley rats: identification of a highly sensitive outlier population

A number of factors have been shown to predispose patients treated with aminoglycosides to nephrotoxicity. In a previous study in our laboratory investigating the interaction of prior renal dysfunction with gentamicin toxicokinetics, 9.4% of rats in all treatment groups were relatively more sensitive to gentamicin-induced nephrotoxicity. To determine if these outliers had an underlying disease or physiological abnormality, serum was collected from 99 Sprague-Dawley rats prior to daily treatment with 75 mg/kg gentamicin for seven days. Urea nitrogen, creatinine, Na, K, Ca, Mg, P, total protein, albumin, aspartate transaminase, serum osmolality, total white and red blood cell count, hematocrit, hemoglobin, blood gases, and thyroxine were measured. Blood was collected one and four hours after the first dose of gentamicin for pharmacokinetic analysis. Elevations in post-treatment creatinine and nitrogen were significantly greater in the outliers (4.10 +/- 0.24 mg/dl (n = 12) vs 1.92 +/- 0.06 mg/dl (n = 87) and 146.4 +/- 7.2 mg/dl (n = 12) vs 71.5 +/- 2.0 mg/dl (n = 87); both p = 0.0001) and served as criteria for identifying this subgroup. Post-treatment creatinine and urea nitrogen were not normally distributed in the entire study population. However, when the population was divided into normal and sensitive subgroups, both subgroup values were normally distributed. The gentamicin pharmacokinetic profiles were similar in both groups. Postmortem histopathology showed significant increases in tubular casts and tubular necrosis (p = 0.01) in the sensitive rats, compared to the normally responding subgroup.(ABSTRACT TRUNCATED AT 250 WORDS)     

Calcium supplementation and thyroid hormone protect against gentamicin-induced inhibition of proximal tubular Na+,K(+)-ATPase activity and other renal functional changes.

Gentamicin can cause proximal tubule necrosis. We have shown that inhibition of PT Na+,K(+)-ATPase activity is rapidly induced by gentamicin. We have now investigated whether manipulations known to attenuate the negative effects of gentamicin on renal excretory capacity, i.e. high calcium intake and L-thyroxine treatment, will also attenuate gentamicin-induced inhibition of Na+,K(+)-ATPase activity and ameliorated signs of proximal tubule damage. Rats were gentamicin- or vehicle-treated for 7 days. Sub-groups were given 4% calcium (Ca) supplements or L-thyroxine 20 micrograms 100 g-1 body weight daily. Gentamicin significantly reduced the glomerular filtration rate and increased the urinary excretion of the proximal tubule lysosomal enzyme, N-acetyl-beta-D-glucosaminidase. Gentamicin significantly reduced proximal tubule Na+,K(+)-ATPase activity, measured in single permeabilized proximal tubule segments. Sodium excretion was inversely correlated to proximal tubule Na+,K(+)-ATPase activity. Both calcium and L-thyroxine alleviated all gentamicin-induced side-effects on renal function as well as on proximal tubule Na+,K(+)-ATPase activity. Calcium and L-thyroxine had no significant effect on renal function. L-thyroxine, but not calcium, increased proximal tubule Na+,K(+)-ATPase activity in control rats. Renal cortical tissue gentamicin concentration was not influenced by calcium but was significantly lowered by L-thyroxine. Two procedures which, via different mechanisms, afford protection from gentamicin-induced changes in renal function also give protection from gentamicin-induced inhibition of Na+,K(+)-ATPase activity. This suggests that loss of integrity of the Na+,K(+)-ATPase enzyme contributes to gentamicin-induced nephrotoxicity.     

The effects of early dietary experience on subsequent protein selection in the rat

Two series of experiments were designed to investigate the effects of protein composition of the first solid food consumed by young rat pups on their subsequent protein intake after weaning. In the first series of experiments, pups were allowed access to the maternal diet between 17 and 21 days of age, then weaned to a choice of 10% and 60% casein diets at 21 days. Pups with access to a maternal diet containing 39% casein selected high levels of protein (calculated as % of total calories selected as protein: 50 +/- 1% (access) vs. 29 +/- 3.5% (no access), p less than 0.05), whereas lower levels of protein were selected following access to a maternal diet containing 26% casein (16 +/- 1.1% (access) vs. 23 +/- 1% (no access), p less than 0.05) or 10% casein (27 +/- 3.9% (access) vs. 39 +/- 3.7% (no access), p less than 0.05). In a second series of experiments, the influence of early diet composition on subsequent protein selection was confirmed by prematurely weaning rats at 17 days of age to either 39% or a 10% casein diet. When given a choice of 10% and 60% casein diets at 21 days, pups selected higher levels of protein if weaned to a 39% casein diet as compared to a 10% casein diet (37 +/- 5.0% vs. 19 +/- 3.5% (p less than 0.05) for the first experiment and 43 +/- 3.0% vs. 26 +/- 4.0% (p less than 0.05) in a second experiment). It was concluded that the level of protein selected by young rats is positively correlated with the protein concentration of their first solid food.     

Effect of pre-feeding ammonium acetate on food intake of rats fed high protein diets

The effect on intake of a 75% casein diet after prefeeding for one week a 6% casein basal diet with additional 0%, 2%, 5%, 8% or 15% ammonium acetate was examined in rats trained to eat in three hours per day. Food intake was measured from 0-15, 15-30, 30-90, and 90-180 minutes for the first two days that the ammonium acetate diets were presented. Rats eating 5% and 8% or 15% ammonium acetate diet depressed their intake significantly for one day and for four days respectively. Rats eating 2%, 5%, 8%, or 15% ammonium acetate diets depressed their intake significantly from 0-30 minutes. When presented with the 75% casein diet, rats prefed 0% to 5% and 8% and 15% ammonium acetate diets ate 55% to 58% and 72% and 94% of their respective baseline intakes. It is suggested that prefeeding 15% ammonium acetate apparently induces sufficient metabolic adaptation to ammonia intake so that the rat is able to offset the metabolic consequences of intake of the 75% casein diet, thus preventing the usual food intake depressing effect of the high protein diet.     

Protein selection, food intake, and body composition in response to the amount of dietary protein

Though not universally observed, moderately low-protein diets have been found to increase caloric intake and body fat. It appears that animals overeat in calories in order to obtain more dietary protein. For animals to control protein intake, they must be able to distinguish between two isocaloric diets containing different percentages of protein and make the appropriate dietary selection on the basis of their previous history of protein intake. Experiment 1 examined the 24-h diet selection (5 vs. 35% casein) of Sprague-Dawley rats that had been previously fed diets containing various percentages of dietary protein (5, 10, 20, 35, or 60% casein). Animals fed 5, 10, or 20% dietary protein showed a preference for the higher protein selection diet. In contrast, no significant diet preference was found in animals pre-fed the two higher levels of dietary protein (35 or 60% casein). In this study, daily food intake and body fat of rats fed the low-protein diets (5 and 10% casein) were similar to rats fed the 20% casein diet. Experiment 2 examined the effects of the level of methionine supplementation on rats fed 10% casein. In this study, food intake and body fat were increased by approximately 20% in rats fed 10% casein diets, regardless of the level of methionine supplementation (0.3 vs. 0.15%). Together, the results suggest that the presence of low-protein-induced hyperphagia helps maintain body protein levels in the face of moderately low dietary protein and promotes an increase in the amount of body fat and energy.     

Protective role of aminoguanidine on gentamicin-induced acute renal failure in rats

The toxicity of aminoglycosides including gentamicin (GEN), the most widely used drug in this category, is believed to be related to the generation of reactive oxygen species (ROS) in the kidney. Aminoguanidine (AG) is known as an effective antioxidant and its free radical scavenger effects may protect GEN-induced acute renal failure (ARF). Therefore, this study was focused on investigating the possible protective effect of AG against GEN-induced nephrotoxicity in an in vivo rat model. We investigated the effects of AG on GEN-induced changes in renal tissue malondialdehyde (MDA) levels; nitric oxide (NO) generation; glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) activities; glutathione (GSH) content; serum creatinine (Cr) and blood urea nitrogen (BUN) levels. Morphological changes in the kidney were also examined using light microscopy. GEN administration to control group rats increased renal MDA and NO levels but decreased GSH-Px, SOD, CAT activities and GSH content. AG administration with GEN injection resulted in significantly decreased MDA, NO generation and increased GSH-Px, SOD, CAT activities and GSH content when compared with GEN alone. Serum levels of Cr and BUN significantly increased as a result of nephrotoxicity. Also, AG significantly decreased Cr and BUN levels. Morphological changes in the kidney, including tubular necrosis, intracellular edema, glomerular and basement membrane alterations were evaluated qualitatively. Both biochemical findings and histopathological evidence showed that administration of AG reduced the GEN-induced kidney damage. We propose that AG acts in the kidney as a potent scavenger of free radicals to prevent the toxic effects of GEN both at the biochemical and histological level.     

Dietary self-selection vs. complete diet: body weight gain and meal pattern in rats.

Food intake and body weight gain of male adult Wistar rats were examined in two groups of animals. One group (n = 14) was allowed to select its diet from separate sources of protein (casein, 3.1 kcal/g), fat (lard and sunflower oil, 7.9 kcal/g) and carbohydrate (CHO, starch and sucrose, 3.3 kcal/g). Another group (n = 10) received a nutritionally complete diet (3.3 kcal/g). After 2 weeks of adaptation to the diets, body weights and meal patterns were recorded for at least 4 days. The total caloric intake was nearly identical for the two groups of rats. Rats given dietary choice gained less weight over 4 days than rats fed chow and showed reduced feed efficiency. During the 24-h period, self-selecting rats consumed 20.8% of calories as proteins, 21% as fats and 58.2% as CHO. Self-selecting rats ate significantly less calories during the day than did rats given chow. The chow diet consisting of 17.3% calories as protein, 7.6% as fat and 75.1% as CHO. When comparing the self-selecting group nutrient intakes to those of chow-fed group it was observed that 24-h protein calorie intakes were identical in both groups. Fat intake was significantly higher and CHO reduced as compared to chow-fed rats. During the day, CHO intake was higher in self-selecting rats, and fat intake was not significantly reduced. During the night, protein and fat intakes were significantly higher in self-selecting rats, while CHO intake was significantly decreased, particularly in the last periods of the night.(ABSTRACT TRUNCATED AT 250 WORDS)