Isocaloric Sucrose Research Articles

No effect of chronic ethanol administration on the activity of alcohol dehydrogenase and aldehyde dehydrogenases in the near-term pregnant guinea pig

The objective of this study was to determine the effect of chronic maternal administration of moderate-dose ethanol on alcohol dehydrogenase, low Km aldehyde dehydrogenase, and high Km aldehyde dehydrogenase activities in the guinea pig at near-term pregnancy. The activity of each enzyme in the maternal liver, fetal liver, and placenta of the guinea pig at 59 days of gestation (term, 66 days) was determined spectrophotometrically following chronic daily oral administration of two doses of 1 g ethanol/kg maternal body weight or isocaloric sucrose solution. There was no experimental evidence of ethanol-induced malnutrition in the mother or growth retardation in the fetus. There was a statistically significant increase (65%) in the microsomal cytochrome P-450 content of the maternal liver for the ethanol treatment compared with the sucrose treatment. The alcohol dehydrogenase, low Km aldehyde dehydrogenase, and high Km aldehyde dehydrogenase activities in the maternal liver, fetal liver, and placenta were not statistically different for the ethanol-treated compared with the sucrose-treated animals. This also was the case for the maternal blood and fetal blood ethanol and acetaldehyde concentrations, determined at 2h after maternal administration of 1 g ethanol/kg maternal body weight. These data demonstrate that the ethanol- and acetaldehyde-oxidizing enzyme activities in the maternal-placental-fetal unit of the guinea pig at near-term pregnancy were not changed by chronic administration of moderate-dose ethanol.

Effect of ethanol and vitamin B6 deficiency on pyridoxal 5-phosphate levels and fetal growth in rat.

The effects of chronic ethanol consumption and dietary vitamin B6 levels on tissue pyridoxal 5-phosphate (PLP) contents and rat fetal development were investigated. Pregnant Sprague-Dawley rats were given 35% ethanol-calorie liquid diet with either adequate B6 (1.7 mg/liter) or deficient B6 (0.17 mg/liter), ad libitum, from gestation days 7 to 21. Control groups (adequate control and deficient control) were pair-fed with isocaloric sucrose substituted for ethanol. Rats were killed on gestation day 21. Ethanol groups had smaller fetuses than control groups, regardless of their dietary B6 levels. However, in B6 deficiency, ethanol affected fetal weight more severely than in B6 adequate state. Tissue PLP levels were determined by radioenzymatic method. In B6 deficiency, ethanol feeding reduced maternal liver PLP by 22%. PLP in other tissues were not affected by ethanol. These results confirmed that chronic alcohol consumption affected fetal growth and also provided evidence that B6 deficiency exacerbated ethanol effect.

Alcohol effects on LH and FSH in ovariectomized female monkeys

The acute effects of alcohol (2.5, 3.0, 3.5 g/kg) and sucrose control solution on basal levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) were compared in recently and chronically ovariectomized female rhesus monkeys. Integrated plasma samples were collected at 20 min intervals for 3 hr before and 6 hr after nasogastric intubation of alcohol or isocaloric sucrose control solution. Baseline levels of LH and FSH were significantly higher in recently than in chronically ovariectomized females ( p<0.001). Baseline LH pulse frequency was also significantly higher ( p<0.001) in the recently ovariectomized group than in the chronically ovariectomized group (0.704±0.03 vs. 0.379±0.10 pulses/hr). FSH pulse frequency was equivalent in both groups (0.444±0.06 to 0.360±0.06 pulses/hr). After 2.5 g/kg of alcohol, peak blood alcohol levels were 243 to 256 mg/dl and LH decreased significantly ( p<0.01) in both groups. After 3.0 g/kg alcohol, peak blood alcohol levels were 237 to 289 mg/dl, and basal LH levels ( p<0.05) and LH pulse frequency ( p<0.05) decreased significantly only in the recently ovariectomized group. After 3.5 g/kg of alcohol, peak blood alcohol levels exceeded 320 mg/dl, and LH did not change significantly in either group. Administration of 3.5 g/kg alcohol was associated with increased LH pulse amplitude in some individuals. Since lower alcohol doses (2.5 and 3.0 g/kg) and sucrose control administration were followed by a significant decline in LH ( p<0.05−0.01) and the highest alcohol dose (3.5 g/kg) was not, these data suggest the possible influence of nonspecific “stress” on modulation of LH secretory activity. FSH did not change after sucrose administration in recently ovariectomized monkeys, but was significantly suppressed after 2.5 and 3.5 g/kg alcohol ( p<0.05). In the chronically ovariectomized monkeys, FSH decreased significantly after administration of sucrose and all alcohol doses. LH suppression was not consistently associated with changes in FSH in either group—a finding consonant with the hypothesis that LH and FSH may be controlled by different hypothalamic regulatory factors.

Effect of ethanol on androgen receptors in the anterior pituitary, hypothalamus and brain cortex in rats

The purpose of this study was to investigate ethanol-induced changes in androgen receptor sites in the anterior pituitary, hypothalamus, and brain cortex. Young adult male King-Holtzman rats were fed for 5 months a nutritionally complete liquid diet, with ethanol or isocaloric sucrose constituting 36% of the total calories. Androgen receptor sites were measured by sucrose density gradient and charcoal assay using tritiated dihydrotestosterone (DHT). Scatchard plot analysis of the data revealed that apparent dissociation constants of DHT-receptor complex for the anterior pituitary, hypothalamus, and brain cortex from alcohol-fed animals were estimated to be 0.7 ± 0.13, 0.6 ± 0.16 and 0.9 ± 0.15 nM, respectively. These values are identical to those of their isocaloric controls. The concentrations of cytosol androgen receptors of the pituitary, hypothalamus, and brain cortex from alcohol-fed rats were 8.0 ± 1.2, 6.2 ± 1.0 and 4.9 ± 0.7 fmol/mg protein, respectively. This represents about a 34, 24, and 22% reduction when compared to the values of the isocaloric control animals. In contrast to control rats, neither castration nor androgen or LHRH replacement to castrated alcohol-fed rats altered an alcohol-induced reduction of androgen receptor contents. Serum LH and testosterone levels were significantly decreased in alcohol-fed rats but these hormone levels were increased by administration of LHRH or norepinephrine. Such reduction of androgen receptors, serum LH and testosterone, but enhancement of these hormone levels by treatment with neurohormone and neurotransmitter in these animals suggests that ethanol exerts an adverse effect on the hypothalamic-pituitary unit and the neurotransmitter-hypothalamic hormone relationship, resulting in impairment of the androgen-induced sexual events and a suppression of the pituitary gonadotropin secretion.

Folate deficiency and acute ethanol treatment on pregnancy outcome in the rat

The interaction of folate deficiency and acute ethanol (EtOH) treatment on tissue folate level and fetal outcome was investigated. Sprague-Dawley rats (50-d-old) were fed folate deficient (no folic acid added) or folate sufficient (2 mg folic acid/kg) diet containing 1% succinylsulfathiazole for 7 weeks prior to and during gestation. On day 11 EtOH was administered intragastrically to half of the deficient and sufficient rats (5g/kg in 2 divided doses 4 hrs apart). Other halves served as controls were given isocaloric sucrose in the same manner. Rats were killed on day 21; pregnancy outcome and tissue folate levels were examined. Total folate values in maternal plasma and liver and placenta as well as in fetal liver and brain were all reduced in deficient groups. EtOH treatment had no effect on tissue folate level. Although food intakes were not different among groups throughout the experiment, maternal weight gains during gestation differed. Deficient groups gained much less, had more dead and resorbed fetuses and smaller live fetuses. Between the two deficient groups, EtOH treated rats produced three times more dead and resorbed fetuses than folate deficient alone. On the contrary, in folate sufficient groups EtOH had no effect on pregnancy outcome. It is concluded that under poor folate nutrition even a moderate EtOH given at a critical period of fetal development can severely impair fetal development.

Role of alcohol-induced hypothermia in mediating the teratogenic effects of alcohol in C57BL/6J mice.

The purpose of this study was to determine the role of alcohol-induced maternal hypothermia in the teratogenic actions of alcohol. C57BL/6J mice were administered an acute dose of alcohol (5.8 g/kg orally) or isocaloric sucrose on day 10 of gestation. One half of each group was placed for 6 hr in an incubator set at 32 degrees C and the other half was housed in the incubator at room temperature (22 degrees C). As expected, acute prenatal alcohol exposure at this time of gestation was associated with decreased birth weight and an increase in limb and kidney malformations. The significant alcohol x environmental temperature interaction on these dependent variables indicated that the teratogenic insult was not attenuated, but was in fact even greater for the 32 degrees C/alcohol group. An absence of a main effect of environmental temperature indicated that the 32 degrees C environment, per se, was not teratogenic. Thus, maternal hypothermia is probably not an etiological factor in animal models of fetal alcohol syndrome. Moreover, antagonism of alcohol-induced maternal hypothermia exacerbates the teratogenic actions of alcohol observed at room temperature.

Pharmacokinetics of ethanol in the guinea pig.

Chronic consumption of ethanol by pregnant and nonpregnant guinea pigs for 8 weeks at doses of 1.2 or 1.6 g/kg body weight twice daily affected pregnancy outcome and changed the pharmacokinetics of ethanol elimination. Ethanol treatment as compared to that of isocaloric sucrose decreased maternal weight, and decreased both the litter size and the number of liveborn offspring. Total litter weight was significantly decreased with the low ethanol dose (12% alcohol-derived energy). During pregnancy, low and high doses produced peak blood ethanol concentrations (BEC) of 89 +/- 8 mg/dl (mean +/- SE) and 125 +/- 6 mg/dl, respectively. At the high dose, peak BEC decreased dramatically (about 30%) in both pregnant and nonpregnant animals from treatment weeks 0 to 4; thereafter peak BEC remained depressed up to 8 weeks of treatment, which occurred with a concomitant increased volume of ethanol distribution. With both doses, rates of ethanol elimination and Michaelis-Menten's Vm values were significantly lower among pregnant as compared with nonpregnant guinea pigs during 8 weeks of treatment. These data suggest that the guinea pigs can be a valuable animal model to study the effects of low ethanol doses on fetal growth, the adaptation of peak BEC with duration of treatment and the lower rate of ethanol elimination in pregnancy.

Maternal age as a factor in determining the reproductive and behavioral outcome of rats prenatally exposed to ethanol

Nulliparous Long-Evans rats were bred at one of four different ages and assigned to one of three treatment groups within each age condition. Maternal ages were 9, 18, 32, and 36 weeks. Treatment groups were ethanol (E), administered by gavage as 8 g/kg in two divided doses on days 10–14 of gestation, pair-fed (PF) controls, administered as an isocaloric sucrose solution by gavage on days 10–14 of gestation, and ad lib fed controls (C). All offspring were surrogate fostered shortly after delivery to untreated recently parturient dams. Litter sizes were standardized to 8 on the day of birth. Offspring were assessed longitudinally for growth, mortality, and behavior (olfaction, locomotor activity, maze learning, avoidance acquisition and startle). Approximately 85% of the 36 week old dams did not produce viable litters. In the remaining maternal age conditions, ethanol delayed offspring olfactory orientation and increased locomotor activity, the latter dissipating after 50–60 days of age. These ethanol-related effects occurred independent of maternal age condition. Maternal age, independent of ethanol, was a factor which reduced litter size and offspring weight up to 50 days, but produced few effects on behavior. The combination of maternal age and prenatal ethanol interacted to increase pregnancy loss (oldest maternal age), reduce offspring weight up to day 99 (oldest and middle maternal age), alter olfactory orientation performance (oldest and middle maternal age), reverse the typical ethanol-induced increase in activity for males in the figure-8 test (oldest maternal age group), shift the pattern of open-field activity, and change errors in a complex water maze. Not all of these interactions turned out to be specific to the ethanol × old maternal age condition. Several of the interactions occurred in both the old and middle maternal age conditions. The only effect of old maternal age that interacted strongly with ethanol was in their combined effects on reproduction. Here the combination of the two factors increased maternal mortality, the number of early pregnancy losses, and the number of litters where all members were dead or resorbed. It was concluded that short-term prenatal ethanol combined with advanced maternal age produces additive interactions on pregnancy success without affecting longer-term outcomes, while young maternal age showed no clear detrimental effects compared to the middle maternal age reference group.

Effect of prenatal exposure to ethanol on body growth and the pituitary beta-endorphin.

Pregnant rats were fed an ethanol diet from the first day of pregnancy until parturition. Control rats were either pair fed with an isocaloric sucrose diet, or fed with standard lab chow (basic control group). Rats fed with the ethanol diet and their pair-fed controls showed a similar increase in body weight during pregnancy, which was lower than the increase observed in the basic control group. At 10 days after ethanol withdrawal all three groups presented similar body weights. A lower body growth was exhibited by the offspring of both the ethanol and the sucrose pair-fed rats, implicating a prenatal nutritional factor on the postnatal growth. Furthermore, the rate of body growth was lower in the offspring of the ethanol-treated animals than in the offspring of both their pair-fed and the basic control rats, indicating the presence of an additional ethanol-associated factor. On day 4 of development, the concentration of beta-endorphin peptides (pmol/mg protein) in the pituitary gland and the anterior lobe, of the offspring of the ethanol-treated animals and their sucrose pair-fed controls, was significantly higher than that of the offspring of the basic control animals. However, a lower content of beta-endorphin-like peptides was noticed in the whole pituitary gland, the anterior lobe, and the intermediate lobe of the offspring of the ethanol-treated rats and their pair-fed controls on days 8, 14, and 22 postnatally.(ABSTRACT TRUNCATED AT 250 WORDS)

Prenatal alcohol exposure shortens life span in rats.

In a study of the effects of in utero alcohol exposure on life span in rats, pregnant rats were intubated twice daily with 3.5 gm/kg alcohol on gestational days 11-21 or with an isocaloric sucrose solution. These latter animals were pair-fed and pair-watered to alcohol-treated animals. A third group served as nontreated ad lib-fed controls. At birth, all offspring were removed from their biological mothers, culled to eight per litter, and placed with nontreated surrogate dams. Alcohol-exposed animals died at a significantly younger age than pair-fed and ad lib controls and never attained the same maximum body weights as control animals. For females prenatally exposed to alcohol, life span was shortened by about 20 weeks; in male cohorts, life span was shortened by about 2.5-7 weeks.

Effect of indomethacin on alcohol-induced morphological anomalies in mice

The purpose of the present study was 1) to examine the effect of indomethacin (INDO), a prostaglandin synthesis inhibitor, on alcohol-induced growth and morphological impairment in C57BL/6J mice (Study 1) and 2) to determine if INDO crosses the placenta (Study 2). On day 10 of gestation, mice were injected (s.c.) acutely with either 0, 5, 10, or 20 mg/kg INDO, followed one hour later by alcohol (5.8 g/kg orally) or isocaloric sucrose. Fetuses were removed on day 19 of pregnancy, weighed, and examined for anomalous development. As expected, Study 1 demonstrated that maternal alcohol treatment decreased fetal weight and increased the number of fetuses with birth defects. INDO alone decreased fetal weight but did not affect morphologic development. More importantly, INDO antagonized alcohol-induced birth defects, but only at the highest dose. The results of Study 2 suggest that the relative ineffectiveness of INDO may be related to its inability to readily cross the placenta. Since high doses of INDO also caused maternal toxicity, the usefulness of this compound in future studies of this type was questioned.

Delayed pubertal development of the male reproductive tract associated with chronic ethanol ingestion

Little is known concerning the sensitivity of the reproductive tract to ethanol as a function of development. The present study was conducted to evaluate the action of chronic ethanol ingestion on sexual maturation of the male. Mice were given free access to liquid diets containing 5% (v/v) ethanol for either 29 or 43 days, starting at age 20 days. Controls were given liquid diets in which isocaloric sucrose replaced the ethanol. Daily diet consumption and peak blood ethanol levels were highest during the first 2 weeks of treatment, dropping thereafter to adult levels of approximately 680 ml/kg body weight and 160 mg/dl respectively. Plasma testosterone levels were depressed by ethanol throughout treatment, the reduction being somewhat greater when measured during week 6 of treatment (average = 74% inhibition) as compared to either week 2 (36%) or week 4 (25%). Average weights of testes, epididymides and seminal vesicles were depressed by 24% (P < 0.002), 16% (P < 0.005) and 13% (NS), respectively, after 29 days. Testicular development was also impaired in ethanol-treated animals after 29 days. Tunica albuginea thickness and seminiferous tubule diameter were decreased (by 31%, P < 0.05; and 16%, P < 0.01 respectively), whereas desquamation of immature germ cells and inactive tubules were increased (325 and 780% respectively; P < 0.01). Quality of spermatogenesis was poorer in ethanol-treated animals (P <0.05). Also observed were decreased sperm motility (62% inhibition, P < 0.01) and capacity to fertilize (decreased by 67%, P < 0.01), and an increase in the incidence of morphologically abnormal spermatozoa (by 163%, P < 0.001). Semen volume was lower (reduced by 57%, P = 0.05), as was the total number of motile ejaculated spermatozoa (reduced by 81%, P < 0.05). After 43 days treatment, improvement was noted in all indices of fertility except for the number of motile ejaculated spermatozoa. Significant differences persisted only for dysmorphic spermatozoa and volume and sperm count of electroejaculated semen. These data suggest that ethanol ingestion during pubertal development can delay several aspects of sexual maturation in the male.

Mechanisms underlying the differential effects of ethanol on the bioavailability of riboflavin and flavin adenine dinucleotide.

Chronic alcoholism is associated with a high prevalence of riboflavin deficiency. Experiments were designed in an animal model to determine whether ethanol alters selectively the absorption of riboflavin and flavin adenine dinucleotide (FAD), the predominant dietary form of the vitamin. Rats received by gavage a liver homogenate to which either [14C]riboflavin or [14C]FAD was added with either ethanol or isocaloric sucrose solutions. Ethanol markedly diminished the bioavailability of [14C]FAD to a greater degree than that of [14C]riboflavin. Corroboration of an ethanol-impaired intraluminal hydrolysis of FAD was provided by using everted jejunal segments and measuring mucosal uptake of [14C]riboflavin together with nonradiolabeled FAD. In subsequent studies with mucosal cell extracts, ethanol markedly inhibited activities of FAD pyrophosphatase and flavin mononucleotide (FMN) phosphatase. These findings suggest that dietary sources of riboflavin (FMN and FAD) are not absorbed as well in the presence of ethanol than are vitamin preparations containing riboflavin, which is utilized more readily.

Sucrose substitution in prevention and reversal of the fall in metabolic rate accompanying hypocaloric diets

Hypocaloric diets cause a fall in resting metabolic rate that interferes with weight loss. To evaluate the mechanisms underlying this phenomenon, resting metabolic rate was measured sequentially in six healthy obese women on a weight maintenance diet (more than 2,300 kilocalories), after 15 days of an 800 kilocalories carbohydrate-free diet, and after isocaloric sucrose replacement for an additional 15 days. The carbohydrate-free diet produced a 21 percent decline in resting metabolic rate (p <0.005) as well as a decrease in circulating triiodothyronine (41 percent, p <0.02) and insulin (38 percent, p <0.005) concentrations. Plasma norepinephrine levels also tended to decline (10 percent, 0.05> p <0.1). However, when sucrose was substituted, resting metabolic rate rose toward baseline values even though total caloric intake was unchanged and weight loss continued. The sucrose-induced rise in resting metabolic rate was accompanied by a rise in serum triiodothyronine values, but not plasma insulin or norepinephrine concentrations. Throughout, changes in resting metabolic rate correlated with changes in serum triiodothyronine levels (r = 0.701, p <0.01). In four obese women, a hypocaloric sucrose diet was given at the outset for 15 days. The fall in both resting metabolic rate and triiodothyronine concentration was markedly reduced as compared with values during the carbohydrate-free diet. It is concluded that carbohydrate restriction plays an important role in mediating the fall in resting metabolic rate during hypocaloric feeding. This effect may, at least in part, be related to changes in circulating triiodothyronine levels. Incorporation of carbohydrate in diet regimens may, therefore, minimize the thermic adaptation to weight loss.

Effects of prenatal alcohol exposure on behavior of aged rats

Pregnant rats were intubated with alcohol (3.5 g/kg, twice daily) on gestation days 11–21. Control animals were intubated with an isocaloric sucrose solution and were pair-fed and pair-watered to alcohol-treated dams. At birth, offspring were placed with non-treated surrogate dams. When animals were slightly more than 1 year of age, they were tested for passive avoidance learning, spontaneous alternation and activity. Groups did not differ in passive avoidance learning or spontaneous alteration but animals prenatally exposed to alcohol were more active than controls. Additional studies showed that this increased activity was not affected by testing animals in the presence of environmental stimuli such as objects which could be manipulated, or by odors from mouse shavings from male and female mice.

Dietary Regulation of Intestinal Lactase and Sucrase in Adult Rats

To characterize the mechanisms leading to dietary evoked increases of lactase and sucrase activities by carbohydrates, we performed a quantitative comparison of the effects of lactose and sucrose on the corresponding disaccharidases in the jejunum of 2‐month‐old rats. For. 7–10 days the rats were fed a low‐starch (5 cal%), high‐fat (73 cal%) diet, and for various periods of time (3–72 h) were given an isocaloric sucrose or lactose (20, 40, or 70 cal%) diet. Lactase and sucrase activities in jejunal homogenates were significantly increased within 3 h after the initial feeding of the sucrose (40 cal%) diet. After 3 h of feeding the sucrose diet, sucrase activity gradually increased and reached its maximum at 24 h, whereas lactase activity did not exhibit further change. Increased intake of sucrose led to an increase of lactase and sucrase activity. Within a range of doses of digestible amounts of lactose, the effect of diet containing lactose on these disaccharidase activities was similar to the effect of the diet containing sucrose. This similarity suggests the important role of the common constituent sugar, i.e., glucose. Further, analyses of response to these disaccharides along the villus‐crypt axis revealed that the increase of lactase activity occurs at a more apical and broader locus of cohort of epithelial cells along the height of the villus than that of sucrase, suggesting that different mechanisms are involved in dietary regulation of lactase and sucrase.

Combined effects of moderate ethanol consumption and a low-protein diet during gestation on brain development in [formula omitted] mice

We investigated whether or not moderate ethanol consumption during gestation would interact with the effects of a low-protein diet in affecting brain development in BALB c mice. The independent variables included fetal body and brain weights and cross-sectional area in midsagittal sections of the corpus callosum (CC) and anterior commissure (CA). Pregnant animals were fed either ethanol 12% v/v or an isocaloric sucrose solution from days 5 to 19 of gestation, when fetal development was assessed. In addition, the animals were fed semisynthetic isocaloric diets containing either 8 or 20% casein. All animals were pair-fed to those in the group receiving ethanol and 20% casein; an additional control group was fed lab chow ad libitum. There was clearly an interactive effect of diet and ethanol consumption on blood alcohol concentrations: those in the low-protein group were significantly higher than in the normal-protein group. Similarly, the effect on body weight in the group receiving low protein plus ethanol was greater than the additive effect of either treatment alone, although this may have been due partly to differences in litter size. Brain weight in this group was also significantly less than in the other three groups, which did not differ from each other. Covariance analysis, adjusting brain weight for body weight, suggested a brain-sparing effect of low protein but not ethanol. Neither treatment affected the incidence of the CC being absent at midline. The low-protein treatment decreased the cross-sectional area of both the CC and CA; the effect on the CC was independent of brain weight. There was no effect of ethanol on either of those measures.

Hyperuricemia and hypertriglyceridemia: Metabolic basis for the association

Hypertriglyceridemia has been reported frequently in patients with hyperuricemia and gout. The current studies have evaluated this relationship. To examine whether hypertriglyceridemia leads to hyperuricemia, IV Intralipid was given to three gouty patients. Triglycerides increased from 169 to 700 mg/dl for three hours but caused no change in serum urate level or urine uric acid and oxypurine excretion. We next examined whether high carbohydrate intake increases serum urate and triglyceride levels. Four obese patients were placed on a 2000 kcal/d sucrose diet for seven days. The serum urate increased from 6.3 ± 1.7 to 7.9 ± 2.0 mg/dL. The percent uric acid clearance to creatinine clearance decreased from 5.9 ± 1.3 to the lowest mean value of 3.7 ± 1.2, while serum triglycerides increased from 106 ± 33 to 252 ± 57 mg/dL and blood lactate from 607 ± 227 to 1167 ± 381 μmol/L. A 3000 kcal/d glucose diet in four other obese subjects produced no change in serum urate levels but increased lactate and triglyceride levels. During an isocaloric sucrose diet in two normal men, the serum urate level increased from 5.3 and 4.0 to peak values of 9.5 and 7.4 mg/dL. The percent uric acid to creatinine clearance decreased from 5.6 and 6.6 to 2.9 and 3.3. The uric acid turnover did not increase. In three gouty patients the mean serum urate increased from 8.5 ± 1.5 to 10.6 ± 1.4 mg/dL following an isocaloric sucrose diet. The urine uric acid excretion increased from 0.30 and 0.25 to 0.37 and 0.38 mg/mg creatinine in two patients. The percent uric acid clearance to creatinine clearance decreased from 3.8 to 2.5 in one patient. The serum triglycerides were substantially elevated during the sucrose diet in the normal subjects and the gouty patients. Our studies show that a pure sucrose diet increases both the serum urate and triglyceride levels. The mechanism of the hyperuricemia is decreased renal clearance of uric acid in the obese normal controls and the normal subjects. Increased urate production and decreased uric acid clearance accounted for the hyperuricemia in the gouty patients. The contribution of excessive sucrose ingestion to clinically associated hyperuricemia and hypertriglyceridemia remains to be elucidated.

Enhancement of hepatocellular genotoxicity of several mutagens from amino acid pyrolysates and broiled foods following ethanol pretreatment

The effect of subchronic ethanol ingestion on the genotoxicity and metabolism of the mutagens 3-amino-1,4-dimethyl-5 H-pyrido[4,3- b]indole (Trp-P-1), 3-amino-1-methyl-5 H-pyrido[4,5- b]indole (Trp-P-2), 2-amino-6-methyldipyrido[1,2- a:3′,2′- d]imidazole (Glu-P-1), 2-aminodipyrido[1,2- a:3′,2′- d]imidazole (Glu-P-2), 2-amino-3-methylimidazo[4,5- f]quinoline (IQ) and 2-amino-3,4-dimethylimidazo[4,5- f]quinoline (MeIQ) was evaluated in primary cultures of rat hepatocytes. Male Sprague-Dawley rats were pair-fed, for 8 days, liquid diets containing either ethanol (8%, v/v) or an isocaloric sucrose solution. Ethanol pretreatment significantly ( P < 0.05, Student's t test) enhanced the level of DNA repair stimulated by Glu-P-1, Glu-P-2, IQ and MeIQ. Statistically significant increases in DNA-repair activity ranged from 1.9-fold for IQ to 3.4-fold for Glu-P-2. Following a 16-hr exposure, the concentration of parent mutagen in the culture medium decreased by 75–98%. Neither the rate of mutagen metabolism in hepatocyte cultures nor the extent of mutagenic activation in microsome preparations was appreciably affected by ethanol pretreatment. The results suggest that ethanol pretreatment enhances the genotoxicity of Glu-P-1, Glu-P-2, IQ and MeIQ by inducing non-microsomal activation processes.

Effect of moderate prenatal ethanol exposure on postnatal brain and behavioral development in [formula omitted] mice

Prior research had indicated that moderate maternal ethanol consumption during gestation affected the growth of the corpus callosum and anterior commissure in BALB c mice when measured at day 19 postconception. Our purpose was to assess whether or not this was an enduring effect. Pregnant BALB cCRBL mice were fed ethanol 10% v v in the drinking water from days 5 to 26 postconception. Control animals received an isocaloric sucrose solution and were pair-fed to the experimental animals. An additional control group fed laboratory chow ad libitum was included. Using a split-litter design, brain development was assessed on days 26 and 50 postconception and behavioral development of the pups was measured on day 32. The ethanol-treated offspring had lower brain weights at both ages as well as a smaller cross-sectional area of the anterior commissure on day 50, which was significantly related to the smaller brain weight. There was no apparent effect of ethanol on the area of the corpus callosum at either age. Similarly, behavioral development was not affected by the treatment, although eye-opening was delayed in ethanol-treated animals. Measures of maternal behavior indicated that the animals consuming alcohol were more active than those in the control groups. An unexpected finding was that the control group fed sucrose appeared to be adversely affected. The body weight of these pups was lower, as was the area of the corpus callosum at day 50.