Iron supplementation does not aggravate impaired glucose tolerance and sugar overload-induced genotoxicity in rats.

High sugar intake is a major risk factor for metabolic disorders. Genotoxicity is an important factor in diabetes onset, and iron (Fe) may be an aggravating element. However, this relationship is still poorly established. Thus, this study evaluated whether Fe supplementation could aggravate obesity, impaired glucose tolerance, and sugar overload-induced genotoxicity in rats. A total of 24 rats were treated with different diets: standard diet (SD, n = 8), invert sugar overload (320 g/L, HSD, n = 8), or Fe plus invert sugar overload (2.56 mg/L of Fe2+, Fe-HSD, n = 8) for four months. After treatment, the Fe-HSD group showed no excessive weight gain or impaired glucose tolerance. DNA damage in blood, as assessed by comet assay, gradually increased in HSD during treatment (p < 0.001), whereas Fe-HSD showed a nonlinear increase in DNA damage. Moreover, Fe-HSD presented 0.6-fold more DNA damage compared with SD (p = 0.0055) in the 1st month of treatment. At months 2 and 3, results show a ≥ 1.4-fold increase in HSD and Fe-HSD DNA damage, respectively, compared with SD (p < 0.01). At the end of the experiment, only HSD DNA damage differed from SD (1.5-fold more, p = 0.0196). Fe supplementation did not aggravate the invert sugar-induced DNA damage (p > 0.05). In the pancreas, results showed no differences in DNA damage. Mutagenicity, evaluated by micronucleus testing, was not observed regardless of treatment (p = 0.428). Fe supplementation, in the evaluated concentration, did not aggravate weight gain, impaired glucose tolerance, and sugar overload-induced genotoxicity in rats.

Effects of different maternal diets on adipose tissue inflammation and liver tissue oxidative stress in dams and their female offspring.

Pregnancy and lactation are important stages of fetal development. Therefore, this study investigated how different maternal diets offered during gestation and lactation periods affect adipose tissue inflammation and liver tissue oxidative stress of dams and their female offspring. Female BALB/c albino mice (60 days old) were randomized into three groups receiving a standard (CONT), hypercaloric (HD), or restricted (RD) diet during the pregnancy. After birth, female offspring weaned at 21 days were divided into two groups that received a standard or restricted diet (CONT/CONT, CONT/RD, RD/CONT, RD/RD, HD/CONT, and HD/RD) until 100 days old. Histological, oxidative parameters and inflammatory infiltrate of dams' and offspring's liver and adipose tissue were evaluated. HD dams presented non-alcoholic steatohepatitis (NASH) diagnosis and an increase in tumor necrosis factor-alpha (TNF-α) concentrations when compared to the RD and CONT dams, indicating a pro-inflammatory state. High concentrations of malondialdehyde (MDA) formation and catalase (CAT) activity in HD when compared to the CONT in the liver. SOD activity decreased in RD mice compared to CONT, and the SOD/CAT ratio was decreased in the RD and HD in comparison to the CONT. The maternal diet leads to an increase in SOD in RD/RD compared to HD/RD. RD-fed dams showed an increase in inflammatory infiltrates compared to CONT, evidencing changes caused by a restrictive diet. In the HD/CONT offspring, we verified an increase in inflammatory infiltrates in relation to the offspring fed a standard diet. In conclusion, HD, and RD, during pregnancy and lactation, altered the liver and adipose tissues of mothers. Furthermore, the maternal diet negatively impacts the offspring's adipose tissue but does not cause liver damage in these animals in adult life.

The G protein-coupled estrogen receptor (GPER) regulates recognition and aversively-motivated memory in male rats.

Estrogens, particularly 17ß-estradiol (estradiol, E2), regulate memory formation. E2 acts through its intracellular receptors, estrogen receptors (ER) ERα and ERß, as well as a recently identified G protein-coupled estrogen receptor (GPER). Although the effects of E2 on memory have been investigated, studies examining the effects of GPER stimulation are scarce. Selective GPER agonism improves memory in ovariectomized female rats, but little information is available regarding the effects of GPER stimulation in male rodents. The aim of the present study was to investigate the effects of the GPER agonist, G1, on consolidation and reconsolidation of inhibitory avoidance (IA) and object recognition (OR) memory in male rats. Animals received vehicle, G1 (15, 75, 150 µg/kg; i.p.), or the GPER antagonist G15 (100 µg/kg; i.p.) immediately after training, or G1 (150 µg/kg; i.p.) 3 or 6 h after training. To investigate reconsolidation, G1 was administered immediately after IA retention Test 1. Results indicated that G1 administered immediately after training at the highest dose enhanced both OR and IA memory consolidation, while GPER blockade immediately after training impaired OR. No effects of GPER stimulation were observed when G1 was given 3 or 6 h after training or after Test 1. The present findings provide evidence that GPER is involved in the early stages of memory consolidation in both neutral and emotional memory tasks in male adult rats.

Liver and kidney function markers among gym users: the role of dietary supplement usage.

Dietary supplements have been increasingly used by gym users and are often consumed without the guidance of a health professional. Moreover, the indiscriminate supplements use can have adverse health effects, such as changes in liver and kidney function. The aim of this study was to verify the association between dietary supplements intake with alterations in the liver and kidney function among gym users. A cross-sectional study was conducted with 594 gym users (mean age 37 (sd 14) years, 55·2 % women) from a city in southern Brazil. A questionnaire was used to evaluate the use of dietary supplements. The markers of the liver (alanine aminotransferase, aspartate aminotransferase (AST), alkaline phosphatase, γ-glutamyltransferase) and renal (creatinine and urea) function were also evaluated on a subsample of the study population. Data were analysed by binary logistic regression, adjusted for sex, age and education. The prevalence of dietary supplement intake was 36·0 %. Individuals who intake dietary supplements showed a higher prevalence to present slight alterations in the AST enzyme and in the urea after adjustments for potential confounders. In conclusion, the use of dietary supplement was associated with slight alterations in AST enzyme and in the urea among gym users. These findings show the importance of using supplements correctly, especially with guidance from professionals trained to avoid possible risks to health.

Effects of lipoic acid supplementation on age- and iron-induced memory impairment, mitochondrial DNA damage and antioxidant responses.

PURPOSE: To investigate the effects of lipoic acid (LA) supplementation during adulthood combined with supplementation later in life or LA administration only at old age on age-induced cognitive dysfunction, mitochondrial DNA deletions, caspase 3 and antioxidant response enzymes expression in iron-treated rats. METHODS: Male rats were submitted to iron treatment (30 mg/kg body wt of Carbonyl iron) from 12 to 14th post-natal days. Iron-treated rats received LA supplementation (50 mg/kg, daily) in adulthood and old age or at old age only for 21 days. Memory, mitochondrial DNA (mtDNA) complex I deletions, caspase 3 mRNA expression and antioxidant response enzymes mRNA expression were analyzed in the hippocampus. RESULTS: LA administration in adulthood combined with treatment later in life was able to reverse age-induced effects on object recognition and inhibitory avoidance memory, as well as on mtDNA deletions, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) expression, and antioxidant enzymes disruption induced by iron in aged rats. LA treatment only at old age reversed iron-induced effects to a lesser extent when compared to the combined treatment. CONCLUSION: The present findings support the view that LA supplementation may be considered as an adjuvant against mitochondrial damage and cognitive decline related to aging and neurodegenerative disorders.

Invert sugar induces glucose intolerance but does not cause injury to the pancreas nor permanent DNA damage in rats.

The high consumption of sugars is linked to the intermediate hyperglycemia and impaired glucose tolerance associated with obesity, inducing the prediabetes. However, the consequences of excessive invert sugar intake on glucose metabolism and genomic stability were poorly studied. The aim of this study was to evaluate the effects of invert sugar overload (32%) in rats, analyzing changes in obesity, glucose tolerance, pancreatic/hepatic histology and primary and permanent DNA damage. After 17 weeks, the rats became obese and had an excessive abdominal fat, as well as presented impaired glucose tolerance, caused by higher sugar caloric intake. Primary DNA damage, evaluated by the comet assay, was increased in the blood, however not in the pancreas. No protein carbonylation was seen in serum. Moreover, no increase in permanent DNA damage was seen in the bone marrow, evaluated using the micronucleus test. Some rats presented liver steatosis and that the pancreatic islets were enlarged, but not significantly. In this study, invert sugar altered the glucose metabolism and induced primary DNA damage in blood, but did not cause significant damage to the pancreas or liver, and neither changes in the levels of oxidative stress or permanent DNA damage.

Influence of hesperidin and vitamin C on glycemic parameters, lipid profile, and DNA damage in rats treated with sucrose overload.

We evaluated the influence of hesperidin and vitamin C (VitC) on glycemic parameters, lipid profile, and DNA damage in male Wistar rats treated with sucrose overload. Rats were divided into six experimental groups: I-water control; II-sucrose control; III-hesperidin control; IV-VitC control; V-co-treatment of sucrose plus hesperidin; VI-co-treatment of sucrose plus VitC. We measured the levels of triglycerides, total cholesterol, HDL-c, LDL-c, fasting glucose, and glycated hemoglobin (A1C). DNA damage was evaluated in blood and brain cells using the comet assay and the micronucleus test was used to evaluate chromosomal damages in the rat bone marrow. Co-treatment with VitC, but not with hesperidin, normalized the serum glucose. No effect of co-treatments was observed on A1C. The co-treatment with VitC or hesperidin did not influence the lipid profile (p>0.05). Rats co-treated with hesperidin had a significantly lower DNA damage level in blood (p<0.05) and brain (p<0.05). Rats treated with VitC only, but not those co-treated with VitC plus sucrose, had significantly higher DNA damage in brain (p<0.05). No significant differences were observed in the results of micronucleus test (p>0.05). Hesperidin and VitC showed different effects on sucrose and DNA damage levels. While VitC lowered the serum glucose, hesperidin reduced the DNA damage.

High consumption of sucrose induces DNA damage in male Wistar rats.

The purpose of this study was to determine the effects of the high consumption of sucrose on the levels of DNA damage in blood, hippocampus and bone marrow of rats. Male Wistar rats were treated for 4 months with sucrose (10% for 60 initial days and 34% for the following 60 days) in drinking water, and then, glycemia and glycated hemoglobin (A1C) were measured. Levels of DNA damage in blood and hippocampus were evaluated by the comet assay. The micronucleus test was used to evaluate chromosomal damages in the bone marrow. The sucrose treatment significantly increased (p<0.01) the serum glucose levels (~20%) and A1C (~60%). The level of primary DNA damage was significantly increased (p<0.05) in hippocampal cells (~60%) but not in peripheral blood leukocytes (p>0.05). Additionally, it was observed a significative increase (p<0.05) in the markers of chromosomal breaks/losses in bone marrow, as indicated by the micronucleus test. This is the first study that evaluated DNA damage induced by high sucrose concentration in the hippocampus and bone marrow of rats. Sucrose-induced DNA damage was observed in both tissues. However, the mechanism of sucrose toxicity on DNA remains unknown.

Recognition memory and DNA damage in undernourished young rats.

This study evaluated the recognition memory and the levels of DNA damage (blood and hippocampus) in undernourished young Wistar rats. The experiment was conducted along 14-week with rodents divided in control group (CG, n=8) and undernourished group (UG, n=12) which was submitted to caloric restriction. Nutritional status for undernutrition was defined by Body Mass Index (BMI) ≤0.45g/cm2 and by weighting the organs/tissue (liver, spleen, intestine, peritoneal fat, kidney and encephalon). The Novel Object Recognition Test assessed recognition memory and the Comet Assay evaluated the levels of DNA damage. Student t test, 2-way ANOVA and Pearson's correlation analysis were used and the significance level was of p<0.05. The UG showed lower BMI and organ/tissue weights than CG (p<0.001). In short-term memory, the recognition rate was higher in the UG (p<0.05), only after 4 weeks. In the long-term memory, again recognition rate was higher in the UG than the CG, after 4 weeks (p<0.001) and 14 weeks (p<0.01). The UG showed decreased levels of DNA damage in the blood (p<0.01) and increased levels in the hippocampus (p<0.01). We concluded in this study that the undernutrition by caloric restriction did not cause impairment in recognition memory, however induced DNA damage in the hippocampus.

Effects of the AMPAR Antagonist, Perampanel, on Cognitive Function in Rats Exposed to Neonatal Iron Overload.

Iron accumulation has been associated with the pathogenesis of neurodegenerative diseases and memory decline. As previously described by our research group, iron overload in the neonatal period induces persistent memory deficits and increases oxidative stress and apoptotic markers. The neuronal insult caused by iron excess generates an energetic imbalance that can alter glutamate concentrations and thus trigger excitotoxicity. Drugs that block glutamatergic receptor eligibly mitigate neurotoxicity; among them is perampanel (PER), a reversible AMPA receptor (AMPAR) antagonist. In the present study, we sought to investigate the neuroprotective effects of PER in rats subjected to iron overload in the neonatal period. Recognition and aversive memory were evaluated, AMPAR subunit phosphorylation, as well as the relative expression of genes such as GRIA1, GRIA2, DLG4, and CAC, which code proteins involved in AMPAR anchoring. Male rats received vehicle or carbonyl iron (30 mg/kg) from the 12th to the 14th postnatal day and were treated with vehicle or PER (2 mg/kg) for 21 days in adulthood. The excess of iron caused recognition memory deficits and impaired emotional memory, and PER was able to improve the rodents' memory. Iron increased the phosphorylation of GLUA1 subunit, which was reversed by PER. Furthermore, iron overload increased the expression of the GRIA1 gene and decreased the expression of the DLG4 gene, demonstrating the influence of metal accumulation on the metabolism of AMPAR. These results suggest that iron can interfere with AMPAR functionality, through altered phosphorylation of its subunits, and the expression of genes that code for proteins critically involved in the assembly and anchoring of AMPAR. The blockade of AMPAR with PER is capable of partially reversing the cognitive deficits caused by iron overload.

Effect of Probiotic Lacticaseibacillus rhamnosus LB1.5 on Anxiety-like Behavior, Neuroprotection and Neuroinflammation Markers of Male Mice Fed a High-Fat Diet.

Probiotic supplementation has been identified as a potential target to reduce inflammatory mediators associated with obesity. Therefore, this study assessed the effect of probiotic Lacticaseibacillus rhamnosus LB1.5 on anxiety-like behavior, gene expression in the prefrontal cortex, and neuroinflammation in the cerebral cortex and hippocampus of male mice fed a high-fat diet. Mice aged 21 days were divided into four groups: control (CONT), control plus probiotic (CONT + PROB), high-fat diet (HFD), and high-fat diet plus probiotic (HFD + PROB), and fed for 13 weeks. The probiotic Lact. rhamnosus 1.5 (3.1 × 108 CFU/mL, derived from raw buffalo milk) was administered by gavage three times a week. Probiotic supplementation provided an anxiolytic effect in CONT and HFD. The IL-6 showed lower levels after probiotic supplementation in the HFD. Regarding immunoreactivity for GFAP in the cerebral cortex, we demonstrated that animals HFD-fed had a reduction in cells number compared to CONT. In the hippocampus, we found an interaction between diet and supplementation, as well as an effect of probiotic supplementation. A higher number of Th positive cells was observed in the cerebral cortex in mice fed HFD. Lact. rhamnosus LB1.5 supplementation decreased serum IL-6 levels in HFD-fed mice and promoted a reduction in anxiety-like behavior.

DNA damage and cytotoxicity in adult subjects with prediabetes.

Prediabetes (intermediate hyperglycemia) is a high-risk state for diabetes that is defined by higher than normal glycemic levels that are below the level required for a diagnosis of diabetes. Prediabetes is characterized by oxidative stress, yet the associated DNA damage and cytotoxicity remain unknown to date. Therefore, we evaluated the relationship between glycemic alterations, DNA damage and cytotoxicity in the lymphocytes of individuals with pre-diabetes. Fasting plasma glucose (FPG) and glycated hemoglobin (A1C) levels were quantified and used as inclusion criteria. Anthropometric parameters were also evaluated. The cytokinesis-block micronucleus cytome assay (CBMN Cyt) was used to evaluate DNA damage and cytotoxicity. FPG correlated with A1C (r=0.562, p=0.002). Because A1C is the best predictor of diabetes complications, the association between A1C and the evaluated variables was assessed. The waist-hip ratio correlated with A1C (p<0.01). Regarding DNA damage, the frequency of nucleoplasmic bridges correlated with A1C (p<0.05). Both apoptosis and necrosis correlated with A1C (p<0.05). The overall frequency of DNA damage and cytotoxicity also correlated with A1C (p<0.01). Additional studies evaluating cell cycle and cell death patterns in prediabetes are necessary.

Influence of different categories of supplements on the body composition of resistance-training practitioners.

OBJECTIVE: The aim of this study was to investigate the influence of different categories of dietary supplements on the body composition of resistance-training practitioners. METHODS: Participants of both sexes and ages 20 to 59 y participated in this cross-sectional study. The use of dietary supplements was investigated and classified into three categories: sports foods, medical supplements, and ergogenic supplements. One-way analysis of covariance adjusted for age, type of exercise, frequency of exercise, total amount of daily exercise, and exercise intensity was used in the analysis. RESULTS: Of 427 participants, 278 (65%), were supplement consumers. Women who consumed sports foods had higher percentages of skeletal muscle (P = 0.014) and lower percentages of body fat than women who did not take supplements (P = 0.031). Furthermore, women who used medicinal supplements had greater visceral fat levels than women who did not (P = 0.019). No significant differences were found between type of supplement used and body composition among men (P > 0.05). CONCLUSIONS: Consuming sports foods was associated with higher percentages of skeletal muscle and lower percentages of body fat; women who used medical supplements had higher visceral fat levels.

Association between the use of muscle-building supplements and DNA damage in resistance training practitioners.

OBJECTIVES: Little is known about the relationship between the supplements used for sport and safety, especially regarding the induction of genotoxicity. Therefore, more knowledge about a DNA damage possibly caused using sport supplements is necessary. The aim of this study was to investigate the potential association between the use of muscle-building supplements and DNA damage in resistance training practitioners. METHODS: Muscle-building supplements were classified into three categories based on evidence of efficacy and safety: Strong Evidence to Support Efficacy and Apparently Safe (SESEAS); Limited or Mixed Evidence to Support Efficacy (LMESE), and Little to No Evidence to Support Efficacy and/or Safety (LNESES). DNA damage was evaluated by the comet assay (DNA damage index and frequency) and buccal micronucleus by the cytome assay (micronuclei and nuclear buds). In the sequence, the adjusted analysis of covariance was performed. This study included 307 individuals ages 37.99 ± 13.95 y (52.1% men), of which 157 consumed supplements. RESULTS: The results of the comet assay revealed that participants who used supplements had higher DNA damage indexes (P = 0.018) and damage frequency (P = 0.045) than those who reported using no supplements. Moreover, the comet assay also indicated that the participants who used supplements classified into the SESEAS category presented the highest DNA damage index (P = 0.025) and frequency (P = 0.044) compared with those who used no supplements. However, we found no significant difference in the micronuclei and nuclear buds in the evaluated groups (P > 0.05). CONCLUSION: Supplement use is not associated with permanent damage, suggesting that SESEAS supplements are safe for consumption.

A high-fat diet changes placental morphology but does not change biochemical parameters, placental oxidative stress or cytokine levels.

INTRODUCTION: The placenta is an organ that forms the bridge between mother and fetus during pregnancy. Changes in the intrauterine environment directly impact the fetus' health, with maternal nutrition determining its development. This study analyzed the effects of different diets and probiotic supplementation during pregnancy on the biochemical parameters of maternal serum and placental morphology, oxidative stress, and cytokine levels in mice. METHODS: Female mice were fed standard (CONT), restrictive (RD), or high-fat (HFD) diets before and during pregnancy. During pregnancy, the CONT and HFD groups were divided into two groups that received the Lactobacillus rhamnosus LB1.5 three times per week (CONT + PROB and HFD + PROB). The RD, CONT, or HFD groups received vehicle control. Maternal serum biochemical parameters (glucose, cholesterol, and triglycerides) were evaluated. The morphology, redox profile (thiobarbituric acid reactive substances, sulfhydryls, catalase, and superoxide dismutase enzyme activity), and inflammatory cytokines (interleukins 1α, 1ß, IL-6, and tumor necrosis factor-alpha) were evaluated in the placenta. RESULTS: The serum biochemical parameters presented no differences between the groups. Regarding placental morphology, the HFD group showed an increased thickness of the labyrinth zone compared to the CONT + PROB group. However, no significant difference was found in the analysis of the placental redox profile and cytokine levels. DISCUSSION: RD and HFD, for 16 weeks before and during pregnancy, as well as probiotic supplementation during pregnancy, caused no change in serum biochemical parameters nor the gestational viability rate, placental redox state, and cytokine levels. However, HFD increased the thickness of the placental labyrinth zone.

The moderating role of macronutrient intake in relation to body composition and genotoxicity: A study with gym users.

In a cross-sectional study of gymnasium users (both sexes, ages = 41.9 ± 14.8 years), we examined the moderating role of macronutrient intake in relation to body composition and genotoxicity. A questionnaire was administered to evaluate characteristics of the participants. To assess macronutrient consumption, we used 24-h food recalls on three non-consecutive days. Body composition (body fat percentage and muscle mass) was evaluated with a bioimpedance scale. Genotoxicity was assessed with the buccal micronucleus cytome assay. Multiple linear regression models were applied, adjusting for age; sex; tobacco and alcohol consumption; and (with regard to exercise habits) frequency, training time, intensity, and types. Micronucleus frequency was directly associated with body fat and inversely associated with muscle mass. Our study shows that carbohydrate and fat intakes affect body fat percentage and micronucleus frequency in gymnasium users.

Micronuclei frequency and renal function markers in gym members: The moderating role of supplement intake.

This research investigates the moderating role of dietary supplement intake in the relationship between MNi frequency and renal markers in gym members. A cross-sectional study was carried out with gym members of all sexes, between 20 and 59 years of age, with data on supplement use obtained via questionnaire. Renal markers (urea and creatinine) were assessed by blood collection. Buccal mucosa cells were collected to assess MNi frequency by buccal micronucleus cytome assay. Moderation was tested using multiple linear regression models by PROCESS macro for SPSS. Results showed significant interactions for supplement use (p = 0.001) and supplement type, ergogenic (p = 0.003) and sports food (p = 0.003), with MNi for urea. For creatinine, only supplement use showed interaction with MNi frequency (p = 0.048). In conclusion, supplement intake is a moderator in the relationship between MNi frequency and renal function markers in gym members.

Intestinal transit rhythm and associated factors during the COVID-19 pandemic: A pilot study.

BACKGROUND & AIMS: Social distancing may lead to changes in lifestyle, such as the reduction in physical exercise practice, dietary changes, weight alterations, as well as intestinal rhythm. Our study aimed to investigate the intestinal transit rhythm of adults during social distancing due to the COVID-19 pandemic, in association with sociodemographic variables, physical activity, nutritional status, frequency of food intake, and water intake. METHODS: Our cross-sectional study comprised an online questionnaire that was shared by the internet concerning demographic information (sex and age); physical activity; anthropometric data (reported weight and height); dietary habits information (food frequency of simple high-carbohydrates foods, whole food, and processed foods; water intake; intestinal transit rhythm). The survey was conducted from April and July 2020. Statistical analysis was performed using Pearson's chi-square test (χ2) or Fisher's exact test, considering p < 0.05. RESULTS: During social distancing, 72.5% of the respondents presented an adequate intestinal transit rhythm, and 27.5% had inadequate intestinal transit rhythm (19.0% slow and 8.5% rapid intestinal transit rhythm). Intestinal transit rhythm differs between sex, with women presenting significantly higher odds for altered bowel rhythm, compared to men (OR (95% CI) = 2.324 (1.027-5.257); p = 0.043). Also, results showed that individuals who frequently ingest simple high carb foods have high prevalence of slow intestinal transit rhythm (63%, p = 0.032). CONCLUSION: In this study, we found a higher prevalence of adequate intestinal transit during social distancing due to the COVID-19 pandemic. Women had significantly higher odds for altered bowel rhythm, compared to men. Frequent consumption of simple carbohydrates was associated with a higher prevalence of slow intestinal transit rhythm.

Potential Ameliorative Effects of Chromium Supplementation on Glucose Metabolism, Obesity, and Genomic Stability in Prediabetic Rat Model.

Chromium (III) (Cr(III)) effect on improving glucose, body mass loss, and genomic stability has been extensively studied in models of type 2 diabetes. However, there is a lack of studies evaluating its effect on prediabetes. Thus, this study evaluates the effects of Cr(III) as dietetic supplementation on glucose metabolism, obesity, and genomic stability on prediabetic rat model using high-invert sugar. Male Wistar rats were divided randomly into four treatment groups: (1) control, receiving standard diet (control); (2) prediabetic (PD), receiving a 32% of invert sugar; (3) Cr(III), receiving chromium (III) chloride (CrCl3•6H2O) (58.4 mg/L); and (4) Cr(III) + PD, receiving CrCl3•6H2O in combination with high-invert sugar. Cr(III) supplementation significantly reduced blood glucose (123.00 ± 8.29 mg/dL vs. 115.30 ± 9.31 mg/dL, p = 0.015) and partially reduced area under the 120-min blood glucose response curve (AUC) in PD rats (p = 0.227). Moreover, Cr(III) attenuated weight gain (187.29 ± 38.56 g vs. 167.22 ± 29.30 g, p = 0.004), significantly reducing body mass index (0.68 ± 0.04 g/cm2 vs. 0.63 ± 0.04 g/cm2, p < 0.001), Lee index (0.30 ± 0.01 vs. 0.28 ± 0.01, p < 0.001), and peritoneal fat (p < 0.001). Regarding genomic stability, high-invert sugar, Cr(III), or the combination of both did not produce changes in oxidative stress, DNA damage in pancreas, or cytotoxicity markers. These data suggest that Cr(III) supplementation improved partially glucose metabolism and reduced obesity in rat model PD due to high-invert sugar without influence in genomic stability.

Iron Overload Impairs Autophagy: Effects of Rapamycin in Ameliorating Iron-Related Memory Deficits.

Over the years, iron accumulation in specific brain regions has been observed in normal aging and related to the pathogenesis of neurodegenerative disorders. Many neurodegenerative diseases may involve cognitive dysfunction, and we have previously shown that neonatal iron overload induces permanent cognitive deficits in adult rats and exacerbates age-associated memory decline. Autophagy is a catabolic pathway involved in the removal of toxic protein aggregates, which are a hallmark of neurodegenerative events. In the present study, we investigated whether iron accumulation would interfere with autophagy and also sought to determine the effects of rapamycin-induced stimulation of autophagy in attenuating iron-related cognitive deficits. Male Wistar rats received a single daily oral dose of vehicle or iron carbonyl (30 mg/kg) at postnatal days 12-14. In adulthood, they received daily intraperitoneal injections of vehicle or rapamycin (0.25 mg/kg) for 14 days. Results showed that iron given in the neonatal period impaired inhibitory avoidance memory and induced a decrease in proteins critically involved in the autophagy pathway, Beclin-1 and LC3, in the hippocampus. Rapamycin in the adulthood reversed iron-induced memory deficits, decreased the ratio phospho-mTOR/total mTOR, and recovered LC3 II levels in iron-treated rats. Our results suggest that iron accumulation, as observed in neurodegenerative disorders, hinders autophagy, which might play a role in iron-induced neurotoxicity. Rapamycin, by inducing authophagy, was able to ameliorate iron-induced cognitive impairments. These findings support the use of rapamycin as a potential neuroprotective treatment against the cognitive decline associated to neurodegenerative disorders.