Are there any remarkable effects of prenatal exposure to food colourings on neurobehaviour and learning process in rat offspring?

OBJECTIVE: Artificial food colourings and additives (AFCAs) have long been discussed to have adverse effects on cognition and behaviour in children. In this study, our aim was to assess the probable side effects of prenatal exposure to colouring food additives on neurobehaviour and spatial learning process. METHODS: We administered 'no observable adverse effect levels' (NOAELs) of common used AFCAs as a mixture (erythrosine, Ponceau 4R, Allura Red AC, Sunset yellow FCF, tartrazine, Amaranth, Brilliant Blue, Azorubine and Indigotine) to female rats before and during gestation and tested their effects on spatial working memory and behaviour in their offspring. Effects of AFCAs on spatial working memory were evaluated by Morris water maze, behavioural and locomotor effects by open-field and forced-swim tests. RESULTS: Prenatal exposure to commonly used AFCAs had no adverse effects on spatial working memory; however, assessment of interaction of sex and AFCAs on 'latency to locate the visible platform', which was used as a measure of motivation, showed a significant interaction (P < 0.05) on female rats. In addition, AFCAs caused an increase in anxiolytic like effect in the open-field test (P < 0.05) and an increase in mobility time (P < 0.05) in the forced-swim test. We also detected a significant interaction of sex and AFCAs on forced-swim test parameters (P < 0.05). DISCUSSION: These findings indicated that prenatal exposure to NOAELs of AFCAs resulted in implicit adverse effects that caused an increase in motility and a decrease in motivation and anxiety in offspring in sex-related manner.

Juniperus communis Linn oil decreases oxidative stress and increases antioxidant enzymes in the heart of rats administered a diet rich in cholesterol.

It has been asserted that consumption of dietary cholesterol (Chol) raises atherosclerotic cardiovascular diseases and that Chol causes an increase in free radical production. Hypercholesterolemic diet has also been reported to cause changes in the antioxidant system. In our study, different doses of Juniperus communis Linn (JCL) oil, a tree species growing in Mediterranean and Isparta regions and having aromatic characteristics, were administered to rats; and the levels of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and thiobarbituric acid reactive substances assay (TBARS) were examined in the heart tissue of rats. In this study, 35 Wistar Albino male adult rats weighing approximately 250-300 g were used. The rats were divided into five groups of seven each. The control group was administered normal pellet chow, and the Chol group was administered pellet chow including 2% Chol, while 50 JCL, 100 JCL, and 200 JCL groups were administered 50, 100, and 200 mg/kg JCL oil dissolved in 0.5% sodium carboxy methyl cellulose, respectively, in addition to the pellet chow containing 2% Chol, by gavage. After 30 days, the experiment was terminated and the antioxidant enzyme activities were examined in the heart tissue of rats. While consumption of dietary Chol decreases the activities of SOD, GSH-Px, and CAT in heart tissue of rats (not significant), administeration of 200 mg/kg JCL oil in addition to Chol led to a significant increase in the activity of antioxidant enzymes. Administering Chol led to a significant increase in TBARS level. Administering 100 and 200 mg/kg JCL oil together with Chol prevented significantly the increase in lipid peroxides. As a result of the study, JCL oil showed oxidant-antioxidant effect in the heart tissue of rats.

The effect of micronized purified flavonoid fraction on the prevention of testicular pathologies in adolescent rats with experimentally induced varicocele.

PURPOSE: We investigated the effect of micronized purified flavonoid fraction on the prevention of testicular pathologies following varicocele induction. MATERIALS AND METHODS: A total of 66 adolescent (6-week-old) male Wistar rats were included in study. Rats were divided into 7 groups, including group 1--control, group 2--sham operation, group 3--left varicocele induced, group 4--varicocele induced, varicocelectomy done 4 weeks later and micronized purified flavonoid fraction administered for 4 weeks, group 5--varicocele induced and micronized purified flavonoid fraction administered for 8 weeks, group 6--varicocele induced and beginning 4 weeks later micronized purified flavonoid fraction administered for 4 weeks, and group 7--varicocele induced and varicocelectomy done 4 weeks later. Before sacrifice bilateral real-time testicular microvascular perfusion of all rats was measured using the PeriFlux System 5000 PF 5010 LDPM Unit (Perimed, Järfälla, Sweden). All testes were graded according to the Johnsen scoring system. To assess apoptosis caspase-3 levels were measured. RESULTS: Testicular weight in group 3 was markedly decreased and the extent of seminiferous tubular damage was significantly increased compared with the other groups. Bilateral testicular blood flow and the number of apoptotic germ cells were greater in group 3. Significantly higher Johnsen scores and a meaningful decrease in the apoptotic index were detected in groups 4 to 7 compared with group 3. CONCLUSIONS: We observed favorable effects of micronized purified flavonoid fraction on the regression of testicular damage secondary to varicocele.

Salivary glands of fetuses are adversely affected by artificial food colorings in rats.

OBJECTIVE: Artificial food colorings, as types of food additives, are widely used at present in daily life. We aimed to investigate the effects of exposure to artificial food colorings during the intrauterine period on the salivary glands in adulthood. METHODS: A total of 30 Wistar albino female pregnant rats were included in this study. The treatment group was given a mixture of nine artificial food colorings at no observed adverse-effect-level doses. Neither mothers nor offspring were fed with food colorings after delivery. When the offspring became adults, they were sacrificed, and the possible histopathological and immunohistochemical effects of artificial food colorings on the salivary glands were investigated. In these glands, anti-matrix metallopeptidase 2 (anti-MMP2), anti-MMP9, anti-tissue inhibitor of metalloproteinases (TIMP) metallopeptidase inhibitor 1 (anti-TIMP1), anti-TIMP2, and anti-TIMP3 were examined. RESULTS: The expressions of anti-MMP2, anti-TIMP1, anti-TIMP2, and anti-TIMP3 parameters were found to be higher in treatment groups (p<0.05). CONCLUSION: It was suggested that intrauterine exposure of synthetic food colorings may lead to deterioration of the tissue structure of the salivary glands in adulthood, thereby increasing susceptibility to chronic illnesses including malignancy and chronic inflammation. Therefore, pregnant women should give importance to their nutrition in terms of foods containing synthetic colorings.

Association of serum fetuin-A with valvular calcium concentration in rheumatic mitral valve disease.

BACKGROUND AND AIM OF THE STUDY: Fetuin-A is an acute-phase glycoprotein that inhibits ectopic calcification. The study aim was to assess serum fetuin-A levels in patients with rheumatic mitral valve disease (RMVD), and to evaluate the association of fetuin-A with the extent of mitral valve calcification, determined either echocardiographically or by the measurement of calcium and phosphorus concentrations in the resected valve tissues. METHODS: The study group comprised 21 patients (14 females, seven males; mean age 48 +/- 12.4 years) with RMVD, who were scheduled for mitral valve replacement surgery, while 30 age- and gender-matched healthy subjects (17 females, 13 males; mean age 43.6 +/- 11.1 years) served as a control group. Baseline serum fetuin-A levels were measured using ELISA, and high-sensitivity C-reactive protein (hs-CRP) levels using immunonepholometry. A Wilkins score was calculated using transesophageal echocardiography, and the resected valve tissues were analyzed for concentrations of calcium and phosphorus. RESULTS: Serum fetuin-A levels were lower and hs-CRP levels higher in the study group than in controls (300.4 +/- 92.5 microg/ml versus 352.6 +/- 55.3 microg/ml, p = 0.028; and 1.9 +/- 1.2 mg/dl versus 0.3 +/- 0.2 mg/dl, p < 0.0001, respectively). An inverse correlation was found between serum fetuin-A and hs-CRP levels (r = -0.690, p = 0.001). A significant association of either serum fetuin-A or hs-CRP was also found to occur with calcium concentration in the mitral valve tissue (r = -0.684, p = 0.001, and r = 0.510, p = 0.018, respectively), but not with the Wilkins calcium score. Serum fetuin-A and phosphorus concentrations in the MV tissue were independent predictors of calcium concentration in the MV tissue. CONCLUSION: Serum fetuin-A, which is significantly decreased in patients with RMVD, is an independent predictor of calcium concentration in the mitral valve tissue.

The significance of urinary beta-2 microglobulin level for differential diagnosis of familial Mediterranean fever and acute appendicitis.

The clinical and laboratory parameters widely used are not specific to discriminate the abdominal pain due to FMF attack from that of acute appendicitis. The present study aims to investigate the urinary beta-2 microglobulin (U-ß2M) level as a potential parameter to identify these two diseases mimicking each other. A total of 51 patients with established FMF diagnosis due to Tel Hashomer criteria on colchicine treatment (1-1.5 mg/day), 15 patients with acute appendicitis who had appropriate clinical picture and were also supported pathologically after the surgery, and 20 healthy controls were enrolled in the study. Of the 51 patients with FMF, 25 were at an attack period, while remaining 26 were not. For the diagnosis of acute attack, as well as physical examination, laboratory tests including white blood cell count, C-reactive protein, and erythrocyte sedimentation rate were performed. From urine specimens U-ß2M, microalbumin, and N-acetyl glucosaminidase (U-NAG) were measured. U-ß2M levels were significantly higher in acute appendicitis group compared to FMF attack, FMF non-attack, and control groups (p < 0.001, p < 0.001, and p < 0.001, respectively). U-NAG and microalbuminuria were significantly higher in acute appendicitis, FMF attack, and FMF non-attack groups compared to controls (U-NAG p < 0.001, p = 0.016, p = 0.004, microalbuminuria p < 0.001, p < 0.001, p < 0.001, respectively). Microalbuminuria was significantly higher in acute appendicitis group compared to the FMF attack group (p = 0.004). Determination of U-ß2M levels may be helpful for differential diagnosis of peritonitis attacks of FMF patients on colchicine treatment and acute appendicitis. However, this finding should be substantiated with other studies.

Salivary glands of fetuses are adversely affected by artificial food colorings in rats

SUMMARY OBJECTIVE: Artificial food colorings, as types of food additives, are widely used at present in daily life. We aimed to investigate the effects of exposure to artificial food colorings during the intrauterine period on the salivary glands in adulthood. METHODS: A total of 30 Wistar albino female pregnant rats were included in this study. The treatment group was given a mixture of nine artificial food colorings at no observed adverse-effect-level doses. Neither mothers nor offspring were fed with food colorings after delivery. When the offspring became adults, they were sacrificed, and the possible histopathological and immunohistochemical effects of artificial food colorings on the salivary glands were investigated. In these glands, anti-matrix metallopeptidase 2 (anti-MMP2), anti-MMP9, anti-tissue inhibitor of metalloproteinases (TIMP) metallopeptidase inhibitor 1 (anti-TIMP1), anti-TIMP2, and anti-TIMP3 were examined. RESULTS: The expressions of anti-MMP2, anti-TIMP1, anti-TIMP2, and anti-TIMP3 parameters were found to be higher in treatment groups (p<0.05). CONCLUSION: It was suggested that intrauterine exposure of synthetic food colorings may lead to deterioration of the tissue structure of the salivary glands in adulthood, thereby increasing susceptibility to chronic illnesses including malignancy and chronic inflammation. Therefore, pregnant women should give importance to their nutrition in terms of foods containing synthetic colorings.

Effects of maternally exposed food coloring additives on laryngeal histology in rats.

Experimental reports showed carcinogenic effects of artificial food colors and additives (AFCAs) on many organs, including the head and neck region. We aimed to investigate the effect of AFCAs on laryngeal histomorphology and immunohistochemical expression in maternally exposed rats. "No observable adverse effect levels" of commonly used AFCAs as a mixture were given to female rats before and during gestation. Histopathological and immunohistochemical findings were evaluated in their offspring. Significant decreasing in goblet cell count and cilia loss were observed with AFCAs in maternally exposed rats (p<0.05). Immunohistochemically, the Ki67 index was significantly increased and villin expression was significantly reduced in laryngeal epithelium in the study group (p<0.05), whereas expression of cyclooxygenase type 2, Muc-2, Muc-5AC, p53, and epidermal growth factor receptors did not differ between the groups. This study demonstrated that maternal exposure of AFCAs plays a role in the mucosal defense system and possibly in carcinogenesis.

The effects of chelators on zinc levels in patients with thalassemia major.

Zinc which is an essential element has very important effects on growth and immune system in patients with thalassemia major (TM). The effects of two oral iron chelator agents, desferrioxamine (DFO) and deferiprone (DFP), on zinc levels were investigated in previous studies and they were found to cause zinc deficiency. Zinc level alteration by the new chelator deferasirox (DFX) is not present in the literature. The aim of this study was to examine the effects of different oral chelators on serum and urine zinc levels in TM patients. Zinc levels are compared in the patients who received different chelators: only DFX, combined chelation with DFO plus DFP and the healthy control group. A total of 56 patients with TM were involved in this study: 39 patients received only DFX and 17 patients were given combined treatment DFO+DFP between August 2008 and August 2009. In addition, a control group was established from the healthy population. Blood was taken from all the patients for serum zinc levels and 24hour-urine samples were collected for urine zinc levels. Serum zinc levels were found to be 64.8±14.8µg/dL in DFX group and 66.5±15.1µg/dL in DFO+DFP group. These levels were statistically lower than that in the control group (149±54.3µg/dL) (p<0.05), but there was no statistically difference between the two different chelation groups (p>0.05). The urine zinc levels of DFX and DFO+DFP group were 662.2±428.2µg/day and 1182.3±980.3µg/day respectively (p<0.05). Urinary zinc excretion in the chelation groups (DFX and DFO+DFP) was significantly higher than the control group (395.1±208.9µg/day) (p<0.05). As a conclusion, the new chelation agent, DFX, also leads to zinc deficiency, though its urinary zinc excretion is lower. New studies are required to examine the effects of DFX on zinc extensively. Zinc levels of patients with TM should be followed up regularly and zinc supply should be given at early ages.

The effect of electromagnetic radiation on the rat brain: an experimental study.

AIM: The aim of this study is to determine the structural changes of electromagnetic waves in the frontal cortex, brain stem and cerebellum. MATERIAL AND METHODS: 24 Wistar Albino adult male rats were randomly divided into four groups: group I consisted of control rats, and groups II-IV comprised electromagnetically irradiated (EMR) with 900, 1800 and 2450 MHz. The heads of the rats were exposed to 900, 1800 and 2450 MHz microwaves irradiation for 1h per day for 2 months. RESULTS: While the histopathological changes in the frontal cortex and brain stem were normal in the control group, there were severe degenerative changes, shrunken cytoplasm and extensively dark pyknotic nuclei in the EMR groups. Biochemical analysis demonstrated that the Total Antioxidative Capacity level was significantly decreased in the EMR groups and also Total Oxidative Capacity and Oxidative Stress Index levels were significantly increased in the frontal cortex, brain stem and cerebellum. IL-1ß level was significantly increased in the EMR groups in the brain stem. CONCLUSION: EMR causes to structural changes in the frontal cortex, brain stem and cerebellum and impair the oxidative stress and inflammatory cytokine system. This deterioration can cause to disease including loss of these areas function and cancer development.

Serum placental growth factor, vascular endothelial growth factor, soluble vascular endothelial growth factor receptor-1 and -2 levels in periodontal disease, and adverse pregnancy outcomes.

BACKGROUND: The aim of this study is the evaluation of levels of serum interleukin (IL)-1ß, IL-6, IL-10, tumor necrosis factor (TNF)-α, vascular endothelial growth factor (VEGF), placental growth factor (PIGF), and soluble VEGF receptor (sVEGFR)-1 and -2 in the association between periodontal disease and adverse pregnancy outcomes. METHODS: One hundred and nine mothers, who recently gave birth, and 51 women who were not recently pregnant, aged 18 to 35 years, were included in this study. The mothers were classified as term birth, preterm birth (PTB), and preterm low birth weight (PLBW) in respect to their gestational age and baby's birth weight. The birth mothers were grouped as having gingivitis or periodontitis. The non-pregnant group also included periodontally healthy patients. Venous blood samples were collected to evaluate serum IL-1ß, IL-6, IL-10, TNF-α, VEGF, PIGF, and sVEGFR-1 and -2 levels. RESULTS: Mother's weight, education, and income level were significantly associated with pregnancy outcomes. Serum levels of IL-1ß, TNF-α, IL-6, VEGF, and sVEGFR-1 and -2 showed an increase in significance when related to pregnancy. Whereas in the PLBW group IL-1ß, VEGF, and sVEGFR-2 levels were increased, in the PTB group sVEGFR-1 levels were increased. Additionally, the patients in the PLBW group with periodontitis had higher serum levels of IL-1ß, VEGF, sVEGFR-2, and IL-1ß/IL-10. CONCLUSION: The serum levels of IL-1ß, VEGF, and sVEGFR-1 and -2 may have a potential effect on the mechanism of the association between periodontal disease and adverse pregnancy outcomes.

Serum copper, zinc, and magnesium levels in patients with chronic fluorosis.

Although there are many studies on effect of fluoride on trace elements in experimental animals, few studies exist on serum trace elements levels in patients with endemic fluorosis. We aimed to determine the serum levels of trace elements including serum copper (Cu), zinc (Zn), and serum levels of minerals including calcium (Ca), phosphorus (P), magnesium (Mg), sodium (Na), potassium (K) in patients with endemic fluorosis. The study group consisted of 30 patients with endemic fluorosis (17 females, 13 males, mean age 33.53±9.85 years). An age, gender, and body mass index matched 30 healthy volunteers comprised control group (21 females, ten males with a mean age 33.93±7.39 years). Urine fluoride levels of chronic fluorosis patients were significantly higher than that of control subjects as expected (1.92±0.10 mg/l vs. 0.41±0.09 mg/l, respectively; P<0.001). Serum Cu levels (89.14±16.77 µg/dL vs. 102.69±25.04 µg/dL, respectively, P=0.017), serum Zn levels (77.98±20.58 µg/dL vs. 94.57±35.87µg/dL, respectively, P=0.032), and serum Mg levels (1.92±0.18 mg/dL vs. 2.07±0.31 mg/dL, respectively, p=0.022) was significantly lower in chronic fluorosis patients than in controls. There were no statistically significant differences between the fluorosis group and control group with respect to serum levels of Na, K, Ca, and P. We concluded that chronic fluorosis is associated with reduced serum levels of Cu, Zn, and Mg.

The efficacy of single-dose 5-fluorouracil therapy in experimental caustic esophageal burn.

INTRODUCTION: Accidental ingestion of caustic substances may cause serious problems in children. Approximately 20% of caustic ingestions result in esophageal stricture formation, resulting from excessive collagen synthesis to the extracellular matrix by fibroblasts. Recent studies showed that a single application of 5-fluorouracil (5-FU) is a very effective inhibitor of fibroblast proliferation and differentiation for prolonged periods. Using an experimental model, we investigated the efficacy of single-dose 5-FU on stricture formation after caustic esophageal burn. MATERIALS AND METHODS: Forty Wistar-Albino rats were divided randomly into 4 equal groups: group 1 (sham-operated group), the esophagus was uninjured and untreated; group 2 (control group), the esophagus was injured and left untreated; group 3 (intraperitoneal treatment group), the esophagus was injured and treated immediately after the burn injury with a single intraperitoneal dose (20 mg/kg) of 5-FU; group 4 (local treatment group), the esophagus was injured and treated immediately after the burn injury with a single intraesophageal application of 5-FU at a concentration of 25 mg/mL. Caustic esophageal burn was produced by instilling 10% NaOH in the distal esophagus. The distal esophagi were harvested at 28 days postoperatively. Histologic sections were assessed by measuring the stenosis index (SI) and histopathologic damage score. Hydroxyproline (HP) levels in the tissues were determined biochemically. RESULTS: There were significant reductions in the SI (P < .05), histopathologic damage score (P < .05), and HP level (P < .05) in the intraperitoneal treatment group when compared with the control group. No significant differences in the SI and histopathologic damage score were detected between the control and local treatment groups (P > .05), whereas significant reduction in the HP level was determined between these groups (P < .05). CONCLUSION: A single intraperitoneal dose of 5-FU had a preventive effect on stricture formation after caustic esophageal burn. This observation suggests that 5-FU may prevent this undesirable complication in the clinical setting. Clinical studies are now required to verify this form of treatment. Local intraesophageal application of 5-FU immediately after the burn injury was not effective. Further investigations are required to determine the appropriate timing of application of 5-FU at the local site of injury.

Increased neopterin levels and its association with angiographic variables in patients with slow coronary flow: an observational study.

OBJECTIVE: Although various inflammatory markers have been studied in patients with slow coronary flow (SCF), serum neopterin levels have not been studied previously. We investigated the serum neopterin and high sensitivity C-reactive protein (hs-CRP) levels and the relationship between neopterin and hs-CRP levels and TIMI flow in patients with SCF. METHODS: The study group consisted of 51 patients with SCF. An age and gender matched control group was composed of 40 subjects. Coronary flow rates of all patients and control subjects were documented by Thrombolysis in Myocardial Infarction (TIMI) frame count. We measured serum neopterin and hs-CRP levels at the same time in patients with SCF and control subjects in this cross-sectional observational study. Chi-square, Mann-Whitney U and unpaired t tests, Pearson correlation and linear regression analyses were used for statistical analysis. RESULTS: The TIMI frame counts for all coronary arteries and the mean TIMI frame count were significantly higher in the SCF group than controls. Serum neopterin levels were significantly higher among patients with SCF when compared with control group (2.13±1.03 vs. 1.60±0.50 ng/ml; p=0.004). Serum hs-CRP levels were significantly higher among patients with SCF when compared with control group (2.06±1.32 vs. 0.74±0.40 mg/L respectively; p<0.001). There was a significant association of serum neopterin levels (ß=0.60, 95% CI: 4.93-9.06, p<0.001) and serum hs-CRP levels (ß=0.29, 95%CI: 0.84-4.33, p=0.004) with mean TIMI frame count independent of potential confounders such as age, gender, body mass index, smoking, glucose and cholesterol levels. CONCLUSION: We have shown that serum neopterin and hs-CRP levels were significantly elevated in patients with SCF when compared with control subjects. Serum neopterin and hs-CRP levels were correlated with mean TIMI frame count in patients with SCF.