Body Weight Gain In Males Research Articles

Maternal probiotic supplementation protects against PBDE-induced developmental, behavior and metabolic reprogramming in a sexually dimorphic manner: Role of gut microbiome

AbstractPolybrominated diphenyl ethers (PBDEs) are endocrine-disrupting persistent organic pollutants (POPs) used as flame retardants in a wide range of commercial applications. We have previously reported neurobehavioral and metabolic reprogramming produced by developmental PBDEs. PBDEs perturb the microbiome, an influencer of life-long health, while probiotic supplementation with Limosilactobacillus reuteri (LR) can avert neurobehavioral and endocrine disruption. We, therefore, tested the hypothesis that perinatal maternal LR supplementation would protect gut microbiome richness and diversity, developmental milestones, adult neurobehavior and metabolic homeostasis in PBDE-exposed offspring. C57BL/6N dams were orally exposed to a commercial penta-mixture of PBDEs, DE-71, at 0.1 mg/kg/day, or corn oil vehicle (VEH/CON) during gestation and lactation. Mice offspring received DE-71 or VEH/CON with or without co-administration of LR (ATCC-PTA-6475) indirectly via their mother from gestational day (GD) 0 until postnatal day (P)21 (Cohort 1), or continued to receive LR directly from P22 through adulthood (Cohort 2). Results of fecal 16S rRNA sequencing indicated age- and sex-dependent effects of DE-71 on gut microbial communities. Maternal LR treatment protected against DE-71-induced reduction in α-diversity in P22 females and against β-diversity alterations in P30 males. In females, DE-71 changed the relative abundance of specific bacterial taxa, such as Tenericutes and Cyanobacteria (elevated) and Deferribacterota (reduced). In males, several Firmicutes taxa were elevated, while Proteobacteria, Chlamydiae, and several Bacteroidota taxa were reduced. The number of disrupted taxa normalized by maternal LR supplementation was as follows: 100% in P22 females and 33% in males at P22 and 25% at P30. Maternal LR treatment protected against DE-71-induced delay of postnatal body weight gain in males and ameliorated the abnormal timing of incisor eruption in both sexes. Further, DE-71 produced exaggerated digging in both sexes as well as locomotor hyperactivity in females, effects that were mitigated by maternal LR only in females. Other benefits of LR therapy included normalization of glucose tolerance, insulin-to-glucose ratio and plasma leptin in adult DE-71 females (Cohort 2). This study provides evidence that probiotic supplementation can mitigate POP-induced reprogramming of neurodevelopment, adult neurobehavior, and glucose metabolism in association with modified gut microbial community structure in a sex-dependent manner.

Chronic sleep restriction during juvenility alters hedonic and anxiety-like behaviours in a sex-dependent fashion in adolescent Wistar rats.

Chronic reduction of sleep time in children and adolescents has been related to increased incidence of anxiety and depression. In rats, protocols of protracted sleep deprivation or chronic sleep restriction (CSR) are considered a stressor. In previous studies we showed that post-weaning CSR in male rats induces anxiety-like behaviour and changes in neurotransmission in emotion-related brain areas. In the present study we examined whether the effects of this adversity are sex-dependent. Twenty-two litters, containing four males and four females were distributed into control (CTL) and CSR groups. CSR began on postnatal day (PND) 21 and lasted for 21 days; each day the animals were placed onto small platforms immersed in water for 18 h and were allowed to sleep freely in their home-cages for the remaining 6 h. Throughout the CSR, all animals underwent the sucrose splash test once/week to assess their self-care and hedonic behaviours. Body weight was measured on PNDs 21 and 42. At the end of CSR period, the adolescents were allowed to sleep freely for 2 days, after which, behavioural tests began. Within each litter, one male and one female (pair) were not tested and provided blood and brain for determination of basal corticosterone (CORT) levels and hippocampal BDNF. One pair was tested in the sucrose preference test (SPT), one pair on the elevated plus maze (EPM) and one pair in the forced swim test (FST). CORT was measured after all conditions. CSR impaired self-care behaviour and body weight gain in males and females and increased relative adrenal weight only in males. There were no changes in sucrose intake in the SPT; CSR females displayed less immobility in the FST and CSR males displayed more anxiety-like behaviour in the EPM. CORT levels were similar between CTL and CSR males, whilst lower in CSR females than CTL ones in all experimental conditions. No changes in BDNF levels were detected in the dorsal hippocampus of CSR rats. The results indicate that CSR impaired self-care behaviour in both sexes, but only males displayed anxiety-like behaviour, whilst sleep recovery in females appeared to normalise their behaviour.

Intermittent Fasting Resolves Dyslipidemia and Atherogenesis in Apolipoprotein E-Deficient Mice in a Diet-Dependent Manner, Irrespective of Sex.

In humans and animal models, intermittent fasting (IF) interventions promote body weight loss, improve metabolic health, and are thought to lower cardiovascular disease risk. However, there is a paucity of reports on the relevance of such nutritional interventions in the context of dyslipidemia and atherosclerotic cardiovascular diseases. The present study assessed the metabolic and atheroprotective effects of intermittent fasting intervention (IF) in atherosclerosis-prone apolipoprotein E-deficient (Apoe-/-) mice. Groups of male and female Apoe-/- mice were fed a regular (chow) or atherogenic (high-fat, high-cholesterol, HFCD) diet for 4 months, either ad libitum or in an alternate-day fasting manner. The results show that IF intervention improved glucose and lipid metabolism independently of sex. However, IF only decreased body weight gain in males fed chow diet and differentially modulated adipose tissue parameters and liver steatosis in a diet composition-dependent manner. Finally, IF prevented spontaneous aortic atherosclerotic lesion formation in mice fed chow diet, irrespective of sex, but failed to reduce HFCD-diet-induced atherosclerosis. Overall, the current work indicates that IF interventions can efficiently improve glucose homeostasis and treat atherogenic dyslipidemia, but a degree of caution is warranted with regard to the individual sex and the composition of the dietary regimen.

ESTIMASI KOMPONEN RAGAM DAN HERITABILITAS BOBOT BADAN PERIODE STARTER AYAM LOKAL

This study aims to determine the diversity and heritability components of the nature of body weight production of local chickens aged 0-4 weeks. The material used in this study were 95 local chickens from 4 male and 20 female. Heritability calculation (h2) uses the nested design method. The results showed the value of heritability (h2) DOC weights in male body weights were 0.429851 and 0.569476 in the third week, while the largest variance component in the third week was 12.28387 and for female in the fourth week was 59.333934 . Heritability (h2) DOC weights for male body weight gain were 0.6840 and 0.5257 in the third week, the variance component given from the largest male was in the fourth week ie 0.39037 and for female in the second week was 0.68931.

Impact of graded maternal dietary fat content on offspring susceptibility to high-fat diet in mice.

Maternal high-fat diet (HFD) increases offspring obesity, yet the impacts of different levels of maternal dietary fat have seldom been addressed. In mice, the impact of graded maternal dietary fat on offspring adiposity and offspring's later susceptibility to HFD were assessed. Lactating mice were fed diets with graded fat content from 8.3% to 66.6%. One male and one female pup from each litter were weaned onto a low-fat diet for 15 weeks. HFD (41.7%) was then introduced to half of the offspring for 12 weeks. Offspring body weight and adiposity were positively related to maternal dietary fat content and were higher when mothers were exposed to HFD. The maternal diet effect was nonlinear and sex dependent. A maternal dietary fat of 41.7% and above exaggerated the offspring body weight gain in males but was not significant in females. Maternal 8.3% fat and 25% fat diets led to the highest daily energy expenditure and respiratory exchange ratio in offspring. Offspring fed a low-fat diet had higher daily energy expenditure and respiratory exchange ratio than those fed an HFD. Increasing maternal dietary fat during lactation, and HFD in later life, had significant and interacting impacts on offspring obesity. Maternal diet had a bigger impact on male offspring. The effects of maternal dietary fat content were nonlinear.

Effects of regular administration of red wine on testicular profile and body weight in adult male experimental mode

Background: The present study determined whether or not the regular intake of red wine causes any significant changes in testicular and body weight parameters, given the simmering controversy over the effect of alcoholic beverages on health system. Methods: Ten male albino Wistar rats –experimental model with average body weight of 140 g were divided into two groups, A and B, (n=5 each). Group A received distilled water being the control while group B was administered a single daily dose of 5 ml/kg body weight of red wine (Carlo Rossi) for 21 days. An electronic weighing scale (G&G® Neuss, Germany) was used to take record of the initial and final body weights. The animals were anesthetized with isoflurane on the 22nd day to enable collection of the testes which were also weighed and thereafter fixed in 10% neutral formalin for routine histological studies. The analysis of variance (ANOVA) was used with the ‘R’ software to analyze the statistical data, while P<0.05 was taken as the significant value. Results: The micro-anatomical investigation revealed enhanced perfusion of the tissue and normal morphology of the seminiferous tubules with constituent spermatogenic cells at different stages of maturation. The biometric assessment of the organ (testis) weight showed no significant difference; whereas there was a statistically significant increase in the final body weight of the treated-experimental model when compared with the control. Conclusion: The findings indicate that the intake of red wine at the investigated amount may maintain the integrity of the primary reproductive structure and lead to body weight gain in males.

Identification of determining factors size and shape Simbal cattle and Brahman Cross cattle in Pamenang Barat Merangin district

This study aims to determine the determinants of size and shape of Simbal and Brahman Cross cattle in the West Pamenang sub-district, Merangin district. The method of this study was a survey with a purposive sampling technique. Sampling criteria included: Sample of each breeds consisted of 60 Simbal and 60 Brahman Cross cattle aged 1-2 years. Data observed included: body length, shoulder height, chest circumference, inside chest, chest width, canon circumference, hip height, body weight, and body weight gain. The differences in body measurements between Simbal and Brahman Cross cattle analyzed by T-test. Identification of the determinants of size and shape of Simbal and Brahman Cross cattle were analyzed using Main Component Analysis method. The results of this study were body weight, body weight gain, and body measurements of Simbal cattle were significantly different (P &lt;0.05) higher than Brahman Cross cattle, both male and female. Simbal cattle and male Brahman Cross cattle were significantly different (P &lt;0.05) higher than females. The conclusion shows that body weight, body weight gain, and body measurements of Simbal cattle are higher than Brahman Cross cattle. Male body weight gain was higher than females in both Simbal and Brahman Cross cattle. The determining factor for the body size of Simbal and Brahman Cross cattle is chest circumference, while the determining factor for body shape of Simbal cattle is the height of shoulders, while Brahman Cross is body length. The highest correlation between body measurements and body weight in Simbal and Brahman Cross cattle, both male and femal is chest circumference (LD).

Impacts on Hepatic Ontogenic Expression of Drug‐metabolizing Enzymes by High‐fat Diet‐induced Obesity in Mice

The prevalence of obesity‐associated conditions increases up to 30% of general populations globally. A few studies have shown that obesity may lead to altered drug metabolism. Although changed expression of drug‐metabolizing enzymes (DMEs) is reported, the impacts on DMEs due to different obese levels (overweight, obese, and morbidly obese) have not been elucidated. Especially, limited information is available on how obesity alters the expression of DMEs in younger ages. The aim of this study is to investigate impacts of high‐fat diet‐induced obesity (DIO) on the hepatic expression of DMEs in adult and the ontogenic expression in offspring with a focus on cytochrome P450s (CYPs) in a mouse model. The expression of CYPs, as well as constitutive androstane receptor (CAR), pregnane X‐receptor (PXR), hepatocyte nuclear factor (HNF4α), and peroxisome proliferator‐activated receptor α (PPARα) was examined. Adult mice consumed 60 kcal% fat diet (HFD) for 8 or 18 weeks showed a more rapid increase of body weight than 10 kcal% fat diet (LFD) control group. The body weight gain of males was &gt;1.5 fold greater than females in HFD groups. Consistent with the weight gain, fat accumulation was found in the livers of HFD groups. Elevated expression of most selected DMEs and transcription factors was observed in HFD groups, expect for CYP3A16 in 8‐week HFD groups, and CYP1A2 and HNF4α in 18‐week HFD groups. Day 60 offspring derived from HFD‐fed adults showed heavier body weights compared with offspring from LFD‐fed adults. Altered ontogenic expression of CYP1A1, 1A2, 2E1, and UGT1A1 was also observed in HFD offspring. Notably, the changed ontogenic patterns were accompanied by the increased expression of DMEs after day 20 in HFD offspring related to LFD groups. Moreover, similar effects on CAR, PXR, HNF4α, and PPARα were found in HFD offspring, indicating that altered expression pattern of DMEs may due to changed expression of transcription factors. Taken together, our study suggested that obese level of DIO influenced the expression of DMEs in adults and offspring and transcription factors might play roles in the altered expression of DMEs.Support or Funding InformationThis work was supported by grant of NIH R01GM118367 and China Scholarship Council (201707040007).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Cis-1,1,1,4,4,4-hexafluoro-2-butene (HFO-1336mzz-Z) (2018).

Cis-1,1,1,4,4,4-hexafluoro-2-butene (HFO-1336mzz-Z) is a clear, colorless liquid that finds uses as a foam-blowing agent, refrigerant, fire extinguishing agent, and solvent. HFO-1336mzz-Z is not an acute dermal or eye irritant and has very low acute toxicity via inhalation exposure (4-h lethal concentration (LC50) > 102,000 ppm). The no-observed adverse effect level (NOAEL) and lowest-observed adverse effect level (LOAEL) for cardiac sensitization (in epinephrine-challenged dogs) were 12,500 ppm and 25,000 ppm, respectively. In a GLP, subacute (4-week) repeat-dose inhalation study in Crl: CD(SD) male and female rats at exposure concentrations of 0, 2500, 5000, or 10,000 ppm, the only significant observations attributed to exposure were reduced body weight, reduced body weight gain, and reduced food consumption. The study NOAEL was determined to be 2500 ppm. Two separate GLP, 13-week repeat-dose inhalation studies (Organisation for Economic Cooperation and Development (OECD) 413) have been conducted on HFO-1336mzz-Z using male and female Crl: CD (SD) rats. In the first study, exposure concentrations were 0, 500, 1500, or 10,000 ppm, and in the second study, 0, 3000, 4000, 5000, or 7500 ppm. The only significant exposure-related observations in the first study were reductions in body weights, food consumption, and food efficiency in males and females at 10,000 ppm (study NOAEL = 1500 ppm). In the second study, done in part to better define the NOAEL, reductions in body weight and food consumption were observed in males at 7500 ppm; there were no exposure-related observations on these end points in females. Therefore, the study NOAEL was established at 5000 ppm for males and 7500 ppm for females. HFO-1336mzz-Z has also been examined for its potential to produce developmental toxicity in both Crl: CD(SD) rats (0, 500, 1500, or 10,000 ppm) and New Zealand White rabbits (0, 2500, 5000, 7500, or 15,000 ppm) according to GLP and OECD 414. The NOAEL for both maternal and fetal effects in rats was 1500 ppm and the NOAELs for maternal effects and fetal effects in rabbits were 5000 ppm and 7500 ppm, respectively. A non-GLP, two-generation reproductive pilot study, for a planned multigenerational study noted reduced body weight and body weight gain in males at 1500 ppm and above; the NOAEL for this pilot study was set at 500 ppm. There are no chronic toxicity/carcinogenicity studies available, and HFO-1336mzz-Z was not genotoxic/mutagenic in in vitro and in vivo studies. The NOAEL for male rats of 5000 ppm (based on reductions in body weight and food consumption) from the 13-week inhalation study was selected as the point of departure for the derivation of the 8-h time-weighted average (TWA), health-based workplace environmental exposure level (WEEL) value. This subchronic inhalation NOAEL was adjusted to account for duration of exposure, inter-individual variability, and intra-individual variability. The resulting 8-h TWA WEEL value of 500 ppm is fully expected to provide a significant margin of safety against the production of any potential adverse health effects in workers following long-term inhalation exposure to HFO-1336mzz-Z vapor.

Liraglutide pharmacotherapy reduces body weight and improves glycaemic control in juvenile obese/hyperglycaemic male and female rats.

To examine whether the glucagon-like peptide-1 receptor agonist liraglutide could be used in juvenile male and female rats as an anti-obesity/diabetic pharmaceutical to prevent not only adolescent obesity/hyperglycaemia, but also early-adult onset obesity. Pregnant dams were fed either standard chow or a high-fat, high-sucrose diet (HFSD) from gestational day 2, throughout pregnancy and lactation. Offspring were weaned onto the respective maternal diet. Juveniles received daily subcutaneous injection of liraglutide (50 μg/kg, from postnatal day [PND]30 to PND40 and 200 μg/kg from PND40 to PND60) or vehicle. Food intake, body weight and glycaemic levels were evaluated across the experimental period. Chronic liraglutide administration in juveniles prevented body weight gain in males and retained a normoglycaemic profile in both male and female rats. These preclinical data suggest that maternal and early-life consumption of an HFSD increases caloric intake, body weight gain and hyperglycaemia, a collective set of unwanted metabolic effects that appear to be treatable in juveniles with liraglutide pharmacotherapy intervention.

Karakteristik Fenotip dan Genotip Gen GH (Growth Hormon) pada Ayam Tolaki

This study aims to improve the genetic quality of local chickens through genetic approaches and phenotypic characterization for selection purposes. The cGH gene (Chicken Growth Hormone) is one of the genes responsible for local chicken growth traits. Tolaki chicken is a local chicken from Southeast Sulawesi. This study uses the phenotyping method of production and genotyping traits with PCR technique. A total of 50 parents of tolaki chicken were kept 4 weeks. The results showed average body weight of tolaki chicken ranged from 1,395 kg - 1,910 kg, average body weight gain was 58,78 (g / head / week), feed consumption was 81,37 (g / head / day) and ration conversion 9,68. Body weight gain in males was slightly higher (60.30 g / head / mg) compared to females (58.42 g / head / mg). In this study, the presence of the tolaki chicken cGH gene was identified through DNA extraction and amplification through a PCR machine with a length of DNA section of 399 bp.

Establishing maximum tolerated doses for a 2-year combined chronic/carcinogenicity rat study based on toxicokinetic and toxicity gender differences

For agrochemicals tested in a carcinogenicity rodent study, it is often not possible to use the same high dose to achieve maximum tolerated dose (MTDs) without overdosing or insufficiently challenging one gender if significant gender differences are known. Toxicokinetic (TK) data for pesticide FR from a 28-day rat study showed that males required a 3-fold higher external dose compared to females to produce similar internal exposure levels of the parent compound. In the 90-day study, 8%/17% (M/F) decrease in bodyweight gain (BWG) and 15%/15% (M/F) increase in relative liver weights were observed in the 6000 ppm males and 2000 ppm females, respectively. Based on the above TK and toxicity data, different high dose levels were selected for females (1600 ppm) and males (4800 ppm) for a 2-year combined chronic/carcinogenicity study in rats. In the 2-year study, 14%, 13%, 13% and 21% reduction in BWG of males and 10%, 12%, 19% and 20% reduction in BWG of females were observed at weeks 13, 26, 52 and 104, respectively in the highest dose tested. Similar reductions in bodyweight gain in males and females at the different high dose levels clearly demonstrated that appropriate MTDs were reached. Therefore, it is scientifically sound and practical to use TK and toxicity data to use different high dose levels to achieve MTDs for a pesticide with large gender differences.

Sex differences in cardiovascular, neuroendocrine and behavioral changes evoked by chronic stressors in rats

This study investigated the physiological, somatic and behavioral changes evoked by daily exposure to the same type of stressor (homotypic) or different aversive stressor stimuli (heterotypic) in male and female rats. For this, adult Wistar rats were subjected to a 10days regimen of repeated restraint stress (RRS, homotypic stressor) or chronic variable stress (CVS, heterotypic stressor). Effects evoked by CVS included: (i) adrenal hypertrophy and decreased body weight gain in male animals, (ii) a sympathetically-mediated increase in basal heart rate in males, and (iii) a rise in plasma corticosterone concentration and anxiogenic effects in female animals. The homotypic stressor RRS also induced an increase in plasma corticosterone and anxiogenic effects in females, decreased body weight gain in males and evoked a sympathetically-mediated increase in heart rate in both sexes. Changes in cardiovascular function and autonomic activity evoked by both stressors were followed by impairment of baroreflex activity in males, but not female animals. Both chronic stressors evoked changes in blood pressure responsiveness to vasoconstrictor and vasodilator agents in both sexes. Taken together, these results indicate that regardless of chronic stress regimen males are more vulnerable to somatic effects of chronic stressors, while females appear to be more susceptible to neuroendocrine and behavioral changes. Present findings also indicate that females are selectively vulnerable to cardiovascular and autonomic changes evoked by homotypic stressors. Nevertheless, homotypic and heterotypic stressors similarly affect cardiovascular function and autonomic activity in males.

A 28-day oral toxicity study of echimidine and lasiocarpine in Wistar rats

Pyrrolizidine alkaloids (PAs) are a class of naturally-occurring plant toxins. Echimidine is one of the predominant PAs found in honeys produced in Australia and New Zealand. There is a lack of information on the oral toxicity of echimidine on which to base regulatory decisions concerning the risk to humans of these honeys. This GLP study was conducted to assess the subchronic dietary toxicity of echimidine to rats compared to that of lasiocarpine as a positive control. Wistar rats, 10/sex, were fed diets containing 0, 0.6, 1.2 or 2.5 mg/kg bw echimidine. Positive control groups, 10/sex, were fed diets containing 0.6, 1.2 or 2.5 mg/kg bw lasiocarpine.Neither PA had any effect on survival, food consumption, clinical signs, gross lesions, or histopathology. Consumption of lasiocarpine, but not echimidine, decreased bodyweight gain in males at ≥ 1.2 mg/kg bw, and in females at 2.5 mg/kg bw. Slight alterations in white cell counts and serum ALT concentrations at 2.5 mg/kg bw of both PAs were not clinically significant, had no histological correlates, and were considered to be of equivocal relevance.In conclusion, the subchronic No Observed Adverse Effect Level (NOAEL) for echimidine is 2.5 mg/kg bw/day, whereas, on the basis of a treatment-related decrease in bodyweight gain in males at 1.2 mg/kg bodyweight, the NOAEL for lasiocarpine is 0.6 mg/kg bw/day.

Differential expression of feeding-related hypothalamic neuropeptides in the first generation of quails divergently selected for low or high feed efficiency

Livestock and poultry sectors are facing a combination of challenges, including a substantial increase in global demand for high quality animal protein, general droughts and steady rise in animal feed cost. Thus feed efficiency (FE), which defines the animal's ability to convert feed into body weight, is a vital economic and agricultural trait. Genetic selection for FE has been largely used in chickens and has been applied without knowledge of the underlying molecular mechanisms. Although it has made tremendous progress (breast yield, growth rate, egg production), there have been a number of undesirable changes such as metabolic disorders.In the present study we divergently selected male and female quail for high and low FE and we aimed to characterize the molecular basis of these differences at the central level, with the long-term goal of maximizing FE and avoiding the unfavorable consequences.The FE phenotype in first generation quails seemed to be achieved by reduced feed intake in female and increased body weight gain in males. At the molecular level, we found that the expression of feeding-related hypothalamic genes is gender- and line-dependent. Indeed, the expression of NPY, POMC, CART, CRH, melanocortin system (MC1R, MC2R, MC4R, MC5R), ORX, mTOR and ACCα was significantly decreased, however ORXR1/2, AMPKα1, S6K1 and STAT1, 5 and 6 were increased in high compared to low FE males (P<0.05). These genes did not differ between the two female lines. ADPN gene expression was higher and its receptor Adip-R1 was lower in LFE compared to HFE females (P<0.05). In male however, although there was no difference in ADPN gene expression between the genotypes, Adip-R1 and Adip-R2 mRNA abundances were higher in the LFE compared to HFE line (P<0.05).This study identified several key central feeding-related genes that are differentially expressed between low and high FE male and female quails which might explain the differences in feed intake/body weight gain observed between the two lines. Of particular interest, we provided novel insights into central AMPK–mTOR–ACC transcriptional differences between low and high FE quail which may open new research avenues on their roles in the regulation of energy balance and FE in poultry and livestock species.

Safety assessment and single-dose toxicokinetics of the flavouring agent myricitrin in Sprague–Dawley rats

Myricitrin, a flavonol rhamnoside of myricetin extracted from the Chinese bayberry (Myrica rubra Siebold) plant, has been used in Japan since 1992 as a flavour modifier in snack foods, dairy products, and beverages. It is affirmed as generally recognised as safe (GRAS) by the US Flavour and Extract Manufacturer Association (FEMA) and is considered safe by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) at current estimated dietary exposures. In anticipation of expanded marketing, 97% pure myricitrin was fed to male and female Sprague–Dawley rats at dietary concentrations of 0.5%, 1.5% and 5.0% in a 90-day toxicity study. There was increased food consumption and decreased body weight gain in males exposed to 5% myricitrin. Blood values were within laboratory reference ranges except for mean increases in basophils in low- and high-dose males and serum phosphorus in high-dose males. In the absence of abnormal clinical or histopathological changes, these changes are not considered adverse. Based on the 90-day rat toxicity study, the no observed adverse effect level (NOAEL) is 2926 mg kg–1 day–1 in males and 3197 mg kg–1 day–1 in females. Gavage administration of myricitrin resulted in blood levels of myricitrin within 1 h after single oral doses of 250, 500 or 1000 mg kg–1 body weight, indicating direct absorption of the glycosylated form of this flavonoid. Blood levels of myricetin, a metabolite of myricitrin, were not present in rats dosed orally with 1.6 mg kg–1 myricetin, but were present only at 12 or 24 h in one of five, in three of five, and in four of five rats dosed with 250, 500 and 1000 mg myricitrin kg–1 body weight, respectively, possibly a result of hepatic conversion of myricitrin to myricetin and enterohepatic recirculation of the resulting myricetin. The current studies further support prior safety assessments of myricitrin as a food flavouring.

Subchronic Oral Toxicity of Sodium Tungstate in Sprague-Dawley Rats

The subchronic toxicity of sodium tungstate dihydrate aqueous solution in male and female Sprague-Dawley rats was evaluated by daily oral gavage of 0, 10, 75, 125, or 200 mg/kg/d for 90 days. Measured parameters included food consumption, body weight measurements, hematology, clinical chemistry, and histopathological changes. There was a significant decrease in food consumption and body weight gain in males at 200 mg/kg/d from days 77 to 90; however, there was no effect in food consumption and body weights in females. There were no changes in the hematological and clinical parameters studied. Histopathological changes were seen in kidney of male and female and epididymis of male rats. Histopathological changes were observed in the kidneys of male and female rats dosed at 125 or 200 mg/k/d consisting of mild to severe cortical tubule basophilia in 2 high-dose groups. Histological changes in epididymides included intraluminal hypospermia with cell debris in the 200 mg/kg/d dosed male rats. Histopathological changes were observed in the glandular stomach including inflammation and metaplasia in the high-dose groups (125 or 200 mg/kg/d) of both sexes of rats. Based on histopathology effects seen in the kidneys, the lowest observable adverse effect level was 125 mg/kg/d and the no observable adverse effect level was 75 mg/kg/d in both sexes of rats for oral subchronic toxicity.

Rat pancreatitis produced by 13‐week administration of zinc oxide nanoparticles: biopersistence of nanoparticles and possible solutions

Zinc oxide (ZnO) nanoparticles (NPs) are used in diverse applications ranging from paints and cosmetics to biomedicine and food. Although micron-sized ZnO is a traditional food supplement, ZnO NPs are an unknown public health risk because of their unique physicochemical properties. Herein, we studied the 13-week subchronic toxicity of ZnO NPs administered via the oral route according to Organization for Economic Cooperation and Development (OECD) test guideline 408. Well-dispersed ZnO NPs were administered to Sprague-Dawley (SD) rats (11/sex/group) at doses of 67.1, 134.2, 268.4 or 536.8 mg kg(-1) per body weight over a 13-week period. The mean body weight gain in males given 536.8 mg kg(-1) ZnO NPs was significantly lower than that of control male rats, whereas no significant differences were observed between the other treatment groups and the controls. Male and female rats dosed at 536.8 mg kg(-1) ZnO NPs had significant changes in anemia-related hematologic parameters. Mild to moderate pancreatitis also developed in both sexes dosed at 536.8 mg kg(-1) , whereas no histological changes were observed in the other treatment groups. To evaluate the mechanism of toxicity, we performed a bio-persistence study and evaluated the effects of the ZnO NPs on cell proliferation. The treatment of a human gastric adenocarcinoma cell line with ZnO NPs resulted in a significant inhibition of cellular proliferation. The anti-proliferative effect of ZnO NPs or Zn(2+) was effectively blocked by treatment with chelators. These results indicate that the bio-persistence of ZnO NPs after ingestion is key to their toxicity; the no-observed-adverse effect level (NOAEL) of ZnO NPs was found to be 268.4 mg kg(-1) per day for both sexes.

Acute and sub-chronic toxicological assessment of Nannochloropsis oculata in rats

The aim of this study was to investigate the acute and sub-chronic toxicities of Nannochloropsis oculata biomass. In the acute toxicity study, twelve Sprague-Dawley rats of both sexes were gavaged with 12 g/kg body weight (bw) of N. oculata one time, and then tested for morbidity and mortality in 14 days. The oral LD50 of N. oculata in rats was greater than 12 g/kg bw, and no toxicity effects were observed on biomass in terms of morbidity signs, plasma biochemical parameters, organ tissue, or body weight gain in response to N. oculata doses up to 12 g/kg rat bw. In the sub-chronic toxicity study, thirty-six Sprague-Dawley rats of both sexes were chosen and divided into three groups and provided with a diet containing 0, 3, and 6 g of N. oculata per kg bw, respectively, early every morning and then allowed free access to normal food and water ad libitum for 60 days. No biologically significant effects of N. Oculata on organ weights, male body weight gain, or on the plasma biochemical parameters were observed in either treatment group. However, low creatinine and significant differences in body weight gain by female rats were noted in the treatment groups. These changes were not considered as toxicologically significant. The no observable adverse effect level (NOAEL) for N. Oculata under the conditions of this study was 12 g/kg bw/day for acute toxicity and 6 g/kg bw/day for sub-chronic toxicity for both male and female rats. Key words: Toxicity, Nannochloropsis oculata, acute, sub-chronic, rats.

Subacute toxicity assessment of annatto in rat

Increased human use of annatto ( Bixa orellana L), a red yellow food colorant, demands generation of toxicity data. The toxic effects of annatto powder (bixin 27%) have been assessed following administration of a subacute regimen (4 weeks, 20 doses) in Wistar male and female rats. A full study with three dose levels was considered unnecessary since no sign of toxicity had been noted in a preliminary experiment with 1000 mg/kg body weight/day as was recommended by the OECD guideline. In this study, annatto administered by gavage at a dose level of 2000 mg/kg/day decreased male body weight gain, but had no effect on either food intake or food conversion efficiency. Haematological and plasma biochemical examination as well necropsy performed at the end of administration (29th day) and observation (43rd day) periods revealed no alterations related with annatto administration. Kidney apoptosis occurred in 20% treated female rats in restricted areas without proliferation or tubular segments modification. The precise nature of apoptosis was not investigated in the present study. These findings suggest that annatto was no toxic to the rat.