Increase In Weight Of Organs Research Articles

Abstract Tu039: Intestinal atrophy contributes to low-grade inflammation, cardiac dysfunction and metabolic syndrome-like phenotype in a model of heart failure with preserved ejection fraction.

Introduction: Heart failure with preserved ejection fraction (HFpEF) comprises half of all HF cases and lacks effective treatment. HFpEF is now seen as a systemic syndrome often linked to comorbidities like hypertension, obesity, and diabetes. These conditions are commonly associated with unhealthy diets rich in fats but lacking in fiber. We explored the effects of a 3-week exposure to excess mineralocorticoids, salt, and high fat diet (HFD) deficient in fiber. We hypothesize that these challenges lead to intestinal atrophy, contributing to low-grade inflammation that promotes the progression of heart failure and metabolic disease. Methods: We used a mix of 1% saline in drinking water and subcutaneous implantation of controlled-release DOCA pellets (0.83 mg/day) alongside a high-fat diet (60% fat) in 8-week-old female and male C57BL6/J mice. Control mice received a standard chow diet and regular water. Results: The challenge resulted in significant reductions in colon mass, colon length, crypt length, and mucus layer thickness compared to the control group. Additionally, elevated levels of C-reactive protein and IL-6 were detected in the plasma. These changes were accompanied by alterations in diastolic function, including decreased peak myocardial relaxation velocity (e'), elevated E/e' ratio, increased E/A ratio, and prolonged isovolumetric relaxation time (IVRT), while the ejection fraction (EF) remained unchanged. Contractility parameters, such as peak myocardial contraction velocity (s'), declined in challenged mice, along with diminished stroke volume (SV). We also found increased organ weight in the liver, spleen, and lungs indicative of organ congestion. Furthermore, signs of metabolic syndrome were identified, including increased body weight, increased adiposity characterized by gonadal and subcutaneous fat accumulation, and dysglycemia (see Data Table). Conclusions: Our data suggests that in this model, heart failure triggers intestinal hypoperfusion, resulting in intestinal atrophy and compromising the integrity of the intestinal lining. Additionally, a diet rich in fat and lacking in fiber alters the gut environment by diminishing mucus production and promoting a closer interaction between the microbiome and host cells. This compromised mucus layer and intestinal barrier facilitates bacterial wall products to move into the circulation, resulting in a pro-inflammatory state that subsequently affects both cardiac function and metabolism.

Impact of dietary Moringa oleifera leaf supplementation on gut morphometry, behaviour and physiological parameters in growing male rabbits

AbstractMoringa oleifera (MO), a cultivated species of the Moringa, is known for its high concentration of essential nutrients that promote growth. To assess its impact on rabbits' gut morphometric, behavioural, and physiological parameters, a study was conducted using sixty growing male white New Zealand rabbits at 40 days old. The rabbits were divided into four groups and supplemented with dried MO leaves at varying levels (0%, 0.5%, 1% and 2% of body weight) for four weeks. The results revealed significant increases in organ weights, such as liver and intestinal length, and the height of intestinal villi and crypt depth in the large intestine. The muscular layer's and submucosa's thickness also increased in different parts of the intestine in rabbits fed with MO compared to the control group. No significant effect was observed on the caecum mucosa depth. Interestingly, no significant differences were found in body weight or weight gain between the Moringa supplementation groups and the control group. However, rabbits offered 0%, 0.5% and 1% MO spent more time feeding and resting than those given 2% MO. The grooming and sniffing percentage remained unaffected by Moringa supplementation. Regarding blood parameters, rabbits that received MO leaves in their diet showed improvements in red blood cell count, haemoglobin levels, packed cell volume, white blood cell count, neutrophil count, total protein, globulin, and A/G ratio. Moreover, there was a significant decrease in malondialdehyde levels and an increase in glutathione and high‐density lipoprotein levels, indicating an antioxidative effect. Overall, the study concluded that MO leaves supplementation in the rabbit diet positively influenced the rabbits' health by modulating the immune system, improving histological aspects of the intestine, liver, and spleen, and enhancing physiological parameters through its antioxidative properties.

Complementary effects of dapagliflozin and lobeglitazone on metabolism in a diet-induced obese mouse model

Thiazolidinedione, an insulin sensitizer, has beneficial effects on glucose metabolism; however, there are concerns regarding weight gain and heart failure. Sodium-glucose co-transporter 2 (SGLT2) inhibitors can reduce body weight, increase diuresis, and play a protective role in heart failure. We examined the complementary effects of dapagliflozin, an SGLT2 inhibitor, and lobeglitazone, a thiazolidinedione, in high-fat diet (HFD)-induced obese mice. We treated HFD-induced obese mice with vehicle, dapagliflozin, lobeglitazone, and their combination for 12 weeks. Oral glucose tolerance and insulin tolerance tests were performed after 12-week treatment, and body composition was measured by dual-energy X-ray absorptiometry before and after treatment. We analyzed oxygen consumption rate (OCR) using 3T3-L1 cells after treatment of β-hydroxybutyrate and/or lobeglitazone. Treatment with a combination of dapagliflozin and lobeglitazone resulted in a significant decrease in postprandial hyperglycemia compared with dapagliflozin monotherapy, but not compared with lobeglitazone monotherapy. The addition of dapagliflozin to lobeglitazone treatment did not attenuate weight gain compared with lobeglitazone monotherapy in this study. However, this combination prevented the increase of organ weight of liver and heart, and OCR in 3T3-L1 cells was increased after treatment with a combination of β-hydroxybutyrate and lobeglitazone compared to lobeglitazone monotherapy. We confirmed the beneficial effect of lobeglitazone on glucose metabolism; however, we did not find any beneficial effect of dapagliflozin on body weight in HFD-induced obese mice. However, the protective effects of dapagliflozin and lobeglitazone combined therapy on the liver, heart, energy consumption, and β-cell senescence are worth investigating in clinical trials.

Liver impact of growth hormone (GH) intermittent treatment during the growth period in mice.

Liver impact of prolonged GH-treatment given to non-GH-deficient growing mice between the third and eighth week of life was evaluated in both sexes. Tissues were collected 6h after last dose or four weeks later. Somatometric, biochemical, histological, immunohistochemical, RT-qPCR and immunoblotting determinations were performed. Five-week GH intermittent administration induced body weight gain and body and bone length increase, augmented organ weight, higher hepatocellular size and proliferation, and increased liver IGF1 gene expression. Phosphorylation of signaling mediators and expression of GH-induced proliferation-related genes was decreased in GH-treated mice liver 6h after last injection, reflecting active sensitization/desensitization cycles. In females, GH elicited EGFR expression, associated to higher EGF-induced STAT3/5 phosphorylation. Four weeks after treatment, increased organ weight concomitant to body weight gain was still observed, whereas hepatocyte enlargement reverted. However, basal signaling for critical mediators was lower in GH-treated animals and in male controls compared to female ones, suggesting signaling declination.

A new 90-day drinking water study of sodium cyanide in rats to further evaluate National Toxicology Program findings and inform risk assessment.

The National Toxicology Program (NTP, 1993) reported male reproductive effects in a sodium cyanide (NaCN) drinking water study. The critical effect, decreased cauda epididymis weights, was used by U.S. Environmental Protection Agency for their hazard characterization and risk assessment of hydrogen cyanide and cyanide salts. To further investigate potential male reproductive effects, we conducted a new 90-day drinking water study. Our study expanded evaluations of testes and thyroid. Male F344 rats received NaCN in drinking water at 0, 0 (water restricted; paired to top dose), 3, 10, 30, 100, and 300 ppm for 13 weeks, followed by 10-weeks recovery. Plasma thiocyanate increased dose-dependently but returned to baseline during recovery. NaCN caused neither effects on survival, body weight, food consumption, hematology, serum chemistry, urinalysis, thyroid hormones, testes or epididymides weights, sperm motility/viability, sperm morphology, or sperm production; nor clinical, ophthalmic, or histopathologic findings. Increased organ weights in thyroid/parathyroid and liver occurred at 300-ppm but were recoverable. No changes occurred in male reproductive organs. Absent adverse effects, the NOAEL was 300 ppm (21.66 mg/kg/day; highest dose tested). Based on organ weight increases at 300 ppm, the NOEL was 100 ppm (7.46 mg/kg/day).

IMPACT OF DIETARY SUPPLEMENTAL ASCORBIC ACID ON ORGAN WEIGHT, VILLI MORPHOMETRY, ORGANOLEPTIC ATTRIBUTES AND ORGAN HISTOLOGY OF WEANED PIGS

This study aimed at evaluating the impact of dietary supplemental ascorbic acid on organ weight, villi morphometry, organoleptic attributes, and organ histology of weaned pigs using thirty-two Large white-Landrace crossbred with an average weight of 12.32±0.59 kg. The pigs were grouped into four treatments with eight replicates each. Diet C0 was the basal diet (control). Diets C1, C2, and C3 contained the basal diet with 1g/kg, 2g/kg and 3g/kg of ascorbic acid respectively for seven weeks. The weight of liver, kidney, spleen, heart, and lungs were significantly different (p<0.05) with pigs offered ascorbic acid-supplemented diet having higher values. Also, the villus height, villus width and muscle thickness were significantly influenced (p<0.05) with pigs fed diet C3 having the highest value for villus height and width. The organoleptic properties did not differ significantly (p>0.05). The jejunum villi histology showed that pigs fed diets C0 and C1 were essentially normal while those fed diets C2 and C3 had moderate enteritis. No observable lesions were recorded in the structure of the nephron. Moreover, the hepatic histology of pigs fed diet C1 was essentially normal while those fed diets C2 and C3 showed normal hepatocytes but with moderate sinusoidal congestion. It can be concluded that ascorbic acid supplementation caused increased organ weight, aided villus height and width, and reduced muscle thickness with moderate sinusoidal congestion at up to 3g/kg with no deleterious effects on organoleptic attributes.

28-day repeated dose toxicity and toxicokinetics study on new melatonergic antidepressant GW117 in beagle dogs.

GW117 is new melatonergic antidepressant being developed to show better antidepressant action than agomelatine. The purpose of this study was to evaluate the toxicity and to determine potential target organs after oral (gavage) administration of the test article GW117 for 28 days and to assess the reversibility after a 4-week recovery phase in beagle dogs. Toxicokinetics was also evaluated. Four groups were designed in this study, including the vehicle control group and the GW117 50, 150 and 500 mg/kg/day groups, with 5 dogs/sex/group. Body weight, hematology, clinical chemistry, gross necropsy, organ weight, histopathology, and other indicators were examined. Results showed that animals dosed at ≥150 mg/kg/day showed gastrointestinal reactions (watery feces and dark green/red brown feces), with a dose-response relationship in the incidence and severity grade. Female dogs at 500 mg/kg/day had an increase in organ weight and ratios of the liver at the end of the dosing phase. Histopathology examination showed that some animals at 500 mg/kg/day, especially female animals, had minimal centrilobular hepatocyte hypertrophy in the liver, which reversed after 28-day recovery. With the exception of the above, no GW117-related abnormality was noted. Meanwhile, there were no sexual differences in drug exposure and accumulation after the first and last dosing. The no observed adverse effect dose level (NOAEL) was 150 mg/kg/day, under which mean Cmax and AUC0 → t were 583.5 and 2767.0 ng/ml*h for females and 663.2 and 4046.3 ng/ml*h for males on Day 28.

Sequential Pathogenicity Study of SOR+ and SOR- Escherichia coli Isolated from Roasted Meat

The roles of E. coli in cases of diseases has been established and reported to have a substantial degree of morbidity and mortality among children and adults. This study was carried out to investigate the sequential pathogenicity of sorbitol positive (SOR+) and sorbitol negative (SOR-) Escherichia coli isolated from roasted meat in Uli Community. A total of 10 roasted meat samples were randomly collected from four different points in Uli Community and screened for the presence of SOR+ and SOR-E. coli using the pour plate technique. The isolates obtained were characterized and identified using their colonial descriptions, morphological and biochemical characteristics. The pathogenic potentials of the isolates on chicks were investigated by challenging the chicks orally using 0.5 ml of the inoculum (108cells/ml). All chicks were kept under complete observation for 2 weeks for pathological signs and symptoms, mortalities and gross morphological lesions of the internal organs. The SOR+E. coli; T1 (21. 78%), T2 (18. 18%), T3 (26. 73%) and SOR-E. coli R1 (19. 80%), R2 (12. 87%) were seen in the studied samples, and R1 was mostly seen in the samples collected from the school front area. There were a significant (P<0.05) increase in organ weights, obvious pathological signs and lesions on the internal organs of the infected chicks, and these were seen most in SOR-E. coli. There were significant (P<0.05) viable plate counts of the isolates from the harvested organs, of which the counts of SOR-E. coli were recorded most. No count was recorded from non-infected chicks. It was observed that T3 was the most predominant from the studied samples when compared to T1, T3, R1 and R2. The test isolates showed reasonable pathogenic features among chicks and SOR-E. coli, mostly R1 proved to be most pathogenic among the tested isolates.

Regulation of inflammation and COX-2 gene expression in benzo (a) pyrene induced lung carcinogenesis in mice by all trans retinoic acid (ATRA)

AimInflammation provides favourable microenvironment for cancer development. An enhanced COX-2 gene expression is a key inflammatory mediator of cancers and the drug that inhibits it, helps to manage cancer effectively and increases survival rate. The objective is to analyse the inflammatory changes and COX-2 gene expression in benzo (a) pyrene induced mice and to evaluate the regulatory effect of all trans retinoic acid. Materials and methodsThe body and organ weights were recorded in B(a)P induced mice. The haematological parameters and serum inflammatory markers of carcinogenesis were tested. The H & E stained liver and lung tissues were examined for histopathologic changes. The COX-2 gene expression was analysed by RT-PCR and qPCR in lung and liver. Key findingsThe decreased body weight, increased organ weights and the damages in liver and lung were observed in B(a)P induced mice and were prevented significantly upon ATRA treatment. The lowered Hb, RBC and lymphocytes and an enhanced WBC, monocytes and neutrophils observed in B(a)P group were significantly reversed in treated group. A drastic increase in cancer associated inflammatory markers observed in B(a)P induced mice were significantly (P ≤ 0.001) reduced in treated mice. The RT-PCR product density of COX-2 gene was very high in B(a)P group (lung-0.43 ± 0.06; liver-0.39 ± 0.04) significantly lower in treated group (lung-0.12 ± 0.03; liver-0.08 ± 0.03) with a significant difference in RQ values (B(a)P lung-18.46 ± 0.04, liver-12.46 ± 0.08; treated lung-5.93 ± 0.07, liver-2.92 ± 0.10). SignificanceThe ATRA has decreased the inflammatory condition with downregulation of COX-2 gene expression and thereby prevented carcinogenesis during early stage of B(a)P induced cancer development.

Gestational exposure to high fat diets and bisphenol A alters metabolic outcomes in dams and offspring, but produces hepatic steatosis only in dams

The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing worldwide. Perinatal development is a critical window for altered, lifelong health trajectory, and evidence supports the role of perinatal programming in chronic metabolic diseases. To examine the impact of diet and bisphenol A (BPA) on the developmental trajectory of NAFLD in offspring, we exposed dams from pre-gestation through lactation to a human-relevant dose of oral BPA coupled with intake of high fat Western or Mediterranean-style diets. We assessed hepatic steatosis by quantifying hepatic triglycerides (TGs) and metabolic health by measuring body weight, relative organ weights, and serum hormone levels in dams and offspring at postnatal day 10 (PND10) and 10-months of age. In dams, consumption of the Western or Mediterranean diet increased hepatic TGs 1.7–2.4-fold, independent of BPA intake. Among offspring, both perinatal diet and BPA exposure had a greater impact on metabolic outcomes than on hepatic steatosis. At PND10, serum leptin levels were elevated 2.6–4.8-fold in pups exposed to the Mediterranean diet, with a trend for sex-specific effects on body and organ weights. At 10-months, sex-specific increases in organ weight and hormone levels were observed in mice perinatally exposed to Western + BPA or Mediterranean + BPA. These findings suggest lifestage-specific interaction of perinatal exposures to experimental diets and BPA on offspring metabolic health without effects on NAFLD later in life. Importantly, alterations in dam phenotype by diet and BPA exposure appear to impact offspring health trajectory, emphasizing the need to define dam diet in assessing effects of environmental exposures on offspring health.

Sub-acute Toxicity of β-cyfluthrin in Hepatic Tissue and its Amelioration through Punica granatum in Swiss albino mice

β-cyfluthrin, member of synthetic pyrethroid pesticide Type II is broadly used multipurpose insecticide. Widespread and indiscriminate use of β-cyfluthrin leads to environmental contamination and toxicity towards nontarget mammalian systems. The present study was undertaken to examine toxic manifestation of β-cyfluthrin in hepatic tissue of Swiss albino mice and also evaluate possible mitigative potential of pomegranate juice (PJ) in combating pesticide induced hepato-toxicity. Animals were divided into five groups namely, control, vehicle control, Pomegranate juice (PJ) administered, β-cyfluthrin treated and β-cyfluthrin + Pomegranate juice treated groups. β-cyfluthrin (1/20th of LD 50 ) was administered via feeding canula for 21 days. Significant decrease in body weight and increase in organ weight of animals treated with β-cyfluthrin was observed. Various biochemical indices were studied and results obtained revealed altered protein content, cholesterol content, enzyme associated with energy metabolism (ATPase and SDH), ACPase, ALPase and liver marker enzymes (ALT, AST and γ-GT). Co-administration of PJ along with β-cyfluthrin was able to attenuate altered biochemical parameters effectively. Therefore, it is recommended to people associated occupationally with pesticide manufacturing and utilization to include PJ in their diet so as to prevent harmful toxicological effect on various tissues. Keywords : β-cyfluthrin, pyrethroid, biochemical parameters, Punica granatum, hepatotoxicity Cite this Article S. Pal, P. Vaghela, N. Agravat, H.N. Highland, K.R. Desai. Sub-acute Toxicity of β-cyfluthrin in Hepatic Tissue and its Amelioration through Punica granatum in Swiss albino mice. Research & Reviews: A Journal of Toxicology. 2020; 10(3): 41–52p.

Organ Damage due to Elevation of Blood Pressure on NaCl-induced

Introduction: High salt diet is known to induce or aggravate hypertension in hypertensive rats and humans. The elevation of blood pressure by NaCl-induced promotes cardiac hypertrophy, the impairment of left ventricular relaxation, endothelial dysfunction, and kidney injury. This study aimed to examine whether NaCl-induced caused increase blood pressure and weight of organs. Methods: Eight weeks old male Mus musculus were divided to two groups, one group was given NaCl 8% by intraperitoneal injection for 8 hours.Results: Blood pressure was measured previously, in this study systolic and diastolic blood pressure increased significantly (p < 0.05). The increasing of blood pressure was followed by significant increase in organ weight, such as heart and kidney (p < 0.05). Conclusion: This result suggested that NaCl-induced caused hypertension and increased organs weight that may cause early process of damages in organs.

Maternal-fetal outcomes of exercise applied in rats with mild hyperglycemia after embryonic implantation.

Exercise is commonly recommended to control hyperglycemia, including during pregnancy. We conducted this study to understand the potential benefits and risks of exercise during pregnancy of women with diabetes. Specifically, we evaluated the effects of swimming on a diabetic rat during pregnancy and assayed maternal-fetal parameters. Diabetes was induced in the female newborn from Wistar rats by the streptozotocin administration on first postnatal day. At 110 days of life, after confirm mild symptoms of diabetes, the rats were mated and randomly distributed into four experimental groups (minimum of 13 animals/group): Control (C)-nondiabetic animals without swimming; Control and Exercise (CEx)-nondiabetic animals submitted to swimming; Mild Diabetic (MD)-diabetic animals without swimming; Mild Diabetic and Exercise (MDEx)-diabetic animals submitted to swimming. The swimming program was performed from day 7 to 21 of pregnancy. Maternal parameters were evaluated during the pregnancy period. On day 21 of pregnancy, the rats were sacrificed and maternal and fetal parameters analyzed. There are no alterations in body weight, food consumption, water intake, and reproductive outcomes among the groups. The swimming program did not normalize maternal glycemia and other biochemical biomarkers. The diabetes and exercise combination increased organ weight. The fetuses born to these exercising diabetic rats had reduced fetal weight and increased skeletal anomalies (mainly incomplete ossification of sternebra). The intense swimming exercise imposed on female rats during pregnancy impaired maternal metabolic repercussions, contributing to intrauterine growth restriction and fetal skeletal anomalies.

Xylosyltransferase 2 deficiency and organ homeostasis.

In this paper we characterize the function of Xylosyltransferase 2 (XylT2) in different tissues to investigate the role XylT2 has in the proteoglycan (PG) biochemistry of multiple organs. The results show that in all organs examined there is a widespread and significant decrease in total XylT activity in Xylt2 knock out mice (Xylt2-/-). This decrease results in increased organ weight differences in lung, heart, and spleen. These findings, in addition to our previous findings of increased liver and kidney weight with loss of serum XylT activity, suggest systemic changes in organ function due to loss of XylT2 activity. The Xylt2-/- mice have splenomegaly due to enlargement of the red pulp area and enhanced pulmonary response to bacterial liposaccharide. Tissue glycosaminoglycan composition changes are also found. These results demonstrate a role of XylT2 activity in multiple organs and their PG content. Because the residual XylT activity in the Xylt2-/- is due to xylosyltransferase 1 (XylT1), these studies indicate that both XylT1 and XylT2 have important roles in PG biosynthesis and organ homeostasis.

Ameliorative effect of quercetin, catechin, and taxifolin on rotenone-induced testicular and splenic weight gain and oxidative stress in rats.

Background The physiological functions of the testis and spleen can be affected through several cellular and molecular mechanisms such as the generation of reactive oxygen species (ROS) that causes oxidative stress. This study aimed at investigating the protective effect of catechin, quercetin, and taxifolin in rotenone-induced testicular and splenetic toxicity. Methods Male Wistar rats were administered with 1.5 mg/kg rotenone (s.c.) for 10 days followed by post-treatment with catechin (5, 10, or 20 mg/kg), quercetin (5, 10, or 20 mg/kg), and taxifolin (0.25, 0.5, or 1.0 mg/kg) for 3 days (s.c.), followed by estimation of biochemical markers of oxidative stress, inflammatory activities, and tissue damage in testes and spleen. Results Exposure of rats to rotenone caused reduced body weight gain, increased organ weight, decreased glutathione level and activities of glutathione transferase and superoxide dismutase, enhanced lipid peroxidation, and increased activities of prooxidant/proinflammatory enzymes and lactate dehydrogenase, which were mitigated by post-treatment with flavonoids. In general, quercetin and taxifolin showed better activity than catechin. Conclusions Catechin, quercetin, and taxifolin ameliorated rotenone-induced weight disturbances and oxidative damage in rats, indicating their potential relevance in toxicant and pesticide-induced tissue injury.

Organ changes found by postmortem examination in COVID-19 patients

The postmortem study results presented in 20 sources of literature on 186 COVID-19 patients were analyzed. Pathological changes were noted in multiple organs, by involving predominantly the respiratory, circulatory, and excretory systems. The changes in the lungs were characterized by an increase in organ weight (59.3%), a dark red color of the parenchyma (47.4%), compaction of lung tissue (56%), and signs of lung congestion (37.3%). The histological characteristics found during postmortem lung tissue examination, which were indicative of diffuse alveolar damage, were proliferation of type II alveolocytes in 65.2% of cases, the appearance of hyaline membranes lining the alveoli in 64.4%, and interstitial edema in 54.2%. In the analyzed sources, 22% of cases were noticed to have severe thrombosis and pulmonary artery branch embolism that was associated with lower extremity deep vein thrombosis. In all the sources of literature, acute tubular necrosis, tubular luminal dilatation, and interstitial edema were detected in the kidneys.

Oral exposure of rats to dienestrol during gestation and lactation: Effects on the reproductive system of male offspring

This study was aimed at determining whether dienestrol (DIES) affects reproduction in male offspring of rats following oral maternal exposure during gestation and lactation. Pregnant rats were treated from GD 6 to PND 21. Animals received 0 (control-vehicle), 0.75, 1.5, 3.12, 6.25, 12.5, 50, 75 μg/kg bw/d of DIES. A control group -without vehicle-was also included. High DIES concentrations caused abortions at 75 and 50 μg/kg bw/d, while at 12.5 μg/kg bw/d had still miscarriages. Ten male rats per group were kept alive until PND 90 to ensure sexual maturity. Body and organ weights, anogenital distance (AGD) at PNDs 21 and 90, biochemical and sperm parameters like motility, viability, morphology, spermatozoa and resistant spermatid counts, and histopathology for sexual organs and liver were determined. An increase in organ weight (liver and sexual organs) and a decrease in AGD due to vehicle were found. A reduction of sperm motility and viability, and an increase of abnormal sperm morphology were caused by DIES, which provoked a dose-dependent prostatitis. Maternal exposure to DIES induced toxicity on the reproductive system of the male offspring, which could affect the capacity of fertilization.

Hepatic and neuronal phenotype of NPC1−/− mice

Niemann-Pick type C disease (NPC) is a fatal autosomal recessive disorder characterized by a defect in the intracellular transport of lipoproteins leading to the accumulation of lipids in diverse tissues. A visceral and neuronal phenotype mimicking human NPC1 disease has been described in NPC1 mutant mice. These mice are by now the most widely used NPC1 rodent model to study NPC and developmental compounds against this devastating disease. Here we characterized NPC1−/− mice for their hepatic and neuronal phenotype to confirm the stability of the phenotype, provide a characterization of disease progression and pinpoint the age of robust phenotype onset. Animals of 4–10 weeks of age were analyzed for general health, motor deficits as well as hepatic and neuronal alterations with a special focus on cerebellar pathology.Our results show that NPC1−/− mice have a reduced general health at the age of 9–10 weeks. Robust motor deficits can be observed even earlier at 8 weeks of age. Hepatic changes included increased organ weight and cholesterol levels at 6 weeks of age accompanied by severely increased liver enzyme levels. Analysis of NPC1−/− brain pathology showed decreased cholesterol and increased Aβ levels in the hippocampus at the age of 6 weeks. Further analysis revealed a decrease of the cytokine IL-12p70 in the cerebellum along with a very early increase of astrocytosis. Hippocampal IL-12p70 levels were increased at the age of 6 weeks followed by increased activated microglia levels. By the age of 10 weeks, also cerebellar Aβ levels were increased along with strongly reduced Calbindin D-28k levels.Our results validate and summarize the progressive development of the hepatic and neuronal phenotype of NPC1−/− mice that starts with cerebellar astrocytosis, making this mouse model a valuable tool for the development of new compounds against NPC.

Evaluation of the Histomorphological and Toxicological Changes in Rodents after treatment with Hydroethanolic Extract of the Secamone Afzelii Aerial Parts

Objective To evaluate the histomorphological and toxicological changes in rodents after treatment with hydroethanolic extract of the Secamone afzelii aerial parts. Materials and Methods An acute toxicity study on Swiss albino mice of both sexes was performed. Administration of a single dose of 2,000 mg/kg −1 of body weight (bwt) of S. afzelii extract by gavages to 5 mice showed no mortality; hence, a 1/10th dose was used as the highest therapeutic dose. The intra-peritoneal administration produced dose-dependent mortality, with median lethal dose (LD50) being ∼ 281.8 mg/kg −1. In a subacute toxicity study, Wistar rats received daily administration of the extract in the dose range of 50 to 200 mg/kg bwt for 35 days. Its effects on histological, biochemical and hematological parameters were evaluated. Results There was an initial body weight decrease in all the treated animals in the first 7 days. Thereafter, increase in body weight was observed. The treated animals also exhibited organ weight increase when compared with the control. Statistically significant increase (p < 0.05) in aspartate aminotransferase (AST) occurred in the extract treated animals, whereas alanine aminotransferase (ALT) showed a statistically insignificant (p ≥ 0.05) increase when compared with the control. Total plasma protein (TPP) and albumin (ALB) also exhibited insignificant (p ≥ 0.05) increases, while total bilirubin (T. BIL) decreased compared with the control. Insignificant (p ≥ 0.05) changes also occurred in the plasma creatinine and urea levels in the extract treated animals when compared with the control group. The liver tissue histology showed no hepatocellular damage. However, inflammatory changes occurred in the testicular tissue, in which a quantitative decrease in spermatogenic cells was observed due to extensive cellular necrosis, leaving only the basement layer of the seminiferous tubules. Conclusion S. afzelii exhibited a high safety margin, an indication that it is safe for consumption. However, after chronic administration, it caused undesirable effect in the testes that could compromise its fertility function.

Toxicological Assessment of Mineral Hydrocarbons in Foods: State of Present Discussions.

The evaluation of mineral oils by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) provided high acceptable daily intakes for classes largely falling into the mass range strongly accumulated by humans. Because they are roughly 2 orders of magnitude above the present exposure, they authorize strongly increased exposure. An approach based on accumulation seems more adequate. Increased organ weights might be more critical than granulomas. Aromatic hydrocarbons with 1-2 aromatic rings should be distinguished from those with at least 3 aromatic rings. If mineral oil saturated hydrocarbon limits were low, no limit might be needed for the 1-2 ring aromatics. It should be considered to phase out substantial use of mineral oils in food application.