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Tramadol is a popular drug of abuse among adolescent and young adults in many developing African countries due to the opioid agonist properties. We investigated the health implications of the sub-chronic concurrent abuse of tramadol, caffeinated drink and alcohol in adult male Wistar rats. Tramadol was administered at 40 and 20 mg/kg BW respectively, caffeinated drink at 10 ml/kg BW and alcohol at 2 ml/kg BW. The rats were handled such that: group A received distilled water; groups B and C received tramadol and distilled water; groups D and E received tramadol and caffeinated drink; groups F and Greceived tramadol and alcohol; and groups H and I received caffeinated drink and alcohol respectively. The concentrations of nitric oxide (NO), reduced glutathione (GSH),malondialdehyde (MDA),protein carbonyl (PC),protein thiol (PT), interleukin 1β (IL-1β), vascular cell adhesion molecule (VCAM-1), monocyte chemotactic protein-1 (MCP-1), oxidized low density lipoprotein cholesterol (ox-LDLC), and activities of paraoxonase (PON-1) and acetylcholine esterase (ACE) were determined. Histo-pathological analysis was performed on the liver, kidney, brain and small intestine. The concentrations of blood nitric oxide, GSH and MDA increased (p0.05). Inconsistent alterations were obtained in blood PON-1 activities across the groups. Decreases were recorded in the GSH and TPT in the liver and brain with increases in PC and MDA (p

Introduction: Erythrophleum Ivorense (EI) is a tree found across tropical Africa. The bark of EI is widely used as hunting poisons for animals and ordeal poison in humans. Eating this plant causes paralysis, respiratory distress, and amnesia. In folklore, these behavioral changes have been attributed to guilt in victims; nonetheless, no scientific evidence supports this claim. Thus, the mechanism of neurotoxicity and behavioral alteration of this plant should be investigated. Methods: A total of 48 BALB/c male mice were randomly divided into four groups. The three experimental groups were administered an aqueous extract of EI in a single daily dose of 5, 10, and 15 mg/kg bodyweight for 28 days, while the control group received distilled water. Afterward, the motor coordination, learning, memory, and grip strength of the mice were accessed with wire grip, Morris water maze, and inverted wire mesh grid grip tests. Histological staining of brain sections was also carried out. Results: At all tested doses, the aqueous extract of EI caused a significant reduction in hanging latency, significantly increased escape latency, and decreased duration of the target platform in the Morris water maze test compared to control. Reduced grip strength was also observed in the test groups compared to the control. Histology revealed dysmorphic and disoriented Purkinje cells and loss of this cell layer of the cerebellum. Conclusion: Erythrophleum ivorense administration altered motor coordination, learning and memory, and grip strength in mice dose-dependently. It also caused disruption of granule cells layer, loss of Purkinje cells, and altered cerebellar anatomy leading to motor deficits in mice.

Aim: This study was aimed at evaluating the impact of Coenzyme Q10 on hormonal profile in male Sprague-Dawley rat exposed to sub-chronic concentrations of Cypermethrin. Experimental Design: A completely randomized experimental design using standard methods for analysis. Hormonal assay was carried out by Microplate Enzyme Immunoassay using their respective test kits. Including AccuBindTM Microplate EIA Test system from Monobind Inc. Lake Forest CA 92630 USA while statistical analysis was carried out using one-way Analysis of Variance (ANOVA); where significant differences were found, Pair-wise comparisons conducted with Tukey test using SPSS 20 software. Location and Duration of Study: This study was carried out in the Department of Biology, Ignatius Ajuru University of Education Rumuolumeni, Port Harcourt, Rivers State, Nigeria. GPS 4o48ʹ14ʹʹ N 6o59ʹ12ʹʹ E. The study lasted for 28days. Methodology: Thirty male Sprague-Dawley rats were randomly assigned to five groups, A-E(n=6/group).Group A was given cool clean water and standard rat pellet ad libitum. Group B,C and D were administered Cypermethrin @ 10mg/kg/bw,20mg/kg/bw,30mg/kg/bw respectively along with 10mg/kg/bw of coenzyme Q10 (CoQ10). Group E received 30mg/kg/bw of cypermethrin only without Coenzyme Q10. All animals were allowed access to cool clean water and standard rat pellet ad libitum. Bodyweight of the animals were taken twice a week and recorded in grams. Twenty-four hours before the animals were euthanized with ethyl ether inhalation, feed was withdrawn from the animals. Blood samples were collected by cardiac puncture between the hours of 7:00 and 9:00am into plain sample tubes according to the approved protocol of blood collection techniques. Analysis for the quantitative determination of all androgens was by Microplate Enzyme Immunoassay using the AccuBindTM Microplate EIA Test system from Monobind Inc. Lake Forest CA 92630 USA and expressed as their respective units. The animals were latter dissected and the vital organs harvested and weighed. The values were subjected to statistical analysis using SPSS software 20. Results: Results showed that there was no significant difference between the bodyweight and organ weight of animals in the treatment group compared with the control. Also, treatment with Cypermethrin only in group E, reduced the level of all the androgens considered in exposed animals. However, with concurrent administration of coenzyme Q10, the production of all androgens especially the production of Follicle Stimulating Hormone, Luteinizing Hormone and Progesterone in groups B,C,D and Estrogen in group B were significantly (P=.05) increased to values higher than the control. Conclusion: This elevation indicates the role of Coenzyme Q10 as an effective antioxidant to boost hormonal level production especially the level of androgens.

Background and Objective: Data from researches have shown a rise in disease, ill health and death linked with the utilization of herbal products, thereby raising global awareness in the last few years. On that account, the safety and toxicity evaluations of herbal products and preparations was essential. This study evaluated the toxicological profile of Yagari – a herbal mixture. Materials and Methods: Acute oral toxicity (LD50) was carried out in Swiss mice according to Lorke’s method while sub-chronic toxicity study was carried out with 20 adult albino rats which were divided into 4 groups of 5 animals each. Group one served as control and received normal saline while Groups 2 to 4 received 250, 500 and 1000 mg/kg yagari respectively for 28 days. The body weights of the rats were monitored while on day 29, the rats were sacrificed and blood samples and organs were collected for biochemical/hematological analysis and histopathological examination respectively. Results: Results showed that Yagari is not noxious up to 5000 mg/kg following acute oral toxicity study. The sub-chronic toxicity test divulged that Yagari had no serious end results on the biochemical, hematological and histopathological parameters, although the body weight of the animals significantly increased. Conclusion: It was concluded that Yagari is not toxic, still further investigations on a large number of animals are essentially needed to denote safety and efficacy of the herbal formulation.

Background Morus alba L. fruits are consumed since long for their nutritional and medicinal values. Although there were studies on the neuroprotective activity of the fruit extract, safety profile of the fruit extract is not yet explored as per the recommended standard guidelines over the central nervous system (CNS). The present work was aimed to assess the neurotoxicity profile of chemically characterized extract of M. alba L. fruits (MA) using validated OECD guidelines, i.e., 425 and 424 in rodents. Results Neurobehavioural parameters were examined for motor, sensory and behavioural responses using actophotometer, hot plate and light and dark box test, respectively as per OECD 424. Interestingly, no sign of mortality and/or adversity on mice treated per-orally with MA (2000 mg/kg) was observed during the limit test as per OECD 425. Further, rats treated with MA (1000, 300 and 100 mg/kg, p.o.) for 28 days, showed insignificant (p < 0.05) changes in body weight, food consumption, neurobehavioural responses, organ weights and biochemical, haematological and histopathological features when compared with vehicle-treated animals. Conclusion The outcome of findings suggests that MA is safe in acute oral as well as sub-chronic (28 days) administration in mice and rats respectively. MA (1000 mg/kg) did not pose any toxic sign and symptoms on neurobehavioural responses in rats even after 28 days repeated treatment in compliance with OECD 424.

Myopia (nearsightedness) is a vision disorder with a blurring of far objects, affect millions worldwide. 7-methylxanthine (7-MX) is a molecule that is presently under clinical investigation for the treatment of myopia. In the present study, we have investigated sub-chronic and chronic toxicity of 7-MX in comparison to other clinically used methylxanthines i.e., caffeine and theobromine as per OECD guidelines 408 and 452. 7-MX was administered orally for 90 days at three different doses of 250, 500, and 1000 mg/kg for sub-chronic toxicity evaluation, and at a limit dose of 1000 mg/kg in 180 days chronic toxicity evaluation in rats. In sub-chronic treatment, 7-MX showed no mortality and signs for toxicity in any group, whereas 10% and 40% mortality with signs for toxicity were observed in caffeine and theobromine treated groups, respectively. A similar, safety profile was observed with 7-MX in 180 days of chronic toxicity study. Further, to confirm any morphological changes in organs; ultrasound and X-rays analysis were performed and no changes in the size of organs, cyst formation, fluid retention, or crystal formation was observed. Thus, the repeated dose study of 7-MX for 180 days may augment the possibility of using 7-MX clinically for the safe and effective treatment of myopia.

Khat, Catha edulis, use is rampant in Eastern Africa and Middle East countries with associated reports of reproductive function impairment in the body of the user. Reports on recovery post long-term khat exposure are obscure. The present study investigated evidence of restoration of testicular and epididymal structure and function during withdrawal from cytotoxic damage caused by sub-chronic exposure of khat extract. Twenty-eight male rabbits were divided into 7 groups of 4 rabbits each. Group I (control) was administered normal saline while groups II, III and IV were administered 1.0 g/kg, 10 g/kg and 20 g/kg body weight of khat extract, respectively, via oral gavage on alternate days of the week for 12 weeks. Blood samples from animals were collected for hormonal assays followed by euthanasia using 26.4 mg/kg body weight of Sagatal sodium intramuscularly for testicular and epididymal histology. Group V, VI and VII were administered 1.0 g/kg, 10 g/kg and 20 g/kg body weight of khat extract, respectively, orally on alternate days of the week for 12 weeks followed by 1-month withdrawal period, blood samples collected for hormone assays and animals sacrificed for testicular and epididymal histology. High khat dose, 20 g/kg body weight, at sub-chronic exposure caused degeneration in spermatogenic cells with accompanying decrease in plasma FSH and testosterone. Histological output of Sertoli cells, Leydig cells and epididymal epithelium appeared unaffected in treatment groups. Post withdrawal data showed apparent regeneration of seminiferous epithelium and restoration of plasma FSH and testosterone comparable to control. It appears khat extract preferentially affected germ cell spermatogonia and subsequent daughter cells while stem cell spermatogonia were unaffected and contributed to regeneration of germinal epithelium and endocrine function.

Repeated-dose toxicity (RDT) is a critical endpoint for hazard characterization of chemicals and is assessed to derive safe levels of exposure for human health. Here we present the first attempt to model simultaneously no-observed-(adverse)-effect level (NO(A)EL) and lowest-observed-(adverse)-effect level (LO(A)EL). Classification and regression models were derived based on rat sub-chronic repeated dose toxicity data for 327 compounds from the Fraunhofer RepDose database. Multi-category classification models were built for both NO(A)EL and LO(A)EL though a consensus of statistics- and fragment-based algorithms, while regression models were based on quantitative relationships between the endpoints and SMILES-based attributes. NO(A)EL and LO(A)EL models were integrated, and predictions were compared to exclude inconsistent values. This strategy improved the performance of single models, leading to R2 greater than 0.70, root-mean-square error (RMSE) lower than 0.60 (for regression models), and accuracy of 0.61-0.73 (for classification models) on the validation set, based on the endpoint and the threshold applied for selecting predictions. This study confirms the effectiveness of the modeling strategy presented here for assessing RDT of chemicals using in silico models.

Aim: In this study, the methanol stem bark extract of Detarium microcarpum was evaluated for sub-chronic, biochemical and histopathological studies. Methodology: Sub-chronic toxicity studies was investigated in rats administered with 35, 70 and 140 mg/kg doses of the extract orally for 28 days using standard laboratory procedures after the acute toxicity was carried out. Results: The median lethal dose (LD50) of the extract was calculated to be equal to (≥) 5000 mg/kg body weight in rats orally. Serological studies revealed significant (p

There is little data available for the toxicity of used aircraft engine oils relative to their unused (new) versions. This study was conducted to determine if grade 3 (G3) and 4 (G4) aircraft engine oils in their new states (G3-N and G4-N) and their used versions (G3-U and G4-U) have the potential to induce toxicity via dermal application. Male and female Sprague Dawley rats were dermally exposed to water (control), new and used versions of G3 and G4 oils to determine the oil sub-chronic toxicity potentials. A volume of 300 μL of undiluted oil was applied to the pad of the Hill Top Chamber System©. Then the chamber was attached to a fur-free test site located at the back of the rat for 6 h/day for 5 consecutive days/week for 21 days (15 total exposures). Recovery rats also received similar treatments and were kept for 14 days post-exposure to screen for reversibility, persistence, or delayed occurrence of toxic effects. Both G3 and G4 oils had a significant impact on the weight of male and female reproductive organs: testes weights for recovery rats exposed to G3-N significantly decreased (12%) relative to controls; G3-N and G3-U decreased uterus weights by 23% and 29%, respectively; G4-N decreased uterus weights by 32% but were resolved at the end of the recovery period; G4-N increased the weight of the adrenals and spleen for females by 34% and 27%, respectively, during the recovery period. G3 and G4 induced more changes in female blood indices than in those for males. Of all versions of oils, G4-N induced the most changes in profiles of female blood. G4-N significantly decreased the white blood cells, lymphocytes, neutrophils, eosinophils and increased the mean platelet volumes. Interestingly, males were not affected by exposure to G4-N oil. While G3-N decreased the white blood cells and lymphocytes for females it slightly increased those for males. In summary, G3 and G4 oils impacted the weights for male and reproductive organs. This study highlights the health risks that aircraft maintenance workers may be exposed to if precautions are not taken to minimize exposure to these oils., Graphical abstract Unlabelled Image, Highlights • Grade 3 and grade 4 aircraft engine oils contain organophosphate compounds. • Dermal exposure to these oils impacted organ weights of female and male rats. • Unused versions of these oils had more effects on blood indices than used versions. • Females may be more susceptible to exposure to these oils than males.

To assess nephropathic potential of Caladium bicolor methanolic extract within the renal parenchyma of experimental Wistar rats. Twenty four albino Wistar rats (weighing between 180-195 g) were divided into four groups which include Group I treated with distilled water (2 ml/kg b.w.), Group II treated with methanolic extract of C. bicolor (100 ml/kg b.w.), Group III treated with methanolic extract of C. bicolor (200 ml/kg b.w.), Group IV treated with methanolic extract of C. bicolor (300 ml/kg b.w.). All administrations were done orally and once daily for a period of thirty five days. Body weight of animals was recorded during days 0, 7, 14, 21, 28 and 35 of study. After the study period, kidney tissue of study animals was harvested, weighed and processed for histopatho logical study. Staining of renal tissue sections was done using H & E technique, examined under microscope for observable histopathological changes that were scored using image-J software. Results of this study showed that sub-chronic exposure to methanolic extract of C. bicolor caused reduction in body and renal tissue weight. Moreover, exposure to the extract increases significantly (p < 0.05) renal histopatho logical changes including inflammation, necrosis, glomerular congestion and tubular dilatation within the renal parenchyma of study animals. Therefore, methanol extract of C. bicolor exhibited dose-independent nephropathic effect on the renal parenchyma following a sub-chronic exposure in experimental Wistar rats.

Seaweeds are known to be rich source of micronutrients and bioactive compounds. The main objective of this study was to find the toxicological evaluation and heavy metal accumulation of five under-exploited edible seaweeds in animal model followed by dosage determination for regular consumption as a food by humans and food application. Some under-exploited seaweeds like Acanthophora spicifera, Gracilaria edulis, Padina gymnospora, Ulva fasciata and Enteromorphoa flexuosa were selected forthis study. The ED50 study was conducted in Wistar strain rats for 90 days with single dose administration of seaweed extract of 2000 mg/kg/BW. At the end of 90th day rats were euthanized, serum of the rats examined for biochemical, haematological, liver enzymes, and vital organs were dissected out for heavy metal analysis and urine samples collected intermediary to analyse electrolyte minerals. Result showed that no-observed adverse effect level (NOEL) on five seaweeds, did not cause any death and no significant variation in biochemical and haematological parameters, the values were found within standard values. Locomotor activity suggests normal action, organ necropsy showed no histopathology lesions, regular cell alignment in the tissue cross section. Heavy metals like arsenic, lead were found in trace amount and no mercury accumulation found in kidney, liver and brain of rats. Therefore, these five seaweeds were safe for human consumption and also for food product developement. Keywords: Seaweed, Sub-chronic toxicity, Acanthophora spicifera, Gracilaria edulis, Padina gymnospora, Ulva fasciata, Enteromorphoa flexuosa

To decrease the Vicia faba beans cooking time, some chefs added ethylene diamine tetra-acetic acid (EDTA) during the cooking process. This study addressed the effect of sub-acute and chronic administrations of faba bean's cooking media containing EDTA (C.M./EDTA) on hepato-renal functions in mice. Ninety male mice were divided into three groups (n = 30). The group 1 (Gp1) divided into Gp1a and Gp1b, both were served as control for sub-acute and sub-chronic treatments. Gp2 divided into Gp2a and Gp2b then administered with 200 µl of C.M. for 15 and 90 days, respectively. Gp3 divided into Gp3a and Gp3b then administered 200 µl of C.M./EDTA (10 mg/kg) for 15 and 90 days, respectively. Hematological, biochemical, and histopathological alterations were investigated. The results showed that sub-acute administration of C.M./EDTA did not show any signs of toxicity, however, sub-chronic administration showed substantial toxicity evidenced by alterations in some biochemical and histological investigations.

Macrophages are a heterogeneous population with both pro- and anti-inflammatory functions play an essential role in maintaining tissue homeostasis, promoting inflammation under pathological conditions, and tissue repair after injury. In pulmonary hypertension, the M1 phenotype is more pro-inflammatory compared to the M2 phenotype, which is involved in tissue repair. The role of macrophages in the initiation and progression of pulmonary hypertension is well studied. However, their role in the regression of established pulmonary hypertension is not well known. Rats chronically exposed to hemoglobin (Hb) plus hypoxia (HX) share similarities to humans with pulmonary hypertension associated with hemolytic disease, including the presence of a unique macrophage phenotype surrounding distal vessels that are associated with vascular remodeling. These lung macrophages are characterized by high iron content, HO-1, ET-1, and IL-6, and are recruited from the circulation. Depletion of macrophages in this model prevents the development of pulmonary hypertension and vascular remodeling. In this study, we specifically investigate the regression of pulmonary hypertension over a four-week duration after rats were removed from Hb + HX exposure with and without gadolinium chloride administration. Withdrawal of Hb + HX reversed systolic pressures and right ventricular function after Hb + Hx exposure in four weeks. Our data show that depleting circulating monocytes/macrophages during reversal prevents complete recovery of right ventricular systolic pressure and vascular remodeling in this rat model of pulmonary hypertension at four weeks post exposure. The data presented offer a novel insight into the role of macrophages in the processes of pulmonary hypertension regression in a rodent model of Hb + Hx-driven disease.

Background:Cadmium is a heavy metal that can cause various injuries in the body, including nephrotoxicity. L-Arginine is a metal chelator that can prevent oxidative damage caused by oxygen free radicals. Objectives:This study aimed to investigate the effect of L-arginine in inhibiting mitochondrial toxicity induced by subchronic cadmium exposure in the kidney of male mice. Methods: A total of 42 male mice were randomly divided into six groups (n=6): control (normal saline), cadmium (2 mg/kg), cadmium (2 mg/kg) plus three doses of L-arginine (50, 100, and 200 mg/kg) and finally cadmium (2 mg/kg) plus vitamin C (500 mg/kg). After 42 days, the animals were anesthetized with ketamine/xylazine. Their kidney tissues were removed, and mitochondrial fractions were isolated. Oxidative stress factors and mitochondrial damage parameters (MTT, swelling, and mitochondrial membrane potential) were measured in renal isolated mitochondria. Also, evaluation of Blood Urea Nitrogen (BUN) and Creatinine (Cr) tests were done. Results: Significant rise in BUN and Cr were observed in cadmium-treated mice (P

Avocado paste (AP) is a phenolic-rich byproduct of avocado oil extraction. The effects of sub-chronic consumption of diets supplemented with an AP phenolic extract (PE) were analyzed. A standard diet (SD), high-fat diet (HFD), and these supplemented with PE (SD + PE and HFD + PE) were used. Significantly increased satiety was observed in PE-supplemented groups, according to less food consumption (-15% in SD + PE vs. SD, and -11% in HFD + PE vs. HFD), without changes in weight gain or percentage of adipose tissue. PE-supplemented groups had an increased plasma concentration ( + 16% in SD + PE vs. SD, and +26% in HFD + PE vs. HFD) and relative mRNA expression (+74% in SD + PE vs. SD, and +46% in HFD + PE vs. HFD) of GLP-1; an increase in plasma leptin and adiponectin was independent of their mRNA expression. Our results suggest that AP-derived PE exerts a satiety effect in vivo, possibly mediated by GLP-1, leptin, and adiponectin. PRACTICAL APPLICATIONS: Minimizing food waste is a top priority in most of the world, thus, researchers seek methods to reintroduce industrial fruit and vegetable byproducts into the food processing chain. The present work highlights the potential of avocado byproducts as sources of bioactive phenolic compounds, whose sub-chronic consumption (8 weeks) exerts a satiety action in vivo. Avocado farming is resource-intensive, making it of relevance to producers and processing industries to avoid discarding its byproducts as much as possible.

Solanum incanum Linn. (Solanaecae) is used for its medicinal and nutritional values in parts of tropical Africa, including Northeast of Nigeria. The present study evaluated acute and sub-chronic oral toxicities of S. incanum fruit extracts in Swiss albino mice. The fruits were extracted by cold maceration method using distilled water and ethanol as solvents.

The objective of the present study was to evaluate the safety of long term consumption of ethanolic fraction of Neurocalyx calycinus leaves (NCEF) in rodents. The NCEF was subjected to detect the presence of various phytoconstituents. In acute oral toxicity study, graded doses of NCEF was administered in mice and were observed up to 14 days. In sub-chronic oral toxicity study, NCEF was administered to Wistar rats at doses of 50, 500 and 1000 mg/kg b.w. per day for 90 days and after that, observed up to 28 days. NCEF showed the presence of alkaloids, steroids, phenolics and glycosides. In acute toxicity study, there was no mortality and no behavioural signs of toxicity at the highest dose level (6400 mg/kg b.w.). In sub-chronic oral toxicity study, there were no significant difference observed in the consumption of food and water, body weight and relative organ weights. Haematological, serum biochemical, hepatic oxidative stress marker analysis and urine analysis revealed the non-adverse effects of prolonged oral consumption of NCEF. The histopatho-logic examination did not show any differences in vital organs. Based on our findings, NCEF, at dosage levels up to 1000 mg/kg b.w., is non-toxic and safe for long term oral consumption.

The aim of present study was to assess the genotoxic effects of endocrine-disrupting compounds 4-nonylphenol (NP) on Channa punctatus after sub chronic exposure. Blood cells from gill and kidney were used for the study and micronucleated cell (MNC) and aberrant cell (AC) frequencies were used as biological indicators. The exposure was given to C. punctatus for 90 days, and the effect was seen after 30, 60, and 90 days of exposure. Three sublethal concentrations were decided after calculating the safe application rate. Exposure resulted in increased frequency of MNC and AC in both the tissues. Gill tissue was found to be more sensitive to 4-nonylphenol exposure. Highest MNC and AC frequency was found at 90 days of exposure in gill tissue and the values were 4.45±0.28 and 63.71±0.84 respectively. After exposure for 90 days, post-30 days recovery was also studied and we found a significant reduction (p?0.01) in the values of both the parameters showing a great capacity of C. punctatus to restore its DNA integrity.

Taraxacum officinale (T. officinale) is a leafy vegetable that is commonly used traditionally as a diuretic agent. In the current study, we aimed at exploring the potential antihypertensive effect ...

Cadmium (Cd) is a ubiquitous non-essential environmental and industrial toxicant that affects various organs in humans and experimental animals. Robust evidence confirms the contribution of oxidative stress to the pathogenesis of Cd-induced hepatic damage. Potent polyphenols found in virgin coconut oil (VCO) are free radical scavengers that may be beneficial against Cd hepatotoxicity. Thus, we aimed to evaluate the possible protective effect of polyphenols isolated from VCO on Cd-induced hepatotoxicity and oxidative stress in rats. Rats were pretreated with polyphenols isolated from VCO (10, 20, and 50 mg/kg, orally) 2 weeks prior to concurrent Cd administration (5 mg/kg, orally) for 5 weeks. Subsequently, liver damage, hepatic oxidative stress, and histopathological alterations were evaluated.

Due to ingestion of contaminated foods, the human gastrointestinal tract is the most likely site of exposure to microplastics (MPs) with gut barrier dysfunction and intestinal inflammation. Aimed to assess the effects induced by MPs with different granulometry (polystyrene (PS) 3 and 10 µm), we performed an in vitro study by using the human intestinal cell line HT29. As a novelty, we assessed the sub-chronic exposure extending the treatment up to 48 days simulating the in vivo situation. In the range of 100–1600 particles mL−1, both the PS suspensions had moderate cytotoxicity after 24 h with percentages of mortality between 6.7 and 21.6 for the 10 µm and 6.1 and 29.6 for the 3 µm PS. Microscopic observation highlighted a more pronounced lysosomal membrane permeabilization in HT29 exposed to PS 3µm. Reactive oxygen species production was higher in cells exposed to PS 10 µm, but sub-chronic exposure highlighted the ability of the cells to partially neutralize this effect. Comet-assay confirmed the temporary oxidative damage that was PS-induced. Overall, considering the very fast turnover of intestinal cells, the increase in cell mortality, equal to 25% and 11% for 3 and 10 µm PS-MPs for each time point, could trigger intestinal disorders due to prolonged exposure.

Cadmium is one of the major environmental pollutants associated with an increment in industrial and urbanization activities. It has health consequences when it reaches the human diet through the soil, water, and plant. Chronic exposure to cadmium has a serious effect on human health. It accumulates mainly in the liver and the kidney. In addition, it can accumulate in the different organs and tissues and exert its toxic effect on the body. Data generated from animal studies reported that elevated levels of cadmium in the blood lead to cardiovascular complications. Cardiac myosin-binding protein C (cMyBP-C) is associated with the myosin thick filament and is involved in cross-bridges cycling and regulation of muscle contraction. It is a reliable marker to indicate the status of cardiac contractility. Therefore, this study is carried out to investigate the effect of cadmium on levels of cMyBP-C during chronic cadmium toxicity. Male Sprague Dawley rats were subjected to a daily cadmium chloride dose (15ppm/Kg of body weight) for a period of 10 weeks. Then heart samples were collected and both gene and protein expression of cMyBP-C were analyzed. The data demonstrated that cadmium decreased cMyBP-C at the protein level and downregulated its expression at the gene level. Therefore, cMyBP-C can be used as a potential biomarker for cadmium cardiotoxicity

Synthetic amorphous silica (SAS) consists of agglomerates and aggregates of primary particles in the nanorange (

Iron oxides are Group 3 (not classifiable as to its carcinogenicity to humans) according to the International Agency for Research on Cancer (IARC). Occupational exposures during iron and steel founding and hematite underground mining as well as other iron predominant exposures such as welding are Group 1 (carcinogenic to humans). The objective of this study was to investigate the potential of iron as iron (III) oxide (Fe(2)O(3)) to initiate lung tumors in A/J mice, a lung tumor susceptible strain. Male A/J mice were exposed by oropharyngeal aspiration to suspensions of Fe(2)O(3) (1 mg) or calcium chromate (CaCrO(4); 100 μg; positive control) for 26 weeks (once per week). Shams were exposed to 50 μL phosphate buffered saline (PBS; vehicle). Mice were euthanized 70 weeks after the first exposure and lung nodules were enumerated. Both CaCrO(4) and Fe(2)O(3) significantly increased gross-observed lung tumor multiplicity in A/J mice (9.63 ± 0.55 and 3.35 ± 0.30, respectively) compared to sham (2.31 ± 0.19). Histopathological analysis showed that bronchiolo-alveolar adenomas (BAA) and carcinomas (BAC) were the primary lung tumor types in all groups and were increased in the exposed groups compared to sham. BAC were significantly increased (146 %) in the CaCrO(4) group and neared significance in the Fe(2)O(3) group (100 % increase; p = 0.085). BAA and other histopathological indices of toxicity followed the same pattern with exposed groups increased compared to sham control. In conclusion, evidence from this study, in combination with our previous studies, demonstrate that exposure to iron alone may be a potential risk factor for lung carcinogenesis.

Rationale In rodents, acute haloperidol treatment induces psychomotor impairments known as catalepsy, which models akinesia in humans and is characterized as an animal model of acute Parkinsonism, whereas sub-chronic haloperidol reduces exploratory behavior, which resembles bradykinesia. Haloperidol-induced catalepsy in rats can be ameliorated by playback of 50-kHz ultrasonic vocalizations (USV), an emotionally and motivationally relevant appetitive auditory stimulus, representing an animal model of paradoxical kinesia. In a condition like PD where patients suffer from chronic motor impairments, it is paramount to assess the long-term symptom relief in an animal model of Parkinsonism. Objectives We investigated whether 50-kHz USV playback ameliorates psychomotor deficits induced by haloperidol in a sub-chronic dosing regimen. Methods In phase 1, distance traveled and number of rearing behavior were assessed in an activity chamber in order to investigate whether sub-chronic haloperidol treatment induced psychomotor impairments. In phase 2, we investigated whether 50-kHz USV playback could overcome these impairments by assessing exploratory behaviors and approach behavior towards the sound source in the 50-kHz USV radial maze playback paradigm. Results Sub-chronic haloperidol treatment led to psychomotor deficits since the distance traveled and number of rearing behavior were reduced as compared to saline control group or baseline. These psychomotor impairments were ameliorated during playback of 50-kHz USV, with haloperidol treated rats showing a clear social approach behavior towards the sound source exclusively during playback. Conclusions This study provides evidence that 50-kHz USV playback induces paradoxical kinesia in rats exhibiting motor deficits after sub-chronic haloperidol, as we previously showed after acute haloperidol treatment.

In the present study, we determined the 24, 48, 72, and 96 h LC50 values for a glyphosate- based commercial herbicide (GBH) for the aquatic snail Melanopsis praemorsa. We examined subacute toxicity responses from M. praemorsa after 30-day exposure to 1/10, 1/5, and 1/2 of the 96 h LC50 value using several biochemical markers. Glutathione reductase (GR) and glutathione S-transferase (GST) activities were significantly inhibited when compared to control after 4 days of GBH exposure. On the twentieth day of exposure, GST and GR activities were inhibited in organisms exposed to both LC50/10 and LC50/5 compared to control. These results showed that chronic GBH exposure inhibited GST, an important detoxifying enzyme. GR, an important oxidative stress marker, was likely inhibited as a result of inhibition of the detoxification mechanism.

According to the WHO, about 3 million people die each year due to ambient air pollution. Most of the in vivo studies on the PM 2.5 effects have been done on respiratory and cardiovascular tissues. However, little is known about the effects on the tissues involved on xenobiotic removal, such as kidneys. In the present study we assess the harmful effects of sub-chronic exposure to PM 2.5 on the kidney, by investigating histologic and serum alterations in healthy and hypertensive rat models. Mean PM 2.5 concentrations during exposures were slightly above the daily WHO standard. Exposed animals showed fibrosis, mesangial expansion, decrease glomerular and tubular lumen volumes in kidneys, with an elevated BUN. Hypertensive animals also exhibited much more severe alterations than healthy animals. We conclude that PM 2.5 induces minimal or small-scale abnormalities that can be determinant for renal health preservation. Fil: Tavera Busso, Iván. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina Fil: Mateos, Ana Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina Fil: Juncos, Luis Isaias. Fundación J. Robert Cade; Argentina Fil: Canals, Norma. Oulton-inst D/diag y Tratamiento Ambulatorio; Argentina Fil: Carreras, Hebe Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina

The aim of this study was to elucidate the protective effect of glycyrrhizin on diazinon-induced changes in body and organ weights, blood hematology, lipid profile, biochemistry parameters and tissue markers of oxidative stress in male Wistar rats over a 7-week period. Rats were orally given sublethal dose of diazinon (10 mg/kg daily; 0.008 LD50), while glycyrrhizin (25 mg kg