Administration Of Pb Research Articles

Biomimetic liposome amplifying mitochondrial damage to potential cancer radio-immunotherapy

Radiotherapy, despite its precision and non-invasiveness, often fails due to the resistance of cancer stem cells (CSCs), which are characterized by high self-renewal capabilities and superior DNA repair mechanisms. These cells can evade RT and lead to tumor recurrence and metastasis. To address this challenge, a novel delivery system named PB has been introduced. This system combines liposomes with platelet membranes to encapsulate Bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl) ethyl sulfide (BPTES), thus enhancing its delivery and release specifically at tumor sites. In addition, this system not only targets CSCs effectively but also increases the local concentration of BPTES upon X-ray irradiation, which reduces glutathione levels in tumor cells, thereby increasing oxidative stress and damaging mitochondria. PB-elicited mitochondrial damage as the STING signal initiator, which mediated significant upregulation in the expression of a cGAS-STING pathway-related protein thereby amplifying the STING signal. Systemic intravenous administration of PB remarkably promoted DC maturation and CD8+ T cell infiltration, thus eliciting strong antitumor effects. Overall, this PB system presents a potent method to overcome CSC-related resistance and offers a promising approach for future cancer treatment protocols.

Impact of Moringa oleifera leaf extract in reducing the effect of lead acetate toxicity in mice

This study aimed to assess the impact ofMoringa oleifera(M. oleifera) leaf extract against the poisoning of lead acetate; therefore, sixty mice were allocated into 4 groups with 15 in each, as G1) blank control, G2) supplied with 300 mg/kg body weight (BWT).M. oleiferaextract, G3) supplied with 60 mg/kg BWT of lead acetate [Pb(C2H3O2)2], and G4) supplied with extract ofM. oleifera + lead acetate. The liver enzymes were elevated post-treatment with Pb(C2H3O2)2, which then lowered to almost the normal level whenM. oleiferawas supplied to mice previously treated with Pb(C2H3O2)2. The values in (G3) decreased when compared with G1 (92.33 ± 12.99, 21.67 ± 2.91 and 98.00 ± 13.20 U/L, respectively. Also, the cholesterol and low-density lipoprotein levels were elevated post-supplementation withM. oleiferaand Pb(C2H3O2)2. Pb(C2H3O2)2 improves the lipid profile, whereas M. oleifera pretreatment reduced cholesterol (CHOL), high density low cholesterol (HDL-c), and low-density low cholesterol (LDL-c) levels in animals fed Pb(C2H3O2)2. Pb(C2H3O2)2 elevates the total protein but lowers the total bilirubin and triglycerides postM. oleiferatreatment and Pb(C2H3O2)2 when contrasted with G1. The protective effect of M. oleifera was caused by the fact that it lowered triglycerides (TG) and total bilirubin (TBIL) and raised total protein (TP). After administration of Pb(C2H3O2)2, the histological examination revealed alterations in the hepatocytes and kidneys of G3. Also, the liver and kidney cells in mice supplied withM. oleiferaafter Pb(C2H3O2)2 poisoning recovered. In conclusion, Pb is toxic, and the usage ofM. oleiferapartially enhances the negative impacts induced by Pb(C2H3O2)2.

The antiinflammatory and antifibrotic effect of olive phenols and Lactiplantibacillus plantarum IMC513 in dextran sodium sulfate–induced chronic colitis

Objectives: After a chronic intestinal injury, several intestinal cells switch their phenotype to activated myofibroblasts, which in turn release an abnormal amount of extracellular matrix proteins, leading to the onset of the fibrotic process. To date, no resolutive pharmacological treatments are available, and the identification of new therapeutic approaches represents a crucial goal to achieve. The onset, maintenance, and progression of inflammatory bowel disease are related to abnormal intestinal immune responses to environmental factors, including diet and intestinal microflora components. This study aimed to evaluate the potential antiinflammatory and antifibrotic effect of a biologically debittered olive cream and its probiotic oral administration in an experimental model of dextran sodium sulfate (DSS)–induced chronic colitis.Methods: Chronic colitis was induced in mice by three cycles of oral administration of 2.5% DSS (5 d of DSS followed by 7 d of tap water). Mice were randomly divided into five groups: 10 control mice fed with standard diet (SD), 20 mice receiving SD and DSS (SD+DSS), 20 mice receiving an enriched diet (ED) with olive cream and DSS (ED+DSS), 20 mice receiving SD plus probiotics (PB; Lactiplantibacillus plantarum IMC513) and DSS (SD+PB+DSS), and 20 mice receiving ED plus PB and DSS (ED+ PB+DSS). Clinical features and large bowel macroscopic, histologic, and immunohistochemical findings were evaluated.Results: The simultaneous administration of ED and PB induced a significant reduction in macroscopic and microscopic colitis scores compared with the other DSS-treated groups. In addition, ED and PB led to a significant decrease in the expression of inflammatory cytokines and profibrotic molecules.Conclusions: The concomitant oral administration of a diet enriched with biologically debittered olive cream and a specific probiotic strain (Lactiplantibacillus plantarum IMC513) can exert synergistic antiinflammatory and antifibrotic action in DSS-induced chronic colitis. Further studies are needed to define the cellular and molecular mechanisms modulated by olive cream compounds and by Lactiplantibacillus plantarum IMC513.

Evaluation of Analytes Characterized with Potential Protective Action after Rat Exposure to Lead.

Lead (Pb) was revealed for its role as a neurodevelopmental toxin. The determination of neurotransmitters (NTs) in particular brain regions could ameliorate the precise description and optimization of therapeutic protocols able to restore the harmony of signaling pathways in nervous and immune systems. The determination of selected analytes from the group of NTs based on the liquid chromatography (LC)-based method was carried out to illustrate the changes of amino acid (AA) and biogenic amine (BA) profiles observed in chosen immune and nervous systems rat tissues after Pb intoxication. Also, a protective combination of AA was proposed to correct the changes caused by Pb intoxication. After the administration of Pb, changes were observed in all organs studied and were characterized by a fluctuation of NT concentrations in immune and nervous systems (hypothalamus samples). Using a protective mixture of bioactive compounds prevented numerous changes in the balance of NT. The combined analysis of the immune and nervous system while the normalizing effect of curative agents on the level of differentially secreted NTs and AA is studied could present a new approach to the harmonization of those two essential systems after Pb intoxication.

Probiotic Composition and Chondroitin Sulfate Regulate TLR-2/4-Mediated NF-κB Inflammatory Pathway and Cartilage Metabolism in Experimental Osteoarthritis.

The therapeutic potential of using probiotics to treat osteoarthritis (OA) has only recently been recognized, with a small number of animal and human studies having been undertaken. The aim of this study was to describe the effect of a probiotic composition (PB) and chondroitin sulfate (CS), administered separately or in combination, on Tlr2, Tlr4, Nfkb1, and Comp gene expression in cartilage and levels of cytokines (IL-6, IL-8, TGF-β1, IGF-1) and COMP, ACAN, CHI3L1, CTSK, and TLR-2 in serum during monoiodoacetate (MIA)-induced OA in rats. Expression of Tlr2, Tlr4, Nfkb1, and Comp in cartilage was analyzed using one-step SYBR Green real-time RT-PCR. The levels of IL-6, IL-8, TGF-β1, IGF-1, COMP, ACAN, CHI3L1, CTSK, and TLR-2 were measured in serum by enzyme-linked immunosorbent assay. Experimental OA caused an upregulation in Tlr2, Tlr4, Nfkb1, and downregulation of Comp expression in the cartilage. MIA-OA caused a significant increase of TLR-2 soluble form and IL-6, IL-8, TGF-β1, COMP, ACAN, CHI3L1, and CTSK levels in the blood serum; the level of IGF-1, on contrary, decreased. Separate administration of PB and CS raised expression of Comp and reduced Tlr2, Tlr4, and Nfkb1 expressions in cartilage. The levels of the studied markers of cartilage metabolism in serum were decreased or increased (IGF-1). The combined use of PB and CS was more effective than separate application approaching above-mentioned parameters to control. The outcomes of our research prove that multistrain live probiotic composition amplifies the positive action of CS in osteoarthritis attenuation and necessitates further investigation with large-scale randomized controlled trial.

Influence of Vitexin on ataxia-like condition initiated by lead exposure in mice

The study was aimed at investigating the influence of Vitexin on motor deficits and ataxia-like condition caused by Pb neurotoxicity in mice. Twenty four adult male albino mice were divided into four groups of six animals. Group A (Control) was administered 0.2 ml of normal saline; Group B was administered with Pb acetate 100 mg/kg/b.wt./d for 14 days; Group C was administered Vitexin 1 mg/kg/b.wt./d for 14 days; and Group D was administered 100 mg/kg/b.wt./d of Pb acetate + 1 mg/kg/b.wt./d of Vitexin for 14 days. Footprint pattern and Hang wire tests were carried out, while the level of malondialdehyde (MDA) and superoxide dismutase (SOD) in the cerebellum were assayed. Furthermore, cerebellum sections were stained with Haematoxylin and Eosin, while Purkinje cells were counted. Pb treated group showed that the MDA level was significantly high while the SOD level was low when compared with other groups. Also, loss of Purkinje cells, poor gait, and motor coordination were observed. In Pb + Vitexin treated group, the SOD level was significantly high while the MDA level was low. Besides, there was a significant improvement in gait, and motor coordination in Pb + Vitexin treated group. Pb neurotoxicity caused an increase in oxidative stress, loss of Purkinje cells, and ataxic-like symptoms. However, concurrent administration of Pb and Vitexin was able to neutralize oxidative stress and improve ataxic-like motor coordination.

Lead acetate- induced neurodegenerative changes in the dorsolateral prefrontal cortex of mice: the role of Vitexin.

This study was aimed at investigating the neuroprotective effect of Vitexin against lead (Pb) induced neurodegenerative changes in the dorsolateral prefrontal cortex (DLPFC) and working memory in mice. Thirty-two adolescent male albino mice were divided into four groups (n=8). Control group received 0.2 mL of normal saline; Pb group received 100 mg/kg of Pb acetate for 14 days, Vitexin group received 1mg/kg of Vitexin for 14 days, and Pb+Vitexin group received 100 mg/kg of Pb acetate and 1 mgkg of Vitexin for 14 days. Barnes maze test and novel object recognition test were done to ascertain working memory. Histoarchitectural assessment of DLPFC was done with haematoxylin and eosin (H&E), cresyl fast violet and congo red stains. Furthermore, cell count and other morphometric measurements were done. There was significant decline in working memory in the Pb group, but a combination of Pb+Vitexin improved the working memory. Vitexin significantly reduced neuronal death and chromatolysis caused by Pb. Amyloid aggregation was not observed in any of the groups. This study has shown that concurrent administration of Vitexin and Pb will significantly reduce neurodegeneration and improve working memory. However, Pb treatment or Pb+Vitexin treatment does not have any effect on intercellular distance, neuronal length and the cross-sectional area of neurons in layer III of DLPFC.

Pre- and Neonatal Exposure to Lead (Pb) Induces Neuroinflammation in the Forebrain Cortex, Hippocampus and Cerebellum of Rat Pups.

Lead (Pb) is a heavy metal with a proven neurotoxic effect. Exposure is particularly dangerous to the developing brain in the pre- and neonatal periods. One postulated mechanism of its neurotoxicity is induction of inflammation. This study analyzed the effect of exposure of rat pups to Pb during periods of brain development on the concentrations of selected cytokines and prostanoids in the forebrain cortex, hippocampus and cerebellum. Methods: Administration of 0.1% lead acetate (PbAc) in drinking water ad libitum, from the first day of gestation to postnatal day 21, resulted in blood Pb in rat pups reaching levels below the threshold considered safe for humans by the Centers for Disease Control and Prevention (10 µg/dL). Enzyme-linked immunosorbent assay (ELISA) method was used to determine the levels of interleukins IL-1β, IL-6, transforming growth factor-β (TGF-β), prostaglandin E2 (PGE2) and thromboxane B2 (TXB2). Western blot and quantitative real-time PCR were used to determine the expression levels of cyclooxygenases COX-1 and COX-2. Finally, Western blot was used to determine the level of nuclear factor kappa B (NF-κB). Results: In all studied brain structures (forebrain cortex, hippocampus and cerebellum), the administration of Pb caused a significant increase in all studied cytokines and prostanoids (IL-1β, IL-6, TGF-β, PGE2 and TXB2). The protein and mRNA expression of COX-1 and COX-2 increased in all studied brain structures, as did NF-κB expression. Conclusions: Chronic pre- and neonatal exposure to Pb induces neuroinflammation in the forebrain cortex, hippocampus and cerebellum of rat pups.

Effect of curcumin and curcumin nanoparticles against lead induced nephrotoxicity.

The aim of the present study was to examine the protective effect of curcumin (CUR) and curcumin nanoparticles (CURNPs) as antioxidants on the nephrotoxicity induced by lead (Pb). CUR (60 mg/kg b.w) and CURNPs (30 mg/kg b.w) were evaluated using Pb (30 mg/kg b.w.) induced oxidative renal damage in rats. Administration of Pb significantly (p<0.001) increased the levels of renal function test such as creatinine (CRN) and blood urea nitrogen (BUN) and uric acid (UA). Furthermore, Pb significantly decreased glutathione (GSH) levels, superoxide dismutase (SOD), glutathione reductase (GR), catalase (CAT) and glutathione peroxidase (GPx) activities (p<0.001). CUR and CURNPs displayed a renal protective effect as evident by significant decrease in CRN, BUN, UA levels and elevated the antioxidant status of renal tissues. The administration of Pb also induced histopathological changes in renal tissue; however, in groups treated by CUR and CURNPs, there was amelioration in pathological changes in renal tissue. These findings suggest that Nano CUR could be a potential compound in combating the oxidative damage of renal tissue as it increases curcumin bioavailability.

Semi-Rational Screening of Probiotics from the Fecal Flora of Healthy Adults against DSS-Induced Colitis Mice by Enhancing Anti-Inflammatory Activity and Modulating the Gut Microbiota.

Ulcerative colitis (UC), a chronic inflammatory bowel disease, substantially impacts patients' health-related quality of life. In this study, an effective strategy for discovering high-efficiency probiotics has been developed. First, in order to survive in the conditions of the stomach and intestine, high bile salt-resistant and strong acid-resistant strains were screened out from the fecal flora of healthy adults. Next, the probiotic candidates were rescreened by examining the induction ability of IL-10 (anti-inflammatory factor) production in dextran sodium sulfate (DSS)-induced colitis mice, and Lactobacillus sakei 07 (L07) was identified and selected as probiotic P. In the end, fourteen bifidobacterium strains isolated from stools of healthy males were examined for their antimicrobial activity. Bifidobacterium bifidum B10 (73.75% inhibition rate) was selected as probiotic B. Moreover, the colonic IL-6 and TNF-α expression of the DSSinduced colitis mice treated with L. sakei 07 (L07) - B. bifidum B10 combination (PB) significantly decreased and the IL-10 expression was up-regulated by PB compared to the DSS group. Furthermore, Bacteroidetes and Actinobacteria decreased and Firmicutes increased in the DSS group mice, significantly. More interestingly, the intestinal flora biodiversity of DSS colitis mice was increased by PB. Of those, the level of B. bifidum increased significantly. The Bacteriodetes/Firmicutes (B/F) ratio increased, and the concentration of homocysteine and LPS in plasma was down-regulated by PB in the DSS-induced colitis mice. Upon administration of PB, the intestinal permeability of the the DSS-induced colitis mice was decreased by approximately 2.01-fold. This method is expected to be used in high-throughput screening of the probiotics against colitis. In addition, the L. sakei 07 - B. bifidum B10 combination holds potential in UC remission by immunomodulatory and gut microbiota modulation.

Protective effect of garlic extract against maternal and foetal cerebellar damage induced by lead administration during pregnancy in rats

In spite of its industrial usefulness and varied daily uses, lead (Pb) pollution is a widespread ecological problem that faces the humans in the 21th century. Pb was found to produces a wide range of toxic effects including neurotoxicity especially to the developing and young offspring. Recently, the utilisation of herbal plants has received a significant attention where there has been rising awareness in their therapeutic use; among these is the garlic. In light of the above, the current study is designed experimentally in female pregnant rats in order to investigate the beneficial role of garlic extract in the protection from the maternal and foetal cerebellar damage produced by administration of different doses of Pb during pregnancy. Positively pregnant female rats were divided into five groups; one control group, two Pb-treated groups (exposed to 160 and 320 mg/kg b.w. of Pb, respectively) and two groups treated with both Pb and garlic (exposed to Pb as previous groups together with 250 mg/kg b.w./day of garlic extract). Treatments started from day 1 to day 20 of pregnancy, where the mother rats of different experimental groups were sacrificed to obtain the foetuses. Pb level in the maternal and foetal blood and cerebellum was estimated by spectrophotometry. Specimens of the cerebellum of different mother and foetal groups were processed to histological and immunohistochemical staining for microscopic examination. The results showed that administration of Pb to pregnant rats resulted in a dose-dependent toxicity for both mothers and foetuses in the form of decrease in maternal weight gain, placental and foetal weights, brain weight and diminished foetal growth parameters, which were prominent in rat's group treated with larger dose of Pb. In Pb-treated rats, Pb level in blood and cerebellum was high when compared with the control group. The histopathological examination of the cerebellum of treated dams and foetuses showed marked alterations mainly in the form of Purkinje cell degeneration and lack of development of foetal cerebellum. Co-treatment of garlic extract along with Pb resulted in a significant decrease in Pb levels as compared with those treated with Pb alone with improvement of the histopathological changes. This study was useful in evaluating the hazardous effects of uncontrolled use of Pb in general and in assessing the developmental and neurotoxicity of foetuses due to exposure during pregnancy in particular. Co-administration of garlic has beneficial effects in amelioration of Pb-induced neurotoxicity and reversing the histopathological changes of the cerebellum of mother rats and foetuses. (Folia Morphol 2018; 77, 1: 1-15).

STUDY OF INTERACTION BETWEEN LEAD AND GASTRIC MUCOSAL PROTEIN OF RATS WITH FORENSIC TOXICOLOGY APPROACH

Abstract: Recently, forensic toxicology has been an interesting concern, especially in exposing the phenomena associated with the law. Using the forensic toxicology approach, several cases of lead (Pb) poisoning have been widely revealed. In this present study will be investigate the interaction between Pb and amino acid gastric mucosal constituent proteins, especially cysteine and tyrosine groups. This research is a pure experimental research with posttest control group design, which is divided into 4 groups with 6 rats (Rattus novergicus) in each group. Treatment in each group as follows; P0 was control group were given 2 ml of distilled water; P1 = administration of Pb 0.1 g/L; P2 = Pb administration of 1 mg/L; and P3 = Pb administration of 10 g/L for 4 weeks repectively. According to the results, it can be concluded that Pb-Protein interaction tends to binding of Pb-Cysteine rather than Pb-Tyrosine Keywords: Gastric Mucosa, Lead, Protein

Aqueous extract of Polygonum bistorta modulates proteostasis by ROS-induced ER stress in human hepatoma cells

Hepatocellular carcinoma (HCC) remains the leading cause of cancer mortality with limited therapeutic targets. The endoplasmic reticulum (ER) plays a pivotal role in maintaining proteostasis in normal cells. However, alterations in proteostasis are often found in cancer cells, making it a potential target for therapy. Polygonum bistorta is used in traditional Chinese medicine owing to its anticancer activities, but the molecular and pharmacological mechanisms remain unclear. Using hepatoma cells as a model system, this study demonstrated that P. bistorta aqueous extract (PB) stimulated ER stress by increasing autophagosomes but by blocking degradation, followed by the accumulation of ubiquitinated proteins and cell apoptosis. In addition, an autophagy inhibitor did not enhance ubiquitinated protein accumulation whereas a reactive oxygen species (ROS) scavenger diminished both ubiquitinated protein accumulation and ligand-stimulated epidermal growth factor receptor (EGFR) expression, suggesting that ROS generation by PB may be upstream of PB-triggered cell death. Nevertheless, PB-exerted proteostasis impairment resulted in cytoskeletal changes, impairment of cell adhesion and motility, and inhibition of cell cycle progression. Oral administration of PB delayed tumour growth in a xenograft model without significant body weight loss. These findings indicate that PB may be a potential new alternative or complementary medicine for HCC.

Autonomic Responses to Orthostasis after Acetylcholinesterase Inhibition in Tetraplegia

PURPOSE: We have demonstrated that acetylcholinesterase inhibition (AcHi: pyridostigmine bromide: PB) improves orthostatic blood pressure (BP) responses to head-up tilt (HUT) compared to no drug (ND) in some individuals with tetraplegia and theorize that difference between subjects with an orthostatic BP response to PB (responders [R]) and those without a BP response (non-responders [nR]) may relate to the autonomic completeness of injury. Although we cannot directly asses the degree of autonomic cardiovascular impairment, we determined differences in the autonomic response to HUT using heart rate (HR) variability (HFV) and BP variability (BPV) after administration of PB (60 mg) compared to ND in subjects with tetraplegia. METHODS: Mixed factor ANOVA was used to determine main and interaction effects for high frequency HRV (HF: vagal) and low frequency BPV (LFsbp: sympathetic) responses to HUT (0°, 15°, 25°, 35°) following PB and ND administration in the R and nR. Beat-to-beat HR and BP were assessed using a 3-lead ECG and finger photoplethysmography, respectively; data were collected at 500 Hz for 5-minutes at each angle of HUT. RESULTS: Eleven individuals with SCI participated; however, one subject was unable to tolerate the HUT maneuver during ND therefore, results are presented in 10 subjects (age: 38±10 years; duration of injury: 13±10 years; level: C4-6; AIS: A, B, C). Five individuals were R and 5 were nR (+6.9±5.5 vs. -7.1±8.1 mmHg, respectively; p=0.012); demographics did not differ between the groups. Supine HR was lower in R compared to nR (48±3 vs. 57±8 bpm, respectively; p=0.049); supine BP did not differ. Although supine HF did not differ, supine LFsbp was increased in R compared to the nR (4.11±0.12 vs.3.82±0.24 ln, respectively; p=0.041). The group (R, nR) by condition (PB, ND) by HUT interaction effect was significant for HF (3.639; p=0.044), but not for LFsbp. CONCLUSION: These data suggest that tetraplegic individuals with increased resting sympathetic nervous system activity (LFsbp) respond to AcHi with an increased BP and vagal response to HUT, indicative of improved orthostatic baroreceptor function.

Apoptosis Sel-sel Spermatogenik Tikus Putih (Rattus norvegicus) Akibat Pajanan Plumbum (Pb)Serta Perbaikannya Setelah Pemberian Kitosan

Programmed cell death (apoptosis) of white rat spermatogenic cells can be caused by several factors, including heavy metals such as Cu, Au, Hg, Cd and Pb. The heavy metals found in industrial environments and some public places such as highways and oil pump. This study aims to reduce the negative effects of Pb by using chitosan obtained from shrimp shell processing of the garbage discarded in some shrimp producing areas. This study is divided into six treatment groups K1 = control; K2 = Pb; P1 = Pb+chitosan 0.5%; P2 = Pb = 0.75% chitosan, P3 = Pb+chitosan 1%, P4 = Pb+chitosan 1%. The results showed that administration of Pb causes apoptosis in spermatogenic cells (spermatogonia 78.26%; 84.7% spermatocytes, 77.1% spermatocytes). The addition of 1% chitosan is the best fix apoptotic spermatogenic cells after administration of Pb (Plumbum acetate). Keywords: apoptosis, cells spermatogenic, plumbum, chitosan.

Oxidative stress, biochemical alterations, and hyperlipidemia in female rats induced by lead chronic toxicity during puberty and post puberty periods.

Lead (Pb) is a toxic metal inducing many destructive effects leading to a broad range of physiological, biochemical, and neurological dysfunctions in humans and laboratory animals. Here, we investigated the effect of chronic exposure to Pb (50 mg/l) on oxidative stress, hepatotoxicity, nephrotoxicity, and lipid profile of two different age groups of female rats treated with Pb from delivery until puberty period (40 days, Pb40) and post puberty period (65 days, Pb65). Our results clearly show that the administration of Pb produces oxidative damage in liver and kidney, as strongly suggested by the significant increase in TBARS, decrease in total SH, and the alteration of SOD activity. Elevation in liver function biomarkers, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and reduction in total protein (liver and plasma) and albumin are evidence of perturbations of liver synthetic function. In young Pb-treated group, Pb-induced nephropathy was more pronounced by the increase in the levels of creatinine, urea, and uric acid. However, hyperlipidemia was evident for both Pb-exposed groups leading to a potential risk for cardiovascular diseases and atherosclerosis. It is concluded that Pb induces metabolic and oxidative disturbances depending on the age of the animals, which are not negligible.

The effects of dietary lead on growth, bioaccumulation and antioxidant capacity in sea cucumber, Apostichopus japonicus.

Three different diets amended with lead nitrate [Pb(NO3)2] (100, 500 and 1000mg Pb/kg dry weight) and a Pb-free control diet (1.03mg Pb/kg dry weight) were fed to sea cucumber (Apostichopus japonicus) for 30 days. The patterns of Pb accumulation over time were determined in various tissues (body wall, intestine and respiratory tree), as well as growth performance and antioxidant enzymes activities. Pb accumulation in body wall and intestine increased with time in all dietary Pb treatments. When fed the highest Pb diet, the body wall exhibited the greatest Pb burden (16.37mg Pb/kg tissue wet weight), while Pb content in the intestine (2.68mg Pb/kg tissue wet weight) and the respiratory tree (1.78mg Pb/kg tissue wet weight) were lower than Pb content in the body wall by day 30. The body weight gain (BWG), specific growth rate (SGR) and survival rate (SR) had not been affected by 30 days oral administration of Pb supplemented diet. However, the antioxidant enzymes activities [superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)] of test groups were lower than control group in body wall and malondialdehyde (MDA) concentration in the body wall was opposite after 30 days in sea cucumbers. In summary, this work reports toxic effects in sea cucumber, A. japonicus, after dietary exposure to Pb.

Using soil properties to predict in vivo bioavailability of lead in soils

Soil plays a significant role in controlling the potential bioavailability of contaminants in the environment. In this study, eleven soils were used to investigate the relationship between soil properties and relative bioavailability (RB) of lead (Pb). To minimise the effect of source of Pb on in vivo bioavailability, uncontaminated study soils were spiked with 1500mg Pb/kg soil and aged for 10–12months prior to investigating the relationships between soil properties and in vivo RB of Pb using swine model. The biological responses to oral administration of Pb in aqueous phase or as spiked soils were compared by applying a two-compartment pharmacokinetic model to blood Pb concentration. The study revealed that RB of Pb from aged soils ranged from 30±9% to 83±7%. The very different RB of Pb in these soils was attributed to variations in the soils’ physico-chemical properties. This was established using sorption studies showing: firstly, Freundlich partition coefficients that ranged from 21 to 234; and secondly, a strongly significant (R2=0.94, P<0.001) exponential relationship between RB and Freundlich partition coefficient (Kd). This simple exponential model can be used to predict relative bioavailability of Pb in contaminated soils. To the best of our knowledge, this is the first such model derived using sorption partition coefficient to predict the relative bioavailability of Pb.

Effect of chronic administration of phenobarbital, or bromide, on pharmacokinetics of levetiracetam in dogs with epilepsy.

BackgroundLevetiracetam (LEV) is a common add‐on antiepileptic drug (AED) in dogs with refractory seizures. Concurrent phenobarbital administration alters the disposition of LEV in healthy dogs.Hypothesis/ObjectivesTo evaluate the pharmacokinetics of LEV in dogs with epilepsy when administered concurrently with conventional AEDs.AnimalsEighteen client‐owned dogs on maintenance treatment with LEV and phenobarbital (PB group, n = 6), LEV and bromide (BR group, n = 6) or LEV, phenobarbital and bromide (PB–BR group, n = 6).MethodsProspective pharmacokinetic study. Blood samples were collected at 0, 1, 2, 4, and 6 hours after LEV administration. Plasma LEV concentrations were determined by high‐pressure liquid chromatography. To account for dose differences among dogs, LEV concentrations were normalized to the mean study dose (26.4 mg/kg). Pharmacokinetic analysis was performed on adjusted concentrations, using a noncompartmental method, and area‐under‐the‐curve (AUC) calculated to the last measured time point.ResultsCompared to the PB and PB–BR groups, the BR group had significantly higher peak concentration (C max) (73.4 ± 24.0 versus 37.5 ± 13.7 and 26.5 ± 8.96 μg/mL, respectively, P < .001) and AUC (329 ± 114 versus 140 ± 64.7 and 98.7 ± 42.2 h*μg/mL, respectively, P < .001), and significantly lower clearance (CL/F) (71.8 ± 22.1 versus 187 ± 81.9 and 269 ± 127 mL/h/kg, respectively, P = .028).Conclusions and Clinical ImportanceConcurrent administration of PB alone or in combination with bromide increases LEV clearance in epileptic dogs compared to concurrent administration of bromide alone. Dosage increases might be indicated when utilizing LEV as add‐on treatment with phenobarbital in dogs.

Effects of conventional anticonvulsant drugs on generalized tonic-clonic seizures in Noda epileptic rats

Noda epileptic rats (NERs) present with clinico-pathological manifestations reminiscent of human generalized tonic-clonic epilepsy. Thus, this strain of rat has been a model of primary, generalized, tonic-clonic epilepsy. However, the infrequency of seizures in these rats makes the assessment of antiepileptic drugs (AEDs) difficult. Therefore, traditional AEDs have only been tested in NERs against audiogenic seizures evoked by weekly acoustic priming from 3 to 22 weeks of age or by using the kindling procedure in adult animals. Adult NERs are susceptible to changes in their environment, such as bedding replacement or unpleasant sensory stimuli. In the present study, traditional AEDs-phenobarbital (PB) and sodium valproate (VPA)-were evaluated against seizures evoked by strong environmental stimuli in mature NERs that had not been previously primed. The number of animals presenting with seizures decreased in a dose-dependent manner following administration of either PB (dose range 1.0-5.0mg/kg) or VPA (50 and 100mg/kg). Consequently, the utility of NERs as a model of generalized tonic-clonic epilepsy was confirmed. This type of protocol can be used to further evaluate AEDs and test effects of chronic administration of AEDs.