Postnatal exposure to Bisphenol S induces liver injury in mice: Possible implication of PPARγ receptor.

There is considerable evidence that Bisphenol S (BPS) induces various toxicological effects and is an industrial health issue. However, little data are available on the in vivo effects of BPS on the liver, a major target of drug toxicity. In this study, we evaluated the potential harmfulness of low levels of BPS in the liver of male mice. Also, we investigated the interaction between BPS and peroxisome proliferator-activated receptor-gamma (PPARγ) by computational docking approach. PPARγ is a member of the superfamily of nuclear hormone receptors. It acts as a transcription factor and regulates the genes involved in lipid and glucose metabolism and in inflammation and necrosis. Mice were exposed to BPS, in drinking water at 25, 50, and 100 µg/kg for 10 weeks. The protocol was started after weaning. At the time of sacrifice, blood samples were collected for a biochemical analysis, followed by liver tissue collection for histopathological study. Results showed that BPS-induced hypertriglyceridemia, increased liver injury markers, and initiated histopathological changes, including inflammatory cell infiltration, hepatocellular necrosis, and steatosis. BPS did not affect glycated hemoglobin (HbA1C). Interestingly, data showed that BPS could interact with the PPARγ ligand-binding pocket by hydrogen bonds with Asn 219, Cys 276, Ser 280, and Thr 283. We suggest that PPARγ is among the targets of BPS and could play a key role in the cascade reaction of BPS-induced liver disruption. These findings support the hypothesis that the post-weaning period is sensitive to low-dose BPS exposure that can lead to dyslipidemia signature later in life.

Inhibition of avian influenza virus H9N2 infection by antiviral hexapeptides that target viral attachment to epithelial cells.

The H9N2 subtype of influenza A virus circulates frequently among poultry in Asian and North African countries causing economic loss in the poultry sector. The antigenic variations of the H9N2 virus were at the origin of its genetic evolution through the emergence of viral strains transmissible to humans and resistant to chemical antivirals, which require a strengthening of the fight means against this virus. In this study, we used a random linear hexapeptide library fused to the gene III protein of M13 filamentous bacteriophage to select new antiviral peptides that inhibit the infectivity of H9N2 virus. After three rounds of stringent selection and amplification, polyclonal phage-peptides directed against H9N2 virus were assessed by ELISA, and the optimal phage-peptides were grown individually and characterized for binding to H9N2 virus by monoclonal phage ELISA. The DNA of 27 phage-peptides clones was amplified by PCR, sequenced, and their amino acid sequences were deduced. Sixteen different phage-peptides were able to bind specifically the H9N2 virus, among them, 13 phage-peptides interacted with the hemagglutinin H9. Two selected peptides, P1 (LSRMPK) and P2 (FAPRWR) have shown antiviral activity in ovo and P1 was more protective in vivo then P2 when co-administered with the H9N2 virus. Mechanistically, these peptides prevent infection by inhibiting the attachment of the H9N2 virus to the cellular receptor. Molecular docking revealed that the peptides LSRMPK and FAPRWR bind to hemagglutinin protein H9, but interact differently with the receptor binding site (RBS). The present study demonstrated that the peptide P1 (LSRMPK) could be used as a new inhibitory molecule directed against the H9N2 virus.

Ketamine, at low dose, decrease behavioural alterations in epileptic diseases induced by pilocarpine in mice.

Objective: The objective of the present study was to evaluate the effect of low-dose of ketamine, in short-term, on behavioral impairment and acute neuronal death in the cerebral cortex during the acute phase in a model of epileptic mouse induced by pilocarpine.Methods:Ketamine was administrated (10 mg/kg) intraperitoneally, 30 min before pilocarpine injection (100 mg/kg) in the first group. The second group received the same dose of ketamine 30 min after pilocarpine injection. The effect of ketamine on behavioral disorders and cerebral neuronal integrity in epileptic mice was evaluated.Results:Clinical observations and behavioural tests relate a reduction in behavioural dysfunctions in mice treated with ketamine. Interestingly, treatment of mice with low dose of ketamine decreased the clinical symptoms (movements of the vibrios, nods of the head, and movements of the whiskers), especially when administered before epilepsy induction. Furthermore, the administration of ketamine limits oedema in the hippocampus, neuronal degeneration and gliosis in the different cortical layers. These results could be explained by NMDA receptors inhibition by ketamine.Conclusion:Therefore, it appears that ketamine is endowed with a potential neuroprotective effect and can reduce the severity of neurodegeneration, especially when administrated before Status Epilepticus (SE) installation.

Individual and synergistic protective properties of Salvia officinalis decoction extract and sulfasalazine against ethanol-induced gastric and small bowel injuries.

The present study was carried out to determine the phytochemical composition of Salvia officinalis flowers decoction extract (SOFDE) as well as its individual and/or synergistic actions with sulfasalazine against ethanol (EtOH)-induced peptic ulcer in Wistar rats. In this respect, rats were divided into six groups of eight animals each: control, EtOH, EtOH + sulfasalazine (SULF, 100 mg kg-1, b.w., p.o.), mixture: MIX (SOFDE, 50 mg kg-1 b.w., p.o. + SULF, 50 mg kg-1, b.w., p.o.) and EtOH + two doses of SOFDE (100 and 200 mg kg-1 b.w., p.o.). In vitro, the phytochemical and the antioxidant properties were determined using colorimetric analysis. HPLC-PDA/ESI-MS assay was used to identify the distinctive qualitative profile of phenolic compounds. Our results firstly indicated that SOFDE is rich in total tannins, flavonols, anthocyanins and a moderate concentration of total carotenoids. Chromatographic techniques allowed the identification of 13 phenolic compounds and the major ones are quinic acid, protocatechuic acid, gallic acid and salviolinic acid. SOFDE also exhibited an important in vitro antioxidant activity using the ß-carotene bleaching method. In vivo, SOFDE and the mixture provide significant protection against ethanol-induced gastric and duodenal macroscopic and histological alterations. Also, SOFDE alone or in combination with SULF, showed a significant protection against the secretory profile disturbances, lipid peroxidation, antioxidant enzyme activities and non-enzymatic antioxidant level depletion induced by alcohol administration. Importantly, we showed that EtOH acute intoxication increased gastric and intestinal calcium, free iron, magnesium and hydrogen peroxide (H2O2) levels, while SOFDE/MIX treatment protected against all these intracellular mediators' deregulation. We also showed that alcohol treatment significantly increased the C-reactive protein (CRP) and alkaline phosphatase (ALP) activities in plasma. The SOFDE and MIX treatment significantly protected against alcohol-induced inflammation. More importantly, we showed in the present work that the mixture exerted a more important effect than SOFDE and SULF each alone indicating a possible synergism between these two molecules. In conclusion, our data suggests that SOFDE and SULF exerted a potential synergistic protective effect against all the macroscopic, histological and biochemical disturbances induced by EtOH intoxication. This protection might be related in part to its antioxidant and anti-inflammatory properties as well as by negatively regulating Fenton reaction components such as H2O2 and free iron.

Dittrichia viscosa L. Ethanolic Extract Based Ointment with Antiradical, Antioxidant, and Healing Wound Activities.

Dittrichia viscosa which belongs to the Asteraceae family is frequently used to treat hematomas and skin disorders in Mediterranean herbal medicine. This study aims to validate its antioxidant effects and its potential on healing wounds. The ethanolic extract of D. viscosa leaves was formulated as 2.5% and 5% (w/w) in ointment bases on the beeswax and sesame oil. During this study, the ethanolic D. viscosa extract, ointments containing 2.5% and 5% of D. viscosa extract, and the vehiculum were assessed for their total phenol content (TPC), caffeoylquinic acid content (CQC), and antioxidant activities using complementary methods (TAC, the DPPH, ABTS, FRAP, and the BCB). The effects on wound healing of obtained ointments were evaluated by excision of the wound in a mice model for 12 days. Subsequently, the excised wound areas were measured at the 3rd, 9th, and 12th days. The skin tissues were isolated for histological studies. The ointments containing D. viscosa extract (2.5%, 5%) possessed a considerable TPC, CQC, radical scavenging potential, and antioxidant activities compared to the vehiculum. Treated animals with ointments containing D. viscosa extract at 2.5% and 5% showed almost and totally healed wounds compared to the vehiculum and control groups, evidenced by good skin regeneration and reepithelialization. The present work showed the role of D. viscosa antioxidants exerted by its polyphenolic compounds, in particular, caffeoylquinic acids, in enhancing wound healing.

FecX Bar a Novel BMP15 mutation responsible for prolificacy and female sterility in Tunisian Barbarine Sheep.

BACKGROUND: Naturally occurring mutations in growth and differentiation factor 9 (GDF9) or bone morphogenetic protein 15 (BMP15) genes are associated with increased ovulation rate (OR) and litter size (LS) but also sterility. Observing the Tunisian Barbarine ewes of the "W" flock selected for improved prolificacy, we found prolific and infertile ewes with streaky ovaries. Blood genomic DNA was extracted from a subset of low-ovulating, prolific and infertile ewes of the "W" flock, and the entire coding sequences of GDF9 and BMP15 were sequenced. RESULTS: We evidenced a novel polymorphism in the exon 1 of the BMP15 gene associated with increased prolificacy and sterility. This novel mutation called FecX Bar is a composite polymorphism associating a single nucleotide substitution (c.301G > T), a 3 bp deletion (c.302_304delCTA) and a C insertion (c.310insC) in the ovine BMP15 cDNA leading to a frame shift at protein position 101. Calculated in the "W" flock, the FecX Bar allele increased OR by 0.7 ova and LS by 0.3 lambs (p = 0.08). As for already identified mutations, homozygous females carrying FecX Bar exhibited streaky ovaries with a blockade at the primary stage of folliculogenesis as shown by histochemistry. CONCLUSIONS: Our investigation demonstrates a new mutation in the BMP15 gene providing a valuable genetic tool to control fecundity in Tunisian Barbarine, usable for diffusion program into conventional flocks looking for prolificacy improvement.

Evaluation of oxidative response and tissular damage in rat lungs exposed to silica-coated gold nanoparticles under static magnetic fields.

The purpose of our study was the evaluation of toxicological effects of silica-coated gold nanoparticles (GNPs) and static magnetic fields (SMFs; 128 mT) exposure in rat lungs. Animals received a single injection of GNPs (1,100 µg/kg, 100 nm, intraperitoneally) and were exposed to SMFs, over 14 days (1 h/day). Results showed that GNPs treatment induced a hyperplasia of bronchus-associated lymphoid tissue. Fluorescence microscopy images showed that red fluorescence signal was detected in rat lungs after 2 weeks from the single injection of GNPs. Oxidative response study showed that GNPs exposure increased malondialdehyde level and decreased CuZn-superoxide dismutase, catalase, and glutathione peroxidase activities in rat lungs. Furthermore, the histopathological study showed that combined effects of GNPs and SMFs led to more tissular damages in rat lungs in comparison with GNPs-treated rats. Interestingly, intensity of red fluorescence signal was enhanced after exposure to SMFs indicating a higher accumulation of GNPs in rat lungs under magnetic environment. Moreover, rats coexposed to GNPs and SMFs showed an increased malondialdehyde level, a fall of CuZn-superoxide dismutase, catalase, and glutathione peroxidase activities in comparison with GNPs-treated group. Hence, SMFs exposure increased the accumulation of GNPs in rat lungs and led to more toxic effects of these nanocomplexes.

First report of surra (Trypanosoma evansi infection) in a Tunisian dog.

Trypanosoma evansi, the agent of surra, is a salivarian trypanosome, originating from Africa. Surra is a major disease in camels, equines and dogs, in which it can often be fatal in the absence of treatment. Animals exhibit nonspecific clinical signs (anaemia, loss of weight and abortion). In the present survey, a blood sample was collected in Sousse (Central Tunisia) from a dog that presented clinical signs of trypanosomiasis. Giemsa-stained blood smears and PCR were performed. ITS1 sequences from blood had 99.8 and 99.5% homology with published T. evansi sequences from cattle and camels, respectively. To our knowledge, this is the first report of T. evansi in a Tunisian dog.

Preliminary safety assessment of Yarrowia lipolytica extracellular lipase: results of acute and 28-day repeated dose oral toxicity studies in rats.

Interest in extracellular lipase sourced from the non conventional yeast Yarrowia lipolytica has increased over the last decade. The enzyme was recently suggested as a good candidate for pancreatic exocrine insufficiency treatment. However, there is still a lack of oral safety evaluation data. In this work, we conducted acute and 28-day repeated dose toxicity studies in rats. Both male and female rats were first orally treated with fungal lipase at either single or repeated doses. The results demonstrated that neither single dose nor chronic administration of lipase was associated with mortality or abnormalities in general conditions, behavior and growth. Except a decrease in urine pH and a dose-unrelated increase of triglycerides observed in males, chronic administration of lipase resulted in similar hematological, blood biochemical and urine parameters to those of untreated animals. Minor histopathological changes were observed in lungs and livers of treated and untreated animals but they were considered of no toxicological significance. This study provides, for the first time, safety data on Yarrowia lipolytica extracellular lipase that support its use as a pharmaceutical.