Extracted tetrodotoxin from puffer fish Lagocephalus lagocephalus induced hepatotoxicity and nephrotoxicity to Wistar rats

This study aimed to investigate the toxicity of raw and boiled tissue extracts of Lagocephalus lagocephalus flesh or liver. Five groups of six male Wistar rats each were used. Four groups received a daily intraperitoneal injection of raw or boiled tissue extracts of L. lagocephalus flesh and liver at a dose of 1 ml/100 g (v/w). The fifth group served as a sham and received a daily intraperitoneal injection of saline solution (1 ml/100 g of 0.9% NaCl, v/w). During the experiment, there was a slight decrease in body weight in all treated groups. Our results revealed that the activities of various enzymes like transaminase, alkaline phosphatase (ALP), gamma glutamyl transpeptidase (γ-GT) and lactate dehydrogenase (LDH) decreased in serum and increased in liver and kidney tissues, producing hepatotoxicity and nephrotoxicity in the treated rats. These observations on the toxicity of this Tunisian puffer fish revealing toxicity especially in the flesh, the edible part of fish, clearly indicate the danger of using this fish as food.Key words: Hepatotoxicity, Lagocephalus lagocephalus, nephrotoxicity

Methidathion-induced hematological, biochemical and hepatohistological alterations in rat: Ameliorative effects of selenium and zinc

The aim of this study was to determine the effect of a sub-acute 4-week exposure to methidathion (MD) on the hematological system and hepatic integrity of rats. We also assessed whether co-administration of micronutrients such as selenium (Se) and zinc (Zn) prevented MD-induced hepatic damage. Rats were randomly divided into four groups of six each: the first group served as a control which received standard diet, the second group received both Se (0.5mg/kg of diet) and Zn (0.227 g/l drinking water), the third group received only MD (5 mg/kg b.w. by gavage using corn oil as a vehicle), and the fourth group received MD and combined selenium and zinc. After four weeks, exposure to MD induced a significant increase in plasmatic activities of AST, ALT, ALP, LDH, and liver malondialdehyde level. In contrast, reduced glutathione level (GSH), and the activities of catalase (CAT), superoxide dismutase (SOD), and the glutathione peroxidase (GPx) content of hepatic tissue decreased significantly. Moreover, treatment with Se and Zn in MD-treated rats maintained all the biochemical parameters cited above. In conclusion, the obtained results indicate the ability of Se and Zn to attenuate the MD-induced liver and erythrocytes oxidative damage.Key words: Biochemical studies, liver, methidathion, oxidative stress, rat, selenium, zinc

A novel chalcone derivative which acts as a microtubule depolymerising agent and an inhibitor of P-gp and BCRP in in-vitro and in-vivo glioblastoma models

<p>Abstract</p> <p>Background</p> <p>Over the past decades, in spite of intensive search, no significant increase in the survival of patients with glioblastoma has been obtained. The role of the blood-brain barrier (BBB) and especially the activity of efflux pumps belonging to the ATP Binding Cassette (ABC) family may, in part, explain this defect.</p> <p>Methods</p> <p>The <it>in-vitro </it>activities of JAI-51 on cell proliferation were assessed by various experimental approaches in four human and a murine glioblastoma cell lines. Using drug exclusion assays and flow-cytometry, potential inhibitory effects of JAI-51 on P-gp and BCRP were evaluated in sensitive or resistant cell lines. JAI-51 activity on <it>in-vitro </it>microtubule polymerization was assessed by tubulin polymerization assay and direct binding measurements by analytical ultracentrifugation. Finally, a model of C57BL/6 mice bearing subcutaneous GL26 glioblastoma xenografts was used to assess the activity of the title compound <it>in vivo</it>. An HPLC method was designed to detect JAI-51 in the brain and other target organs of the treated animals, as well as in the tumours.</p> <p>Results</p> <p>In the four human and the murine glioblastoma cell lines tested, 10 μM JAI-51 inhibited proliferation and blocked cells in the M phase of the cell cycle, via its activity as a microtubule depolymerising agent. This ligand binds to tubulin with an association constant of 2 × 10⁵M^-1, overlapping the colchicine binding site. JAI-51 also inhibited the activity of P-gp and BCRP, without being a substrate of these efflux pumps. These <it>in vitro </it>studies were reinforced by our <it>in vivo </it>investigations of C57BL/6 mice bearing GL26 glioblastoma xenografts, in which JAI-51 induced a delay in tumour onset and a tumour growth inhibition, following intraperitoneal administration of 96 mg/kg once a week. In accordance with these results, JAI-51 was detected by HPLC in the tumours of the treated animals. Moreover, JAI-51 was detected in the brain, showing that the molecule is also able to cross the BBB.</p> <p>Conclusion</p> <p>These <it>in vitro </it>and <it>in vivo </it>data suggest that JAI-51 could be a good candidate for a new treatment of tumours of the CNS. Further investigations are in progress to associate the title compound chemotherapy to radiotherapy in a rat model.</p

Breast cancer resistance protein (BCRP/ABCG2): New inhibitors and QSAR studies by a 3D linear solvation energy approach

A series of compounds derived from naturally occurring flavonoids and synthetic analogs have been evaluated on cell lines overexpressing the wild-type breast cancer resistance protein (BCRP/ABCG2) half-transporter. Human ABCG2-transfected cells were used for screening their inhibitory activity. Five new natural compounds obtained from Morus mesozygia Stapf and one synthetic chromone, comprising a flavonoidic scaffold, were also evaluated. Based on the results obtained with a total of 34 compounds, a 3D linear solvation energy QSAR was investigated by VolSurf descriptors of molecular-interaction fields (MIFs) related to hydrophobic-interaction forces, polarisability and hydrogen-bonding capacity. Accuracy of the constructed 3D-QSAR model was attested by a correlation coefficient r2 of 0.77. Shape parameters and hydrophobicity were revealed to be major physicochemical parameters responsible for the inhibition activity of flavonoid derivatives and synthetic analogs towards ABCG2, whereas hydrogen-bond donor capacity appeared highly unfavorable

Microwave assisted solvent free synthesis of 1,3-diphenylpropenones

<p>Abstract</p> <p>Background</p> <p>1,3-Diphenylpropenones (chalcones) are well known for their diverse array of bioactivities. Hydroxyl group substituted chalcones are the main precursor in the synthesis of flavonoids. Till date various methods have been developed for the synthesis of these very interesting molecules. Continuing our efforts for the development of simple, eco-friendly and cost-effective methodologies, we report here a solvent free condensation of aryl ketones and aldehydes using iodine impregnated alumina under microwave activation. This new protocol has been applied to a variety of substituted aryl carbonyls with excellent yield of substituted 1,3-diphenylpropenones.</p> <p>Results</p> <p>Differently substituted chalcones were synthesized using iodine impregnated neutral alumina as catalyst in 79-95% yield in less than 2 minutes time under microwave activation without using any solvent. The reaction was studied under different catalytic conditions and it was found that molecular iodine supported over neutral alumina gives the best yield. The otherwise difficult single step condensation of hydroxy substituted aryl carbonyls is an attractive feature of this protocol to obtain polyhydroxychalcones in excellent yields. In order to find out the general applicability of this new endeavor it was successfully applied for the synthesis of 15 different chalcones including highly bioactive prenylated hydroxychalcone xanthohumol.</p> <p>Conclusion</p> <p>A new, simple and solvent free method was developed for the synthesis of substituted chalcones in environmentally benign way. The mild reaction conditions, easy work-up, clean reaction profiles render this approach as an interesting alternative to the existing methods.</p

Chalcones derivatives acting as cell cycle blockers: Potential anticancer drugs

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