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

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

The Cambrian-Ordovician succession in the Ougarta Range (western Algeria, North Africa) and interference of the Late Ordovician glaciation on the development of Lower Paleozoic transgression on northern Gondwana.

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