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Dimier-Poisson, I.

Publications and source records attributed to Dimier-Poisson, I..

2 recordsLinked to original sources

Extracts of food and medicinal plants sold in Moroccan markets induce apoptosis-like in Toxoplasma gondii tachyzoites in vitro

Treatment of congenital toxoplasmosis is potentially toxic and above all too expensive to be administered systematically in middle-income countries such as Morocco. There is therefore a real interest in discovering alternative treatments that would be financially accessible to all. In this context, plants used in traditional medicine and purchased in markets are good candidates. Aqueous extract of Ammi visnaga seeds had no inhibitory effect against T. gondii tachyzoites intracellular growth in vitro and induced a cytotoxic effect on host cells. In contrast, ethanolic extract of A. visnaga seeds showed anti-Toxoplasma effect with low cytotoxicity, indicating the compounds extracted differed according to the solvent used. Aqueous extracts of Punica granatum peel and Syzygium aromaticum flower buds also showed anti-Toxoplasma effect with low cytotoxicity. All the extracts tested, with a greater effect from aqueous and ethanolic extracts of A. visnaga seeds, induced apoptosis-like of extracellular tachyzoites, as determined by exposure of phosphatidylserine on tachyzoite surface and DNA fragmentation. Finally, the aqueous extracts of A. visnaga seeds, P. granatum peel and S. aromaticum flower buds exhibited antioxidant properties. Phytochemical analysis indicated that coumarins and sterols from the aqueous extract of A. visnaga, saponins from the ethanolic extract of A. visnaga, gallic tannins from the extract of P. granatum, and phenols from the extract of S. aromaticum were certainly the main components responsible for the different effects observed. The results suggested that the seeds of A. visnaga and the peel of P. granatum are the two best candidates for possible preclinical studies on toxoplasmosis.

microbiology↗

Distinct molecular targets for macrocyclic lactone and isoxazoline insecticides in the human louse: new prospects for the treatment of pediculosis

BackgroundControl of infestation by cosmopolitan lice (Pediculus humanus) is increasingly difficult due to the transmission of resistant parasites to pediculicides. However, since the targets for pediculicides have no been identified in human lice so far, their mechanism of action remain largely unknown. The macrocyclic lactone, ivermectin is active against a broad range of insects including human lice. Isoxazolines are a recent new chemical class targeting the {gamma}-aminobutyric acid (GABA) receptor made of the resistant to dieldrin (RDL) subunit and exhibiting a strong insecticidal potential. Here, we addressed the pediculicidal potential of isoxazolines and deciphered the molecular targets of ivermectin and the novel ectoparasiticide lotilaner in the human body louse species Pediculus humanus humanus. Methods and findingsUsing toxicity bioassays, we showed that fipronil, ivermectin and lotilaner are efficient pediculicides on adult lice. The RDL (Phh-RDL) and glutamate-gated chloride channel subunits (Phh-GluCl) were cloned and characterized by two-electrode voltage clamp electrophysiology in Xenopus laevis oocytes. Phh-RDL and Phh-GluCl formed functional homomeric receptors respectively gated by GABA and L-glutamate with EC50 values of 6.4 {micro}M and 9.3 {micro}M. Importantly, ivermectin displayed a super agonist action on Phh-Glucl whereas Phh-RDL receptors were weakly affected. Reversally, lotilaner strongly inhibited the GABA-evoked currents in Phh-RDL with an IC50 value 0.5 {micro}M, whereas it had no effect on Phh-GluCl. ConclusionsWe report here for the first time the pediculicidal potential of isoxazolines and reveal the distinct mode of action of ivermectin and lotilaner on GluCl and RDL channels from human lice. These results emphasize the clear repurposing future of the isoxazoline drug class to provide new pediculicidal agents to tackle resistant-louse infestations in humans. Autorship summaryO_ST_ABSWhy was this study done?C_ST_ABSHuman cosmopolitan lice are responsible for pediculosis, which represent a significant public health concern. Resistant lice against insecticides and lack of safety of the treatments for human and environment is a growing issue worldwide. Here we investigated the efficacy on lice of the classical macrocyclic lactone drug, ivermectin, and the novel isoxazoline drug, lotilaner. This study was done to decipher their mode of action at the molecular and funtional levels in order to propose new strategies to control lice infestation. What did the researchers do and find?Our bioassay results indicate that ivermectin and lotilaner were potent at killing human adult lice, with lotilaner showing a higher efficacy than ivermectin. Furthermore, we identified and pharmacologically characterized the first glutamate- and GABA-gated chloride channels ever described in human lice yet. Mechanistically, our molecular biology and electrophysiology findings demonstrate that ivermectin acted preferentially at glutamate channels while lotilaner specifically targeted GABA channels. What do these findings mean?These results provide new insights in the understanding of the insecticide mode of action and highlight the isoxazolines as a new drug-repurposing opportunity for pest control strategies.

pharmacology and toxicology↗