A.F. Pétavy

Université Claude Bernard Lyon 1

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M.E. Sarciron

Université Claude Bernard Lyon 1

S. Walbaum

Clinique Claude-Bernard

S. Deblock

Laboratoire Paul Painlevé

M Mojon

Université Claude Bernard Lyon 1

S. Azzouz

Abdelmalek Essaâdi University

C. Gabrion

Centre National de la Recherche Scientifique

Florence Persat

Hospices Civils de Lyon

B. Gilot

Inserm

M Coulet

Nestlé (Switzerland)

Mimoun Maache

bioMérieux (France)

Cooperative Institutions

Université Claude Bernard Lyon 1

Centre National de la Recherche Scientifique

Inserm

École Nationale Vétérinaire de Toulouse

Laboratoire de Chimie

Pathophysiology, Diagnosis and Treatment of Bone Diseases

Universidad de Granada

École d'Ingénieurs en Chimie et Sciences du Numérique

Office National de la Chasse et de la Faune Sauvage

École Normale Supérieure - PSL

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ASPECTS OF THE CYTOLOGICAL ACTIVITY OF EDELFOSINE, MILTEFOSINE, AND

S. Azzouz Mimoun Maache Mário Santos M.E. Sarciron A.F. Pétavy

To discover the mode of action of alkyl-lysophospholipids in Leishmania donovani, we studied the effects of edel- fosine, miltefosine, and ilmofosine on intracellular pH, the parasite's cell cycle, and the induction of apoptosis. The effect of the alkyl-lysophospholipids was combined with that of inhibitors of some pumps and exchange regulators of intracellular pH (NaV H+; Cl/CO-3; and the Na+/K+ ATPase). The effect of the 3 alkyl-lysophospholipids on intracellular pH was indirect; the primary action occurred in the parasite's cell membrane. To determine intracellular pH, we used flow cytometry for the macrophages and axenic amastigotes and spectrofluorometry for the promastigote forms. Apoptosis and the cell cycle were studied by flow cytom- etry. Treatment of the extracellular promastigote form of L. donovani with the 3 alkyl-lysophospholipids induced death by apoptosis, whereas in the infected cell they caused necrosis rather than apoptosis. Miltefosine and ilmofosine at doses of 38 (xM caused G2/M cell cycle inhibition in L. donovani promastigotes. Visceral leishmaniasis is an illness produced by trypanoso- matid parasites belonging to the Leishmania donovani complex and affects some 500,000 people yearly, with another 350 mil- lion in the world at risk of infection (Herwaldt, 1999). The usual symptoms of the disease are fluctuating fever, weight loss, and a general feeling of illness, together with hepatospleno- megaly. If untreated, the disease is fatal in 91% of the cases (Mesa-Valle et al., 1996). Treatments used to date, i.e., antimonials and arsenicals, al- though efficacious, are difficult to administer due to their tox- icity, and the parasites have developed resistance against many of the drugs in use (Pearson and Sousa, 1985). This has prompt- ed research to develop new drugs with activity against leish- maniasis.

Miltefosine

Intracellular parasite

Mode of Action

Amastigote

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Citations (0)

Natural occurrence of Echinococcus multilocularis Leuckart, 1863, in the domestic cat: first report from a peri-urban area in France.

A.F. Pétavy Corinne Prost J. Gevrey B. Gilot S. Deblock

Echinococcus multilocularis

Peri

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Chemotherapeutic targets for antiparasitic therapy

Drugs of the Future (2006)

Philippe Lawton M.-E. Sarciron A.F. Pétavy

Despite the worldwide importance of parasitic diseases, antiparasitic chemotherapy is faced with spreading resistance and a lack of interest from pharmaceutical companies. In recent years, however, powerful new research techniques, such as high-throughput screening and advanced proteomics, have emerged and allowed the identification of new molecules and potential targets. In addition, some new antiparasitic drugs benefited from antiretroviral and anticancer research. Since parasites share many metabolic routes with their hosts, efficient drugs must reach them without being harmful to the patient, and in this respect, selectivity is a key parameter. In this review, we cover the most important chemotherapeutic targets thus far identified within the complex host-parasite relationships.

Antiparasitic

Antiparasitic agent

10.1358/dof.2006.031.09.1025669

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Citations (6)

In vivo cultivation of Echinococcus multilocularis protoscoleces in micropore chambers

International Journal for Parasitology (1991)

Samar Al Nahhas C. Gabrion S. Walbaum A.F. Pétavy

Echinococcus multilocularis

Histogenesis

Metacestode

10.1016/0020-7519(91)90046-a

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Citations (10)

A comparative study of the fixation of lectins on the membrane of four species of Crithidia.

Protist (1980)

J Gueugnot A.F. Pétavy Jacques Guillot Mireille Damez M Coulet

Crithidia

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Citations (4)

Integrated health messaging for multiple neglected zoonoses: Approaches, challenges and opportunities in Morocco

Acta Tropica (2015)

Marie J. Ducrotoy Hind Yahyaoui Azami Ikhlass El Berbri Mohammed Bouslikhane Ouafaa Fassi Fihri

One Health

Behavior change communication

Zoonotic disease

10.1016/j.actatropica.2015.08.011

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Citations (18)

ChemInform Abstract: Phenylureas Derived from Indazole: Research on Anthelminthic Activity and the Effect of Substituents.

Chemischer Informationsdienst (1986)

O. BARBET M. MINJAT A.F. Pétavy J. M. PARIS

Abstract Since the compound (Ia) shows a certain activity against Syphacia obvelata, the analogues (Ib)‐(V) are synthesized according to known literature procedures (yields: 52‐97%).

Indazole

10.1002/chin.198652161

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EFFECT OF ALKYL-LYSOPHOSPHOLIPIDS ON SOME ASPECTS OF THE METABOLISM OF LEISHMANIA DONOVANI

Journal of Parasitology (2007)

S. Azzouz Mimoun Maache Manuel Sánchez‐Moreno A.F. Pétavy Antonio Osuna

Alkyl-lysophospholipids (ALPs), developed initially to be antitumor agents, have proved highly effective in the treatment of visceral leishmaniasis, a disease caused by the species making up the protozoan complex Leishmania donovani. Although their effectiveness is known, the mode of action against this parasite is not completely understood. In the present work, we have studied the effect of 3 derivatives, edelfosine, miltefosine, and ilmofosine. Using nuclear magnetic resonance spectroscopy (1H-NMR), we have examined the excreted catabolites from glucose metabolism in the promastigote forms treated with these compounds. The ALPs at concentrations of 19 and 38 μM inhibit the excretion of acetate, succinate, and pyruvate. The effect of edelfosine, miltefosine, and ilmofosine on the activity of the enzymes hexokinase, glycerolkinase 3-PD, phosphoglucose isomerase, superoxide dismutase, and phospholipase C were also examined. Glycerolkinase 3-PD and phosphoglucose isomerase are generally insensitive to the compounds, whereas hexokinase and superoxide dismutase are inhibited by miltefosine and ilmofosine. The ALPs exhibited an activated effect against the phospholipase C activity. Alkyl-lysophospholipids were shown to have a significant effect on several enzymes in important biochemical pathways indispensable for the survival of L. donovani promasigotes.

Miltefosine

Glucose-6-phosphate isomerase

10.1645/ge-1086r1.1

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Effects of artesunate, dihydroartemisinin, and an artesunate-dihydroartemisinin combination against Toxoplasma gondii.

American Journal of Tropical Medicine and Hygiene (2000)

M.E. Sarciron C Saccharin A.F. Pétavy François Peyron

The effect of artesunate and its metabolite dihydroartemisinin against the cerebral cysts of Toxoplasma gondii was studied. In vitro experiments were performed with the THP-1 cell line and showed an inhibition of parasite growth of approximately 70% with 0.1-0.5 microg/ml of dihydroartemisinin for 96 hr. However, with artesunate, dihydroartemisinin, or a combination (50:50) of them, the number of tachyzoites decreased approximately 40-50% and they appeared motionless. Fifty-eight to 72 hr after washing of the tachyzoites and THP-1 cells in culture, parasitized cells reappeared. In vivo, the 50:50 artesunate-dihydroartemisinin combination produced a decrease in cerebral cysts of approximately 40% after only 5 days of treatment. However, transplantations into naive mice using brains of treated mice gave positive results.

Dihydroartemisinin

Artesunate

10.4269/ajtmh.2000.62.73

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Citations (44)

Épidémiologie de l’échinococcose alvéolaire en France I. — Helminthes intestinaux du renard commun (Vulpes vulpesL.) en Haute-Savoie

Annales de Parasitologie Humaine et Comparée (1990)

A.F. Pétavy S. Deblock Corinne Prost

Au cours d’une enquête épidémiologique concernant l’échinococcose alvéolaire en Haute-Savoie (France) et son agent pathogène Echinococcus multilocularis, l’autopsie de 150 renards sauvages capturés de décembre 1983 à août 1988 a mis en évidence 139 cas d’helminthiase intestinale à cestode ou à nématode. Aucun trématode n’a été récolté. Le polyparasitisme est la règle générale. Les cestodoses concernent Taenia crassiceps : 44 cas (29 %) ; Echinococcus multilocularis : 34 cas (23 %) ; Taenia polyacantha : 22 cas (14 %) ; Mesocestoides litteratus : 7 cas (4,6 %) ; Amoebotaenia paradoxa : 1 cas (0,6 %). Les nématodoses concernent : Uncinaria stenocephala : 79 cas (52 %) ; Toxocara canis : 67 cas (44 %); Toxascaris leonina : 16 cas (10 %); Trichuris vulpis : 12 cas (8 %) ; Pterigodermatites affinis : 8 cas (5 %); Trichostrongyloïdes sp. : 5 cas (3 %). La trichinose n’a pas été recherchée. Ces résultats sont comparés à ceux de même nature observés précédemment en Auvergne.

10.1051/parasite/1990651022

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Citations (23)