Susceptibility of Angiostrongylus cantonensis Larvae to Anthelmintic Drugs

Abstract

Human helminthiasis affects approximately one in five people in the world and disproportionally affects the poorest and most deprived communities. Human angiostrongyliasis, caused by nematode Angiostrongylus cantonensis, is a neglected emerging disease with escalating importance worldwide. Chemotherapy is the main control method for helminthiasis, but the therapeutic arsenal is limited. This study aimed to evaluate the antiparasitic and molecular properties of the major available anthelmintic drugs against A. cantonensis in vitro. The first-stage larvae (L1), isolated from feces of an A. cantonensis-infected rat, were exposed to a set of 12 anthelmintic drugs in vitro. The larvae were monitored, and the concentration- and time-dependent viability alterations were determined. From 12 anthelmintic drugs, six (ivermectin, salamectin, moxidectin, pyrantel pamoate, albendazole and levamisole) were identified to affect the viability of A. cantonensis. The macrocyclic lactones (ivermectin, salamectin, moxidectin) and the imidazothiazole levamisole, were the most effective drugs, with IC50 ranging from 2.2 to 2.9 µM and a rapid onset of action. Albendazole, the most widely used anthelmintic in humans, had a slower onset of action, but an IC50 of 11.3 µM was achieved within 24 h. Molecular properties studies suggest that a less lipophilic character and low molecular weight could be favorable for the biological activity of the non-macrocyclic molecules. Collectively, our study revealed that macrocyclic lactones, levamisole, pyrantel pamoate, and albendazole are important anthelmintic agents against A. cantonensis. The results of this in vitro study also suggest that A. cantonensis L1 may be a particularly sensitive and useful model for anthelmintic studies.

The Existing Drug Nifuroxazide as an Antischistosomal Agent: In Vitro , In Vivo , and In Silico Studies of Macromolecular Targets

“…Parasites incubated with drug-free DMSO (0.5%) served as a control. The egg output and viability of adult schistosomes were assessed via microscopic readout at 1, 24, 48, and 72 h ( 33 ) using a Motic AE2000 inverted microscope (Vancouver, Canada) equipped with a Motic ultrahigh definition (UHD) camera and with a 48-inch 4K-UHD monitor system (LG Electronics, Taubaté, SP, Brazil) ( 55 ). The death of adult schistosomes was defined as no movement observed for at least 1 to 2 min of examination, whereas parasites with any body movement were considered viable ( 28 ).…”

Evaluating the Antischistosomal Activity of Dehydrodieugenol B and Its Methyl Ether Isolated from Nectandra leucantha─A Preclinical Study against Schistosoma mansoni Infection

“…Worm survival was assessed based on mobility and form. Organisms with a rigid, stick-shaped appearance were considered dead, while nematodes exhibiting a sinusoidal, worm-like shape were considered alive . The experiments were repeated three times.…”

Neolignans isolated from Saururus cernuus L. (Saururaceae) exhibit efficacy against Schistosoma mansoni

“…Statistical analyses were performed using Graph Pad Prism software 8.0 (San Diego, CA, USA). Data are presented as the mean ± standard deviation (SD) of at least three independent experiments, EC 50 and, CC 50 values were calculated using sigmoid dose–response curves 74 . For S. mansoni egg production, significant differences were determined by one-way analysis of variance (ANOVA) and applying Tukey's test for multiple comparisons with a level of significance set at P < 0.05.…”