ABSTRACT
The aim of this study was to determine the content of vitamin C in the liver of rats exposed to dimethoate or pyrantel embonate as well as co-intoxication with both agents. Investigations were carried out in two stages. At each stage, the rats were divided into three experimental groups (I-III) and a control (C) group. In the first stage, rats from group I were administered pyrantel embonate at a two-week interval at a dose of 1/2 LD50, while the animals from group II received dimethoate for 28 days at a dose of 1/25 LD50, and those from group III - both mentioned compounds in an identical manner as in groups I and II. In the second stage, the rats from group I received pyrantel embonate at a dose of 1/5 LD50 for 3 consecutive days, while the animals from group II received dimethoate at a dose of 1/10 LD50 for 5 consecutive days, and those from III received both compounds, but pyrantel was administered on day 3, 4 and 5 of dimethoate administration. The concentration of vitamin C after pyrantel embonate and dimethoate administration was influenced not only by doses of the compounds used but also by the manner of their application (single or co-administration). Dimethoate delivered at a dose of 1/25 LD50 evoked an increase in vitamin C concentration that was observed to continue up to the 14th day after the exposure, whereas when applied at a dose of 1/10 LD50 it increased the vitamin C level only at the 3rd hour. A considerable decrease in the vitamin C level was reported after pyrantel treatment at a dose of 1/5 LD50. In rats from groups where the compounds were co-administered, increased level of vitamin C was observed at both stages of the experiment only in the first period after intoxication, i.e. up to the 6th hour.
Subject(s)
Ascorbic Acid/pharmacokinetics , Dimethoate/pharmacology , Insecticides/pharmacology , Liver/metabolism , Pyrantel/pharmacology , Animals , Dimethoate/toxicity , Dose-Response Relationship, Drug , Drug Synergism , Insecticides/toxicity , Male , Pyrantel/toxicity , Random Allocation , Rats , Rats, Wistar , Vitamins/pharmacokineticsABSTRACT
Ultrastructural changes induced in vitro by thiabendazole, levamisole, pyrantel and ivermectin in the free living larval stages of two trichostrongyles (Heligmosomoides polygyrus and Haemonchus contortus) were analysed. The observed damage for each anthelmintic is related to the known mode of action and compared to the damage commonly described in adults. The advantage of using larvae to study the effects of anthelmintics on the fine structure of nematodes rather than adults is described. Thiabendazole induced alteration of the cellular organization especially epithelial cells of the digestive tract. Changes in mitochondria were also seen. Levamisole caused contraction of muscle fibres whereas no specific lesions were observed with pyrantel. Ivermectin caused an hypertrophy of muscular groups. The interest of such a technique in research on the modes of action of anthelmintics is emphasized.
Subject(s)
Antinematodal Agents/toxicity , Haemonchus/drug effects , Ivermectin/toxicity , Levamisole/toxicity , Pyrantel/toxicity , Thiabendazole/toxicity , Trichostrongyloidea/drug effects , Animals , Haemonchus/ultrastructure , Larva , Mice , Microscopy, Electron , Sheep , Trichostrongyloidea/ultrastructureABSTRACT
The potential of fumarate reductase as a therapeutic target against the human pathogen Helicobacter pylori was investigated by studying the cytotoxicity of morantel, oxantel, and thiabendazole, known to inhibit the enzyme in parasitic worms. Nuclear magnetic resonance spectroscopy was employed to investigate the effects of the inhibitors on the fumarate reductase activity of laboratory-adapted and wild-type bacterial strains. Production of succinate from fumarate in H. pylori cells was inhibited by morantel, oxantel, and thiabendazole. Cell growth and viability techniques were used to examine the bacteriostatic and bactericidal effects of the three anthelmintics. Each of the antiparasites arrested growth and produced cell death in liquid cultures, although the minimal inhibitory and bactericidal concentrations of these compounds are such that they would not be of therapeutic use. The strength of the effects as measured by minimal inhibitory and bactericidal concentrations was oxantel > thiabendazole > morantel. The findings suggested that fumarate reductase is an essential component of the metabolism of H. pylori and as such constitutes a possible target for therapeutic intervention in the treatment of the bacterium.
