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British Journal of Pharmacology Dec 2023Nitazoxanide is a therapeutic anthelmintic drug. Our previous studies found that nitazoxanide and its metabolite tizoxanide activated adenosine...
BACKGROUND AND PURPOSE
Nitazoxanide is a therapeutic anthelmintic drug. Our previous studies found that nitazoxanide and its metabolite tizoxanide activated adenosine 5'-monophosphate-activated protein kinase (AMPK) and inhibited signal transducer and activator of transcription 3 (STAT3) signals. As AMPK activation and/or STAT3 inhibition are targets for treating pulmonary fibrosis, we hypothesized that nitazoxanide would be effective in experimental pulmonary fibrosis.
EXPERIMENTAL APPROACH
The mitochondrial oxygen consumption rate of cells was measured by using the high-resolution respirometry system Oxygraph-2K. The mitochondrial membrane potential of cells was evaluated by tetramethyl rhodamine methyl ester (TMRM) staining. The target protein levels were measured by using western blotting. The mice pulmonary fibrosis model was established through intratracheal instillation of bleomycin. The examination of the lung tissues changes were carried out using haematoxylin and eosin (H&E), and Masson staining.
KEY RESULTS
Nitazoxanide and tizoxanide activated AMPK and inhibited STAT3 signalling in human lung fibroblast cells (MRC-5 cells). Nitazoxanide and tizoxanide inhibited transforming growth factor-β1 (TGF-β1)-induced proliferation and migration of MRC-5 cells, collagen-I and α-smooth muscle cell actin (α-SMA) expression, and collagen-I secretion from MRC-5 cells. Nitazoxanide and tizoxanide inhibited epithelial-mesenchymal transition (EMT) and inhibited TGF-β1-induced Smad2/3 activation in mouse lung epithelial cells (MLE-12 cells). Oral administration of nitazoxanide reduced the bleomycin-induced mice pulmonary fibrosis and, in the established bleomycin-induced mice, pulmonary fibrosis. Delayed nitazoxanide treatment attenuated the fibrosis progression.
CONCLUSIONS AND IMPLICATIONS
Nitazoxanide improves the bleomycin-induced pulmonary fibrosis in mice, suggesting a potential application of nitazoxanide for pulmonary fibrosis treatment in the clinic.
Topics: Humans; Mice; Animals; Pulmonary Fibrosis; Transforming Growth Factor beta1; AMP-Activated Protein Kinases; Bleomycin; Collagen Type I; Disease Models, Animal; Anthelmintics; Mice, Inbred C57BL; Nitro Compounds; Thiazoles
PubMed: 37428102
DOI: 10.1111/bph.16190 -
Natural Product Reports Nov 2023Covering literature to December 2022This review provides a comprehensive account of all natural products (500 compounds, including 17 semi-synthetic derivatives)... (Review)
Review
Covering literature to December 2022This review provides a comprehensive account of all natural products (500 compounds, including 17 semi-synthetic derivatives) described in the primary literature up to December 2022, reported to be capable of inhibiting the egg hatching, motility, larval development and/or the survival of helminths (, nematodes, flukes and tapeworms). These parasitic worms infect and compromise the health and welfare, productivity and lives of commercial livestock (, sheep, cattle, horses, pigs, poultry and fish), companion animals (, dogs and cats) and other high value, endangered and/or exotic animals. Attention is given to chemical structures, as well as source organisms and anthelmintic properties, including the nature of bioassay target species, animal hosts, and measures of potency.
Topics: Animals; Cattle; Sheep; Horses; Dogs; Cats; Swine; Biological Products; Cat Diseases; Dog Diseases; Anthelmintics; Nematoda; Helminths
PubMed: 37555325
DOI: 10.1039/d3np00019b -
The New England Journal of Medicine May 2024
Topics: Animals; Humans; Male; Elephantiasis, Filarial; Filaricides; Wuchereria bancrofti; Aged; Treatment Outcome; Doxycycline; Albendazole; Diethylcarbamazine; Edema; Penis; Scrotum; Leg; Magnetic Resonance Imaging
PubMed: 38708851
DOI: 10.1056/NEJMicm2313316 -
Parasitology International Jun 2024Follicular larva migrans (FLM) is a rare and atypical clinical presentation of hookworm-related cutaneous larva migrans (HrCLM). FLM is characterized clinically by... (Review)
Review
Follicular larva migrans (FLM) is a rare and atypical clinical presentation of hookworm-related cutaneous larva migrans (HrCLM). FLM is characterized clinically by follicular, round, small, erythematous papules that are sometimes topped by vesicles or pustules. These lesions are usually located on the abdomen, back, buttocks and thighs and are accompanied by more or less severe pruritus. Some typical and/or short and fragmented tracks may also be visible. FLM is more resistant to anti-helminthic drugs than classical HrCLM: this is likely due to the deep location of larvae in hair follicles. We present two cases of FLM and a review of the literature.
Topics: Animals; Larva Migrans; Anthelmintics; Ancylostomatoidea; Larva
PubMed: 38428565
DOI: 10.1016/j.parint.2024.102872 -
International Journal For Parasitology Jul 2023
Topics: Anthelmintics; Vaccines; Drug Resistance
PubMed: 37257805
DOI: 10.1016/j.ijpara.2023.05.004 -
Ugeskrift For Laeger May 2024
Topics: Humans; Male; Testicular Diseases; Schistosomiasis; Anthelmintics; Praziquantel; Adult
PubMed: 38808760
DOI: 10.61409/V72026 -
Parasitology Research Dec 2023The One-Health approach recognizes the intricate connection between human, animal, and environmental health, and that cooperative effort from various professionals... (Review)
Review
The One-Health approach recognizes the intricate connection between human, animal, and environmental health, and that cooperative effort from various professionals provides comprehensive awareness and potential solutions for issues relating to the health of people, animals, and the environment. This approach has increasingly gained appeal as the standard strategy for tackling emerging infectious diseases, most of which are zoonoses. Treatment with anthelmintics (AHs) without a doubt minimizes the severe consequences of soil-transmitted helminths (STHs); however, evidence of anthelmintic resistance (AR) development to different helminths of practically every animal species and the distinct groups of AHs is overwhelming globally. In this regard, the correlation between the application of anthelmintic drugs in both human and animal populations and the consequent development of anthelmintic resistance in STHs within the context of a One-Health framework is explored. This review provides an overview of the major human and animal STHs, treatment of the STHs, AR development and drug-related factors contributing towards AR, One-Health and STHs, and an outline of some One-Health strategies that may be used in combating AR.
Topics: Animals; Humans; Helminthiasis; Soil; One Health; Anthelmintics; Helminths
PubMed: 38114766
DOI: 10.1007/s00436-023-08088-8 -
Scientific Reports Dec 2023Parasitic roundworms cause significant sickness and mortality in animals and humans. In livestock, these nematodes have severe economic impact and result in losses in...
Parasitic roundworms cause significant sickness and mortality in animals and humans. In livestock, these nematodes have severe economic impact and result in losses in food production on a global scale. None of the currently available drugs ideally suit all treatment circumstances, and the development of drug-resistant nematode strains has become a challenge to control the infection. There is an urgent need to develop novel anthelmintic compounds. According to our previous report, N-methylbenzo[d]oxazol-2-amine (1) showed anthelmintic activity and lowest cytotoxicity. In this study, in vivo anthelmintic properties were evaluated using Trichinella spiralis infected mice. Toxicity was evaluated using the rats and mode of action using molecular docking and metabolomics approaches. The in vivo results demonstrate that a dose of 250 mg/kg reduced the T. spiralis abundance in the digestive tract by 49%. The 250 mg/kg Albendazole was served as control. The relatively low acute toxicity was categorized into chemical category 5, with an LD greater than 2000 mg/kg body. Molecular docking analysis showed the T. spiralis tubulin beta chain and glutamate-gated channels might not be the main targets of compound 1. Metabolomics analysis was used to explain the effects of compound 1 on the T. spiralis adult worm. The results demonstrated that compound 1 significantly up-regulated the metabolism of purine, pyrimidine and down-regulated sphingolipid metabolism. In conclusion, compound 1 could be a potential molecule for anthelmintic development. The bioavailability, pharmacokinetics, and absorption of this compound should be studied further to provide information for its future efficacy improvement.
Topics: Humans; Mice; Rats; Animals; Molecular Docking Simulation; Anthelmintics; Albendazole; Nematoda; Trichinella spiralis
PubMed: 38129499
DOI: 10.1038/s41598-023-50305-y -
The Journal of Antimicrobial... Jan 2024
Topics: Humans; Artesunate; Artemisinins; Malaria, Falciparum
PubMed: 38019671
DOI: 10.1093/jac/dkad366 -
Current Opinion in Infectious Diseases Oct 2023Cystic echinococcosis is a neglected zoonosis for which humans are dead end hosts. It is not only widely distributed in sheep rearing areas of low-income and... (Review)
Review
PURPOSE OF REVIEW
Cystic echinococcosis is a neglected zoonosis for which humans are dead end hosts. It is not only widely distributed in sheep rearing areas of low-income and middle-income countries but also has a significant presence in wealthy countries, for example, in Europe. It results in considerable morbidity, and its current management is far from optimal. Medical management is with a benzimidazole, with the addition of praziquantel under some circumstances.
RECENT FINDINGS
Interest in mebendazole as an anticancer drug has stimulated research into new drug formulations to improve bioavailability and possibly reduce inter-individual variability in in-vivo drug levels, which may help its activity against cystic echinococcosis. Further evidence to support administration of albendazole with a fatty meal has been provided. GlaxoSmithKilne (GSK) has agreed to extend its albendazole donation programme to include echinococcosis. The search for new drugs has focussed on natural products, such as essential oils and on repurposing of existing drugs licensed for human use against other conditions.
SUMMARY
The medical treatment of cystic echinococcosis remains sorely neglected, with no new drugs for almost 40 years. We need a better understanding of how to use the drugs we do have, whilst seeking new ones. Drug repurposing may be the best pathway.
Topics: Humans; Animals; Sheep; Albendazole; Echinococcosis; Zoonoses; Europe; Mebendazole
PubMed: 37593991
DOI: 10.1097/QCO.0000000000000947