The current in vivo models for the utility and discovery of new potential anti-leishmanial drugs targeting Cutaneous Leishmaniasis (CL) differ vastly in their immunological responses to the disease and clinical presentation of symptoms. Animal models that show similarities to the human form of CL after infection with Leishmania should be more representative as to the effect of the parasite within a human. Thus, these models are used to evaluate the efficacy of new anti-leishmanial compounds before human clinical trials. Current animal models aim to investigate (i) host-parasite interactions, (ii) pathogenesis, (iii) biochemical changes/pathways, (iv) in vivo maintenance of parasites, and (v) clinical evaluation of drug candidates. This review focuses on the trends of infection observed between Leishmania parasites, the predictability of different strains, and the determination of parasite load. These factors were used to investigate the overall effectiveness of the current animal models. The main aim was to assess the efficacy and limitations of the various CL models and their potential for drug discovery and evaluation. In conclusion, we found that the following models are the most suitable for the assessment of anti-leishmanial drugs: L. major-C57BL/6 mice (or-vervet monkey, or-rhesus monkeys), L. tropica-CsS-16 mice, L. amazonensis-CBA mice, L. braziliensis-golden hamster (or-rhesus monkey). We also provide in-depth guidance for which models are not suitable for these investigations.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4559374PMC
http://dx.doi.org/10.1371/journal.pntd.0003889DOI Listing

Publication Analysis

Top Keywords

anti-leishmanial drugs
12
animal models
12
models
9
current vivo
8
vivo models
8
drugs targeting
8
targeting cutaneous
8
cutaneous leishmaniasis
8
current animal
8
models suitable
8

Similar Publications

Leishmaniasis is a neglected disease that remains with a limited number of drugs available for chemotherapy and has an increased drug resistance that affects treatment outcomes. Metal-based drugs such as cyclopalladated complex [Pd(dmba)(μ-N)] (CP2), a Leishmania topoisomerase IB inhibitor involved in calcium dysregulation and mitochondrial dysfunction of the parasite, had been an alternative to outline the appearance of chemoresistance. To identify new molecular targets and point out possible resistance mechanisms, a CP2-resistant Leishmania amazonensis (LaR) was selected by stepwise exposure to increasing drug pressure until a line capable of growth in 13.

View Article and Find Full Text PDF

Protozoan parasite infections, particularly leishmaniasis, present significant public health challenges in tropical and subtropical regions, affecting socio-economic status and growth. Despite advancements in immunology, effective vaccines remain vague, leaving drug treatments as the primary intervention. However, existing medications face limitations, such as toxicity and the rise of drug-resistant parasites.

View Article and Find Full Text PDF

In vitro and in silico approaches manifest the anti-leishmanial activity of wild edible mushroom .

In Silico Pharmacol

December 2024

Laboratory of Cell and Molecular Biology, Department of Botany, Centre of Advanced Study, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, 700019 India.

Visceral Leishmaniasis, caused by is the second most deadly parasitic disease, causing over 65,000 deaths annually. Synthetic drugs available in the market, to combat this disease, have numerous side effects. In this backdrop, we aim to find safer antileishmanial alternatives with minimal side effects from mushrooms, which harbour various secondary metabolites with promising efficacy.

View Article and Find Full Text PDF
Article Synopsis
  • Amphotericin B (AmB) is a strong antifungal and antiparasitic drug that kills leishmanial parasites by disrupting their cell membranes, making it important to study its effects on parasites like Leishmania orientalis to understand potential drug resistance.
  • This study involved exposing a specific Leishmania orientalis strain to AmB and analyzing genetic changes through sequencing methods, focusing on single nucleotide polymorphisms (SNPs) and gene expression changes.
  • The results indicated no significant chromosomal alterations post-treatment, but a higher incidence of SNPs in the control group, along with the downregulation of key genes, suggesting complex regulatory mechanisms might contribute to AmB resistance in this strain.
View Article and Find Full Text PDF

Anti-leishmanial therapies: overcoming current challenges with emerging therapies.

Expert Rev Anti Infect Ther

December 2024

Centre of Experimental Medicine and Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.

Introduction: Leishmaniasis, including visceral, cutaneous, and mucocutaneous forms, present a major health challenge in tropical regions. Current antileishmanial medications has significant limitations, creating a critical need for novel therapies that are safe and cost-effective with a shorter duration of treatment.

Areas Covered: This review explores the critical aspects of existing antileishmanial therapy and targets for future therapeutic developments.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!