In vitro and in vivo antileishmanial efficacy of nitazoxanide against Leishmania donovani

Zhang, Ruiyan; Shang, Liming; Jin, Hongtao; Yong-kui, WU; Liu, Quan; Xia, Zhang; Wei, Feng; Zhu, Xingquan; Gao, Hongwei

doi:10.1007/s00436-010-1906-y

Cited by 24 publications

(16 citation statements)

References 22 publications

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“…The Leishmania isolate MHOM/CN/92/SC10H2 was originally obtained from Sichuan Province and maintained in our laboratory [22]. The parasite was grown in NNN medium at 24°C for 14 days.…”

Section: Methodsmentioning

confidence: 99%

The prevalence of canine Leishmania infantum infection in Sichuan Province, southwestern China detected by real time PCR

et al. 2011

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BackgroundVisceral leishmaniasis (VL) is endemic in western China, and becoming an important public health concern. Infected dogs are the main reservoir for Leishmania infantum, and a potential sentinel for human VL in endemic areas. In the present study we investigated the prevalence of Leishmania DNA in dogs from Wenchuan, Heishui and Jiuzhaigou County in Sichuan Province, southwestern China, which are important endemic areas of zoonotic VL, detected by real time PCR. The results will help to design control strategies against visceral leishmaniasis in dogs and humans.ResultsThe overall prevalence of Leishmania DNA in dogs was 24.8% (78/314) in Sichuan Province, with the positive rate of 23.5% (23/98) in Wenchuan County, 28.2% (20/71) in Heishui County, and 24.1% (35/145) in Jiuzhaigou County, and no significant difference was observed among the three counties (P > 0.05). The dogs were further allocated to different groups based on sexes, ages and external clinical symptoms. The logistic regression analysis revealed that a higher prevalence was found in older and external symptomatic dogs, compared to that of younger and asymptomatic dogs (P < 0.05).ConclusionsThe results revealed that L. infantum infection in dogs is widespread in Sichuan Province, southwestern China, which has a public health significance, due to its contribution to the transmission of the infection to humans by sandflies. It is necessary to take measures, including treatment or eradication of infected dogs, to control canine leishmaniasis, which could be helpful to reduce human VL in this area.

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“…The Leishmania isolate MHOM/CN/92/SC10H2 was originally obtained from Sichuan Province and maintained in our laboratory [22]. The parasite was grown in NNN medium at 24°C for 14 days.…”

Section: Methodsmentioning

confidence: 99%

The prevalence of canine Leishmania infantum infection in Sichuan Province, southwestern China detected by real time PCR

et al. 2011

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“…Failure of classic chemotherapy that lies on the use of antimonial compounds as well as risks of transmission of drug resistance highlight the priority to develop novel chemotherapeutic approaches to fight the disease (Ait-Oudhia et al 2011;Santos et al 2008). Current trials which show promising results cover natural and biologically active products (Karamian et al 2007; Morais et al 2011;Moreno et al 2011;Mussi et al 2007;Shakya et al 2011;Zhang et al 2010).…”

Section: Introductionmentioning

confidence: 98%

Leishmania major protein disulfide isomerase as a drug target

et al. 2011

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Leishmaniasis is a major health problem worldwide and tools available for their control are limited. Effective vaccines are still lacking, drugs are toxic and expensive, and parasites develop resistance to chemotherapy. In this context, new antimicrobials are urgently needed to control the disease in both human and animal. Here, we report the enzymatic and functional characterization of a Leishmania virulence factor, Leishmania major Protein disulfide isomerase (LmPDI) that could constitute a potential drug target. LmPDI possesses domain structure organization similar to other PDI family members (a, a', b, b' and c domains), and it displays the three enzymatic and functional activities specific of PDI family members: isomerase, reductase and chaperone. These results suggest that LmPDI plays a key role in assisting Leishmania protein folding via its capacity to catalyze formation, breakage, and rearrangement of disulfide bonds in nascent polypeptides. Moreover, Bacitracin, a reductase activity inhibitor, and Ribostamycin, a chaperone activity inhibitor, were tested in LmPDI enzymatic assays and versus Leishmania promastigote in vitro cultures and Leishmania amastigote multiplication inside infected THP-1-derived macrophages. Bacitracin inhibited both isomerase and reductase activities, while Ribostamycin had no effect on the chaperone activity. Interestingly, Bacitracin blocked in vitro promastigote growth as well as amastigote multiplication inside macrophages with EC(50) values of 39 μM. These results suggest that LmPDI may constitute an interesting target for the development of new anti-Leishmania drugs.

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“…For leishmaniasis, there are few new drugs in the pipeline, and the parasites resistance is increasing . In this context, the design of new delivery systems to be combined with conventional drugs aiming to reduce their toxicity (Ribeiro et al 2014a), or the use of synthetic molecules with validated antileishmanial activity being incorporated into these systems, could represent new promising strategies to obtain more effective and less toxic products (Neves et al 2010;Zhang et al 2010;Carvalho et al 2013;Ribeiro et al 2014b).…”

Section: Introductionmentioning

confidence: 98%

An 8-hydroxyquinoline-containing polymeric micelle system is effective for the treatment of murine tegumentary leishmaniasis

et al. 2016

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The current treatment of leishmaniasis has been hampered due to the high toxicity of the available drugs and long duration protocols, which often lead to its abandonment. In the present study, a poloxamer 407-based delivery system was developed, and a molecule, 8-hydroxyquinoline (8-HQN), was incorporated with it, leading to an 8-HQN/micelle (8-HQN/M) composition. Assays were performed to evaluate the in vitro antileishmanial activity of 8-HQN/M against Leishmania amazonensis stationary promastigotes. The cytotoxicity in murine macrophages and in human red cells, as well as the efficacy of the treatment in macrophages infected by parasites, was also assessed. This product was also evaluated for the treatment of murine tegumentary leishmaniasis, using L. amazonensis-infected BALB/c mice. To evaluate the in vivo efficacy of the treatment, the average lesion diameter (area) in the infected tissue, as well as the parasite load at the site of infection (skin), spleen, liver and draining lymph nodes were examined. Non-incorporated micelle (B-8-HQN/M) and the free molecule (8-HQN) were used as controls, besides animals that received only saline. The parasite burden was evaluated by limiting dilution and quantitative real-time PCR (qPCR) techniques, and immunological parameters associated with the treatments were also investigated. In the results, the 8-HQN/M group, when compared to the others, presented more significant reductions in the average lesion diameter and in the parasite burden in the skin and all evaluated organs. These animals also showed significantly higher levels of parasite-specific IFN-γ, IL-12, and GM-CSF, associated with low levels of IL-4 and IL-10, when compared to the saline, 8-HQN/M, and B-8-HQN groups. A predominant IL-12-driven IFN-γ production, against parasite proteins, mainly produced by CD4 T cells, was observed in the treated animals, post-infection. In conclusion, 8-HQN/M was highly effective in treating L. amazonensis-infected BALB/c mice and can be considered alone, or combined with other drugs, as an alternative treatment for tegumentary leishmaniasis. Graphical Abstract Therapeutic scheme and immunological and parasitological parameters developed in the present study.

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In vitro and in vivo antileishmanial efficacy of nitazoxanide against Leishmania donovani

Cited by 24 publications

References 22 publications

The prevalence of canine Leishmania infantum infection in Sichuan Province, southwestern China detected by real time PCR

The prevalence of canine Leishmania infantum infection in Sichuan Province, southwestern China detected by real time PCR

Leishmania major protein disulfide isomerase as a drug target

An 8-hydroxyquinoline-containing polymeric micelle system is effective for the treatment of murine tegumentary leishmaniasis

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