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      Antileishmanial activity of a mixture of Tridax procumbens and Allium sativum in mice Translated title: Activité antileishmaniale d’un mélange de Tridax procumbens et Allium sativum chez la souris

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          Abstract

          We tested a mixture of Tridax procumbens, known for its direct action against Leishmania mexicana, and Allium sativum, known for its immunomodulatory effect, as an alternative to treat cutaneous leishmaniasis. Acute oral toxicity was tested with the Up-and-Down Procedure (UDP) using a group of healthy mice administered with either T. procumbens or A. sativum extracts and compared with a control group. Liver injury and other parameters of toxicity were determined in mice at day 14. The in vivo assay was performed with mice infected with L. mexicana promastigotes and treated with either a mixture of T. procumbens and A. sativum or each extract separately. The thickness of the mice’s footpads was measured weekly. After the 12-week period of infection, blood samples were obtained by cardiac puncture to determine the total IgG, IgG1 and IgG2a immunoglobulins by a noncommercial indirect ELISA. We showed that the mixture of T. procumbens and A. sativum extracts was better at controlling L. mexicana infection while not being toxic when tested in the acute oral toxicity assay in mice. An increase in the ratio of IgG2a/IgG1 indicated a tendency to raise a Th1-type immune response in mice treated with the mixture. The mixture of T. procumbens and A. sativum extracts is a promising natural treatment for cutaneous leishmaniasis and its healing effects make it a good candidate for a possible new phytomedicine.

          Translated abstract

          Nous avons testé un mélange de Tridax procumbens, dont l’action directe contre le parasite Leishmania mexicana est connue, et d’ Allium sativum, dont l’effet immunomodulateur est connu, comme une alternative pour traiter la leishmaniose cutanée. La toxicité orale aiguë a été testée avec la procédure Up and Down (UDP) sur un groupe de souris saines auxquelles ont été administrés soit des extraits de T. procumbens, soit des extraits de A. sativum, comparé à un groupe de contrôle. Les lésions hépatiques et d’autres paramètres de toxicité ont été déterminés au 14ème jour. L’essai in vivo a été réalisé avec des souris infectées avec L. mexicana et traitées soit avec un mélange de T. procumbens et A. sativum, soit avec les 2 extraits séparés. L’épaisseur des coussinets plantaires des souris a été mesurée une fois par semaine. Douze semaines après l’infection, un échantillon de sang a été prélevé par ponction cardiaque et les quantités totales d’immunoglobulines IgG, IgG1, et IgG2 ont été déterminées par ELISA indirect non commercial. Nous avons pu montrer que le mélange d’extraits de T. procumbens et A. sativum contrôlait mieux l’infection tout en n’étant pas toxique lors de l’essai de toxicité orale aiguë chez la souris. L’augmentation du ratio IgG2a/IgG1 a permis d’indiquer une tendance à augmenter une réponse immunitaire de type Th1 dans les souris traitées avec ce mélange. Le mélange des extraits de T. procumbens et A. sativum est un traitement naturel prometteur pour la leishmaniose cutanée et ses effets curatifs en font un bon candidat pour un possible nouveau phytomédicament.

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          Most cited references 22

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          Increasing failure of miltefosine in the treatment of Kala-azar in Nepal and the potential role of parasite drug resistance, reinfection, or noncompliance.

          Miltefosine (MIL), the only oral drug for visceral leishmaniasis (VL), is currently the first-line therapy in the VL elimination program of the Indian subcontinent. Given the paucity of anti-VL drugs and the looming threat of resistance, there is an obvious need for close monitoring of clinical efficacy of MIL. In a cohort study of 120 VL patients treated with MIL in Nepal, we monitored the clinical outcomes up to 12 months after completion of therapy and explored the potential role of drug compliance, parasite drug resistance, and reinfection. The initial cure rate was 95.8% (95% confidence interval [CI], 92.2-99.4) and the relapse rate at 6 and 12 months was 10.8% (95% CI, 5.2-16.4) and 20.0% (95% CI, 12.8-27.2) , respectively. No significant clinical risk factors of relapse apart from age <12 years were found. Parasite fingerprints of pretreatment and relapse bone marrow isolates within 8 patients were similar, suggesting that clinical relapses were not due to reinfection with a new strain. The mean promastigote MIL susceptibility (50% inhibitory concentration) of isolates from definite cures was similar to that of relapses. Although more tolerant strains were observed, parasite resistance, as currently measured, is thus not likely involved in MIL treatment failure. Moreover, MIL blood levels at the end of treatment were similar in cured and relapsed patients. Relapse in one-fifth of the MIL-treated patients observed in our study is an alarming signal for the VL elimination campaign, urging for further review and cohort monitoring.
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            Cross-protective efficacy of a prophylactic Leishmania donovani DNA vaccine against visceral and cutaneous murine leishmaniasis.

            The fucose-mannose ligand (FML) complex of Leishmania donovani is a promising vaccine candidate against murine and canine visceral leishmaniasis, and its main component is a 36-kDa nucleoside hydrolase (NH36). In this study, we tested the immune response and protection induced by the purified FML, the recombinant NH36 (rNH36), and NH36 DNA vaccines against the agents of visceral (L. chagasi) and cutaneous (L. mexicana) leishmaniasis in BALB/c mice. Mice developed weak humoral response to the vaccines alone, except for those immunized with FML. However, all three vaccine groups presented elevated immunoglobulin G (IgG), IgG1, and IgG2a levels after infection with L. chagasi, whereas no differences were observed between vaccine and control groups after infection with L. mexicana. A strong intradermal reaction to L. donovani and L. mexicana antigens was observed in mice immunized with rNH36 or FML, whereas mice immunized with NH36 DNA only reacted against L. donovani antigens. Experimental infection of immunized mice demonstrated that FML and rNH36 induced significant protection against L. chagasi infection with reductions in parasite loads of 79%. FML also conferred partial protection against L. mexicana infection. The best protection was observed in mice immunized with the VR1012-NH36 DNA vaccine, which induced an 88% reduction in L. chagasi parasite load and a 65% reduction in L. mexicana lesion size. Fluorescence-activated cell sorting analysis indicated the DNA vaccine induced a two- to fivefold increase in gamma interferon-producing CD4(+) T cells, indicating a Th1-type immune response. Our results showed that the NH36 DNA vaccine induced a strong immunoprotection against visceral and cutaneous leishmaniasis, suggesting that this DNA vaccine represents a very good candidate for use against several Leishmania species.
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              Efficacy of Co-administration of Garlic Extract and Metformin for Prevention of Gentamicin–Renal Toxicity in Wistar Rats: A Biochemical Study

              Background: Gentamicin (GM) nephrotoxicity has been related to oxidative stress. Garlic and metformin (MF) have anti-oxadant activity and therefore, this study was aimed to evaluate the preventive and curative effects of garlic, MF and their combination on GM indeced tubular toxicity in Wistar rats. Methods: In a pre-clinical study, 70 male Wistar rats were randomly designated into 7 groups of 10 and treated as follows: Group 1: Received saline for 20 days. Group 2: Were injected 100 mg/kg/d of GM intraperitoneally (ip), for 10 days and saline for 10 more days. Group 3: Received GM for 10 days then 20 mg/kg garlic ip for the next 10 days. Group 4: Received GM for 10 days and MF (100 mg/kg) orally for the next 10 days. Group 5: Received GM for 10 days and a combination of MF and garlic for the next 10 days (100 and 20 mg/kg, respectively). Group 6: The same as group 5but with half-doses of MF and Garlic. Group 7: Received GM for 10 days together with a combination ofMF and garlic. On 20th day of the experiment the serum blood urea nitrogen (BUN) and creatinine (Cr) were measured and compared in different groups. Results: GM injection significantly increased the serum BUN and Cr (P < 0.05). Administration of MF, garlic or their combination with or after injection of GM (high doses) could atenuate BUN and Cr. Conclusions: The results indicate that MF and garlic or their combination have curative and protective activity against GM nephrotoxicity.
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                Author and article information

                Journal
                Parasite
                Parasite
                parasite
                Parasite
                EDP Sciences
                1252-607X
                1776-1042
                2014
                10 April 2014
                : 21
                : ( publisher-idID: parasite/2014/01 )
                Affiliations
                [1 ] Laboratorio de Parasitología, Centro de Investigaciones Regionales “Dr. Hideyo Noguchi”, Universidad Autónoma de Yucatán (CIR-UADY) Avenida Itzáes # 490 × Calle 59 Colonia Centro 97000 Mérida, Yucatán México
                [2 ] Centro de Investigación Científica de Yucatán (CICY) Calle 43 No. 130, Col. Chuburná de Hidalgo 97200 Mérida, Yucatán México
                Author notes
                [* ]Corresponding author: gleon@ 123456uady.mx
                Article
                parasite130109 10.1051/parasite/2014016
                10.1051/parasite/2014016
                3980668
                24717526
                © R. Gamboa-Leon et al., published by EDP Sciences, 2014

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Page count
                Figures: 3, Tables: 1, Equations: 0, References: 32, Pages: 7
                Categories
                Research Article

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