Leishmaniosis is a parasitic infection spreads to humans by sand flies. Over 20 different species of Leishmania are responsible for the disease, which infect over 14 million people around the world. Chemotherapy is one of the most effective treatments for leishmaniosis, however it is restricted by the high cost and/or toxicity. In this study, the possible effect of artemisinin (ART) was detected on intracellular amastigotes of Iraqi strain of Leishmania donovani in ex vivo condition in U937 macrophage cell line. Gene expression of inducible nitric oxide synthase (iNOS) in U937 macrophage was investigated, before and after treatment with artemisinin. Kinetic result by real-time PCR demonstrated that the iNOS expression folding reached the maximum at concentration of 500 μM after 24 hours, at 750 μM after 48 hours and at 1000 μM after 72 hours, which was 56, 11, and 6, respectively. The copy number of iNOS gene expression was also significantly higher in treated infected U937 cells compared to both non-treated-infected cells and intact macrophages, under different concentration of ART along the three times of follow-up. Moreover, stained macrophages with fluorescent DAPI proved that the percentage of intracellular infective amastigotes was decreased to the minimum in treated U937 cells, in comparison to non-treated cells. The minimal amastigote-invasion percentage was recorded at 1000 μM, which was 26%, 27%, 21% compared to 61%, 87%, 75% in untreated cells after 24, 48, 72 hours respectively. These findings demonstrated ART positive efficacy against iNOS expression and this compound can be further studied as novel therapeutic rather than toxic available chemotherapies.
Visceral leishmaniasis is a neglected tropical disease on the rise in different regions of Iraq, especially in areas with poor hygiene and among refugee populations. The effectiveness of existing chemotherapy for leishmaniasis is constrained by its high toxicity, cost, and the development of drug resistance. The current research examined various concentrations (ranging from 125 to 1000 μM) of lupeol to evaluate its ability to boost the generation of nitric oxide, which has anti-leishmanial properties, in an ex-vivo macrophage model. Griess assay was used to detect the nitric oxide (NO) production in Leishmania donovani infected U937 cell-line macrophages along 24 and 48 hours post treated. The nitric oxide concentration was signifi
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Leishmania species are the causative agent of a tropical disease known as leishmaniasis. Previous studies on the old world species Leishmania major, showed that the amastigotes form which resides inside the macrophage of the vertebrate host, utilize host’s sphingolipids for survival and proliferation. In this study, gene expression of serine palmitoyltransferase (SPT) subunit two (MmLCB2) of the mouse macrophage cell line (RAW264.7), which is the first enzyme in the de novo sphingolipid biosynthesis, was detected in both infected and non-infected macrophages. This was detected under condition where available sphingolipid was reduced, with the new world species Leishmania mexicana. Results of qPCR analysis showed that there was no differen
... Show MoreDespite extensive investigations, an effective treatment for sepsis remains elusive and a better understanding of the inflammatory response to infection is required to identify potential new targets for therapy. In this study we have used RNAi technology to show, for the first time, that the inducible lysophosphatidylcholine acyltransferase 2 (LPCAT2) plays a key role in macrophage inflammatory gene expression in response to stimulation with bacterial ligands. Using siRNA- or shRNA-mediated knockdown, we demonstrate that, in contrast to the constitutive LPCAT1, LPCAT2 is required for macrophage cytokine gene expression and release in response to TLR4 and TLR2 ligand stimulation but not for TLR-independent stimuli. In addition, cells transfe
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This study has evaluated the humoral immune response in Golden Hamsters experimentally infected with Leishmania donovani along (4) times of follow up (15, 30, 60, 90) days after infection. Indirect haemagglutination test was used to determine the antibody titer through the various stages of the study. Also the progress of the infection was studied depending on some of the visceral changes caused by the parasite, like weight of liver, length & weight of spleen & the count of Leishmania parasites in spleen were measured. Results has shown that there was an increase in antibody titer & the maximum value was recorded at the 4th day of follow up (90 days after infection) as well as that there was an increase in the length of the spleen, weight
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The clinical spectrum of cutaneous leishmaniasis (CL), an intracellular parasitic pathogen, ranges from a single sore healing to chronic crusty lesions with a manifestation of treatment resistance. The complicated interaction between Leishmania bodies and the early immune response, including innate and adaptive mechanisms, determines the evolution of nodules. This study examined the levels of the chemoattractant interleukin 8 (IL-8), pro-inflammatory nitric oxide (NO), and immunoregulatory macrophage inhibitory factor (MIF) in the serum of subjects recently diagnosed with cutaneous leishmaniasis, in parallel with patients being monitored during consecutive sodium stibogluconate (Pentostam) treatment. A total of 161 serum samples of newly di
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Visceral leishmaniosis is one of the most fatal old-world neglected disease with estimated 90 thousand worldwide cases emerge each year. In Iraq, the cutaneous and visceral form are endemic but available chemotherapies are either toxic with diverse side effects, expensive available drugs or parasite …
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Leishmania is auxotroph to folic acid,antifolates drug inhibit the synthesis and conversion of folate derivatives. In this study, cytotoxic effect of methotrexate was investigated on the procyclic promastigotes proliferation of L. donovani. The results showed a significant (p ≥ 0.05) difference in growth of treated groups at high concentrations (1000, 500, 250, 125.5) μM after 24, 48 hrs., while at 72 hrs. significant difference was observed at all concentration. The IC50 values was measurable after 24, 48 and 72 hrs. and it was 174.238, 52.283 and 109.175 μM, respectively. The present study showed the cytotoxic effect of methotrexate on the proliferation of promastigotes of the visceral type of Leishmania.
In the current study, different concentrations of miltefosine drug, which is the first effective and safe oral treatment for visceral leishmaniasis, was evaluated against L. donovani promastigotes in comparison with pentosam drug. Direct counting microscopic assay was used to find 50% inhibitory concentration (IC50) of miltefosine and pentostam against L. donovani promastigotes. The IC50 of miltefosine drug was 45.42μg/ml, 46.76μg/ml and 36.68μg/ml after 24 hr, 48hr and 72hr respectively, In comparison with IC 50 of pentostam drug was 75.39 μg/ml after 72hr. There were significant differences (P˂0.05) between IC50 values of miltefosine and pentostam drugs from first day to third day.