Background and aims::
Due to the lack of an effective vaccine and complexity of the control measures against vectors and reservoir hosts, the control of leishmaniasis depends primarily on chemotherapy. This study was aimed to assess the snake venom, Naja naja oxiana fraction 11(NNOV-F11) on L. infantum and its broad mode of action.
Methods::
A wide range of in vitro advanced assays including high-performance liquid chromatography (HPLC), MTT (3-[4, 5-Dimethylthiazol-2-yl]-2, 5diphenyltetrazolium bromide; Thiazolyl blue) and macrophage assays, quantitative real-time polymerase chain reaction (qPCR), flow cytometry and enzyme-linked immunosorbent assay (ELISA) on L. infantum pro-mastigote and amastigote stages were used. IC50 values of L. infantum stages, CC50 value and apoptosis were also analyzed.
Results::
The NNOV-F11 demonstrated strong antileishmanial activity against L. infantum stages in a dose-dependent man-ner compared to the untreated control group. Interleukin (IL)-12, TNF-α and iNOS genes expression as the indicators of T helper(h)1 response significantly increased; in contrast, the expression level of IL-10, as the representative of Th2 response significantly decreased (p ˂ 0.001). Reactive oxygen species (ROS) detection showed statistically a significant increase (p ˂ 0.001) after treatment with different concentrations of NNOV-F11, unlike arginase (ARG) activity which displayed a signif-icant reduction (p < 0.001).
Conclusion::
NNOV-F11 possesses a potent inhibitory effect on L. infantum stages with the multifunctional and broad mode of actions which promoted the immunomodulatory role, induced ROS production, stimulated apoptotic–like mechanisms and inhibited L-ARG activity which collectively led to the parasite death. Further studies are crucial to assess the effect of the fraction NNOV-F11 on animal models or clinical settings.
:
Studies have shown that selenium is an essential component of glutathione as an important antioxidant to reduce
oxidative stress and inhibit intracellular parasites’ growth. In contrast, calcium in cytosol of such parasites plays
a key role in entry of the parasite into the host cell and its primary motility. The present study was designed to
evaluate and compare glutathione peroxidase bioactivity effects post administration of selenium and calcium in
BALB/c mice infected by Toxoplasma gondii (Table 3)
Sixty BALB/c mice susceptible to T. gondii were randomly divided into twelve groups of case and control
groups. There were six control groups including two positive controls infected only with the paraites either 104
or 5×104
, non-infcetd and untreated groups, Treated controls were received only calcium, selenium, or both
respectively. Case groups were infected with 104
or 5×104
parasites. While each set of three case groups
separately received minerals alone or together. Mice were orally fed with 200 μg selenium, 50 μg calcium or
their combination for 7 days. Mice were infected by parasite’s tachyzoites. Sera of mice were kept and the
peritoneal macrophages were isolated for counting tachyzoites during infection.
The results showed that selenium unlike calcium was significantly effective in reducing Toxoplasma tachyzoites
compared to control groups. Moreover, glutathione peroxidase [GPX] activity was elevated in mice treated with
selenium and vice versa decreased in mice treated with calcium.
Administration of selenium unlike calcium reduced Toxoplasma tachyzoites proliferation by elevating
bioactivity of selenium-dependent detoxification enzyme, GPX.
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