The Fraction of the Snake Venom, Its Leishmanicidal Effect, and the Stimulation of an Anti-Leishmania Response in Infected Macrophages

Abstract

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.

Exploring the global animal biodiversity in the search for new drugs - Reptiles

“…Importantly, the antileishmanial effects have been associated with perturbation of mitochondria, nuclei, and plasma membranes of the parasites [162,168] as well as the release of cytotoxic cytokines from host neutrophils against the parasites [170]. The latter observations were consistent with the cytotoxic effects of a fraction of the venom from the Central Asian cobra Naja naja oxiana (Elapidae) towards L. (L.) infantum promastigotes and amastigotes following stimulation of the immune system [171]. This venom also promoted the production of reactive oxygen species and apoptotic-like mechanisms, and inhibited the activity of arginase, a critical enzyme in the metabolism of Leishmania parasites [171].…”

Antiprotozoal Effect of Snake Venoms and Their Fractions: A Systematic Review

“…These diversities are attributed to diet [87,[91][92][93] or topography [94,95]. Other attributable factors include repetitions in toxin-encoding genes, production processes [96][97][98][99][100], and functional and structural diversifications [75,88,101,102]. For example, venom from Laticauda semifasciata (a sea snake) does not have a complex composition, and it has just two prominent families of proteins, 3FTxs and PLA2s.…”

“…In contrast, viperid venoms are made up of more significant fractions with enzymatic activities such as snake venom metalloproteinase and snake venom serine protease [84]. For instance, the venom of C. durissus terrificus is composed of amino acids, small peptides, carbohydrates, lipids, biogenic amines, and enzymes, whereas that of B. jararaca has peptides, serine, and metalloproteases as its constituents [75]. Hence, the activity of venoms varies with the difference in concentrations and compositions.…”

“…Aside from the role of snake species in the antiprotozoal effect, parasites also present contributing factors. Promastigotes and amastigotes are physiologically different in their sensitivity to drugs, with amastigotes having the greater capability to accumulate drugs [75]. Furthermore, Podešvová et al [52] reported that variations in the compositions of parasite membranes could also be responsible for the differences in the activities of snake venoms and their fractions.…”

“…Similarly, a need was reported to further investigate the fractions of B. jararaca and C.d. terrificus with antigiardial potential, suggesting that more research will provide details on the mechanisms of action [75].…”