title: In vivo and in vitro antileishmanial activity of Bungarus caeruleus snake venom through alteration of immunomodulatory activity.
abstract: Leishmaniasis threatens more than 350 million people worldwide specially in tropical and subtropical region. Antileishmanial drugs that are currently available have various limitations. The search of new drugs from natural products (plants, animals) possessing antileishmanial activity is ventured throughout the world. The present study deals with the antileishmanial activity of Bungarus caeruleus snake venom (BCV) on in vitro promastigotes and amastigotes of Leishmania donovani parasite and leishmania infected BALB/c mice. The effect of BCV on peritoneal macrophage, release of cytokines from the activated macrophages, production of nitric oxide, reactive oxygen species and cytokines were studied in vivo and in vitro. IC50 value of BCV on L. donovani promastigote was 14.5 μg/ml and intracellular amastigote was 11.2 μg/ml. It activated peritoneal macrophages, significantly increased cytokines and interleukin production. BCV (20 μg/kg and 40 μg/kg body weight of mice) decreased parasite count by 54.9% and 74.2% in spleen and 41.4% and 60.4% in liver of infected BALB/c mice. BCV treatment significantly increased production of TNF-α, IFN-γ, ROS, NO in infected mice. Histological studies showed decreased granuloma formation in treated liver as compared with control. Liver and spleen structure was partially restored due to BCV treatment in infected mice. The present study revealed that BCV possessed antileishmanial activity against L. donovani parasite in vivo and in vitro and this activity was partly mediated through immunomodulatory activity involving macrophages.
authors.affiliation: Cell Biology and Physiology Division, Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Kolkata 700032, India.
authors.forename: Shamik
authors.initials: S
authors.lastname: Bhattacharya
authors.forename: Prasanta
authors.initials: P
authors.lastname: Ghosh
authors.forename: Tripti
authors.initials: T
authors.lastname: De
authors.forename: Antony
authors.initials: A
authors.lastname: Gomes
authors.forename: Aparna
authors.initials: A
authors.lastname: Gomes
authors.forename: Sandhya Rekha
authors.initials: SR
authors.lastname: Dungdung
mesh_terms: D000818:Animals; D000967:Antimony Sodium Gluconate / Q000494:pharmacology / Q000627:therapeutic use; D000981:Antiprotozoal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002038:Bungarotoxins / Q000494:pharmacology* / Q000627:therapeutic use; D017838:Bungarus; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D005260:Female; D020128:Inhibitory Concentration 50; D007371:Interferon-gamma / Q000378:metabolism; D007893:Leishmania donovani / Q000187:drug effects*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000276:immunology; D008099:Liver / Q000469:parasitology / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology / Q000469:parasitology; D008297:Male; D008647:Mesocricetus; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013154:Spleen / Q000469:parasitology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000981:Antiprotozoal Agents; D002038:Bungarotoxins; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007371:Interferon-gamma; D000967:Antimony Sodium Gluconate
keywords: Antileishmania; BCV; Bungarus caeruleus; Bungarus caeruleus venom; FCS; Immunomodulatory activity; Leishmania donovani; MTT; Macrophage; NO; PBS; ROS; SAG; Snake venom; fetal calf serum; nitric oxide; phosphate buffer saline; reactive oxygen species; sodium antimony gluconate; thiazolyl blue tetrazolium bromide