acid-phosphatase and Schistosomiasis-mansoni

Schistosomiasis mansoni is one of the most important, but often neglected, tropical diseases transmitted by snails of the genus Biomphalaria. Control of the intermediate host snail plays a crucial role in preventing the spread of schistosomiasis. However, there is only one molluscicide, niclosamide, recommended by the World Health Organization. Niclosamide has been used for several decades but is toxic to non-target organisms. Therefore, it is necessary to optimize the scaffold of niclosamide and develop novel molluscicides with enhanced potency and decreased toxicity to non-target organisms.. In this study, a candidate compound was analyzed by nuclear magnetic resonance and mass spectrometry. The molluscicidal potential against Biomphalaria species and cercaricidal potential against S. mansoni were evaluated using the immersion method. Furthermore, the preliminary mechanism was studied through cellular enzyme tests and electron microscopy.. 5-chloro-2-[(2-chloro-4-nitrophenyl)carbamoyl]phenyl-4-methoxybenzoate (salicylanilidate), a novel salicylanilide ester derivative, was derived from niclosamide. The 50% lethal concentration to B. glabrata, B. straminea and B. pfeifferi was 0.261 mg/l, 0.172 mg/l and 0.241 mg/l, respectively. The effective dose required to completely kill S. mansoni cercariae was 0.625 mg/l for salicylanilidate and 0.125 mg/l for niclosamide. However, salicylanilidate was approximately 100-fold less toxic to the fish Danio rerio than niclosamide. Furthermore, salicylanilidate reduced the enzymatic activities of nitric oxide synthase (NOS), lactate dehydrogenase (LDH) and acetylcholinesterase (AChE) in the snail, demonstrating that it could affect neurohypophysis transmission and energy metabolism. Severe swelling in the tentacle and deformation of cilia in the tentacle and mantle were observed through scanning electron microscopy. The results of transmission electron microscopy showed that salicylanilidate could damage critical organelles in hepatopancreas tissues, including degeneration of the endoplasmic reticulum and vacuolization in mitochondria. In addition, transcriptional levels of superoxide dismutase (SOD), acid phosphatase (ACP) and NOS in the hepatopancreas were significantly downregulated as shown by real-time quantitative polymerase chain reaction (RT-PCR). These results indicated that the hepatopancreas is a primary target organ of salicylanilidate.. Salicylanilidate not only had deleterious effects on Biomphalaria species and S. mansoni cercariae but also showed very low toxicity to D. rerio, suggesting that it has broad potential applications.

Topics: Acetylcholinesterase; Acid Phosphatase; Animals; Biomphalaria; Cercaria; Cilia; Disease Vectors; Drug Discovery; Endoplasmic Reticulum; Hepatopancreas; L-Lactate Dehydrogenase; Microscopy, Electron, Scanning; Mitochondria; Molluscacides; Niclosamide; Nitric Oxide Synthase; Salicylanilides; Schistosoma mansoni; Schistosomiasis mansoni; Superoxide Dismutase

Histopathological, histochemical and immunohistochemical studies were carried out on the skeletal muscles of mice experimentally infected with Schistosoma mansoni throughout 20 weeks post infection. Histopathogical changes were detected from the 13th week post infection inspite of absence of Schistosoma mansoni eggs. There were definite enzymatic changes dehydrogenase, non specific esterase and acid and alkaline phosphatases. These changes started from the 14th week post infection. S. mansoni immune complex deposits were detected in the muscles from the 9th week post infection. Positive correlation was found between the degree of immune complex deposition and histopathological and histochemical changes. The study confirmed the role of immune complex in the pathogenesis of skeletal muscle lesion in Schistosoma mansoni infection (schistosomal myopathy).

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Antigen-Antibody Complex; Esterases; Immunohistochemistry; Mice; Muscle, Skeletal; Schistosomiasis mansoni; Succinate Dehydrogenase

Studies on human and murine isolates of Schistosoma mansoni, from Richard-Toll, Senegal, were carried out by isoelectric focusing in polyacrylamide gels. Seven enzyme systems; lactate dehydrogenase (LDH), malate dehydrogenase (MDH), glucose-6-phosphate dehydrogenase (G6PD), acid phosphatase (AcP), hexokinase (HK), glucose phosphate isomerase (GPI), and phosphoglucomutase (PGM), were used to compare the two isolates. All systems tested, apart from LDH, were found to be polymorphic for both isolates. Interestingly, one phenotype is more frequent than the remainder. The results show that there is no significant genetic variation between the S. mansoni isolates from man and the rodents, Arvicanthis niloticus and Mastomys huberti.

Topics: Acid Phosphatase; Animal Diseases; Animals; Genetic Variation; Glucose-6-Phosphate Isomerase; Glucosephosphate Dehydrogenase; Hexokinase; Humans; Isoelectric Focusing; L-Lactate Dehydrogenase; Malate Dehydrogenase; Phenotype; Phosphoglucomutase; Rats; Schistosoma mansoni; Schistosomiasis mansoni; Senegal