Effect of varying the pharmaceutical formulation on the biochemical a vailability and immunological behaviour of schistosomicidal drug, Oxamniquine

Oxamniquine [OXQ] is one of schistosomicide specific for Schistosoma mansoni [S. mansoni] infection. The aim of this work was to encapsulate OXQ into a liposome. These liposomal formulations in order to exhibit long term prophylactic effect against S. mansoni. It was found that OXQ exhibited marked chemoprophylaxis effect when encapsulated in negatively charged liposomes. Pharmacokinetically, OXQ liposomes are perfectly targeted to the liver whereby they release oxamniquine in minute amounts over extended periods in the proximate of schistosomules, maturing in liver sinusoids. All animal groups were injected with either free oxamniquine, OXQ free liposomes or OXQ liposomes encapsulated, one, two or three months before infection by S. mansoni cercariae and were sacrificed 6 weeks post infection. It was found that OXQ liposomes had moderate normalization effect on liver enzymes, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and gamma glutamyl transferase in serum. Oxamniquine liposomes normalized A/G ratio and decreased the liver granuloma diameters. Infection increased the IgE and IgGl level, treatment with OXQ liposomes increased the level of IgG1 when given one or two months before infection, while free OXQ reduced IgG1 when given one month before infection and no significant change when given two months before infection. Treatment with different formulations to S. mansoni infected mice produced a significant decrease in IgE level after one and two months protection, while in normal animals there was an increase in IgG1 level after one month and no significant change after two months protection. So, it was concluded that OXQ in liposomal formulations is more efficient and safe than free drug in the protection against S. mansoni infection

Effect of perindopril alone and combined with praziquantel in murine Schistosoma mansoni

Murine schistosomiasis is a granulomatous disease associated with high serum and granulomatous angiotensin-1-converting enzyme [ACE] activity. Perindopril, a specific competitive inhibitor of ACE, was administered to mice infected with Schistosoma mansoni [S. mansoni] to determine whether this compound could inhibit granuloma ACE activity and modify the size of the granulomatous response to schistosoma eggs. Per-oral administration of perindopril for 4 weeks to 6th weeks old infected mice with peak granulomatous responses was carried out. Treated mice demonstrated a reduction in hepatic granuloma diameter by about 31% associated with a decrease in serum, spleen and hepatic granuloma ACE activity by about 36%, 64% and 65%, respectively, 12 weeks post infection. Also, there was an improvement of liver function tests. Mean diameters of synchronous pulmonary granulomas induced by pulmonary embolization of schistosome eggs into normal [115.4 Um +/- 2.4] or sensitized mice [129.4 Um +/- 5.3] were decreased [28% and 26%, respectively] by a similar dose of perindopril when administered 16 days post egg injection. It was concluded that perindopril may partially inhibit the granulomatous response to schistosome eggs and improve the pathological manifestations of schistosomiasis possibly through inhibition of the inflammatory mediator [ACE]. It is possible that ACE has an inflammatory role in granulomatous inflammation. Combined treatment with praziquantel enhanced the reduction recorded in the previous parameters examined

Effect of Eclipta alba alone and in addition to praziquantel in murine Schistosomiasis mansoni

Eclipta alba has been used in traditional medicine for treatment of liver cirrhosis and hepatitis. In this study, Eclipta alba was used alone and in combination with praziquantel. Four groups of Schistosoma mansoni [S. mansoni] infected mice were used and treatment was started 8 weeks post infection. The first was control untreated group, the second praziquantel in a dose of 500 mg/kg orally for 2 consecutive days, the third group treated with Eclipta alba [200 mg/kg for two weeks] and the last group received combined therapy. The results confirmed that Eclipta alba does not have curative properties against S. mansoni in infected mice. However, both alone and in combination with praziquantel, it decreased the level of alanine aminotransaminase [ALT] and leukotrein B4 [LTB4] in serum and the level of reduced glutathione [GSH] and malonaldehyde [MDA] in liver homogenate. It also reduced the hepatic granuloma diameter [37% and 40%, respectively, after 10 and 13 weeks post infection] and reduced the number of eosinophils in these granulomas. On the other hand, praziquantel [PZQ] produced 99% worm reduction and improved the level of ALT,GSH and MDA. The results suggested that Eclipta alba had anti-inflammatory and anti-hepatoprotective effect in Schistosoma mansoni infection and would be a useful treatment after praziquantel treatment