13 research outputs found
Anthelmintic Activity In Vivo of Epiisopiloturine against Juvenile and Adult Worms of Schistosoma mansoni
Schistosomiasis is a serious disease currently estimated to affect more that 207 million people worldwide. Due to the intensive use of praziquantel, there is increasing concern about the development of drug-resistant strains. Therefore, it is necessary to search for and investigate new potential schistosomicidal compounds. This work reports the in vivo effect of the alkaloid epiisopiloturine (EPI) against adults and juvenile worms of Schistosoma mansoni. EPI was first purified its thermal behavior and theoretical solubility parameters charaterised. In the experiment, mice were treated with EPI over the 21 days post-infection with the doses of 40 and 200 mg/kg, and 45 days post-infection with single doses of 40, 100 and 300 mg/kg. The treatment with EPI at 40 mg/kg was more effective in adult worms when compared with doses of 100 and 300 mg/kg. The treatment with 40 mg/kg in adult worms reduced parasite burden significantly, lead to reduction in hepatosplenomegaly, reduced the egg burden in faeces, and decreased granuloma diameter. Scanning electron microscopy revealed morphological changes to the parasite tegument after treatment, including the loss of important features. Additionally, the in vivo treatment against juvenile with 40 mg/kg showed a reduction of the total worm burden of 50.2%. Histopathological studies were performed on liver, spleen, lung, kidney and brain and EPI was shown to have a DL50 of 8000 mg/kg. Therefore EPI shows potential to be used in schistosomiasis treatment. This is the first time that schistosomicidal in vivo activity of EPI has been reported
Hematological parameters of Swiss mice treated with EPIIS by oral route.
<p>Hematological parameters of Swiss mice treated with EPIIS by oral route.</p
<i>In vitro</i> cytotoxicity assay with EPIIS.
<p>Adhesion indices of NIH-3T3 and HaCaT cells treated with EPIIS. The concentrations of EPIIS were 32 or 512 ÎĽg/mL and the adhered cell rates were measured every 30 min for 137 h.</p
Biochemical parameters in sera obtained from Swiss mice treated with EPIIS by oral route.
<p>Biochemical parameters in sera obtained from Swiss mice treated with EPIIS by oral route.</p
Physicochemical parameters through <i>in silico</i> analysis of EPIIS using pkCSM methodology.
<p>Physicochemical parameters through <i>in silico</i> analysis of EPIIS using pkCSM methodology.</p
Effect on egg development and on Stoll egg count of a single dose 100 mg/kg of EPIIS administered to mice harboring a 60-day-old adult <i>S</i>. <i>mansoni</i> infection.
<p><b>(A)</b> EPIIS effect on egg development stages (oogram) <b>(B)</b> Effect on Stoll egg count. Points represent data from individual mice that were infected and treated with EPIIS, or infected and untreated (control). The horizontal bars represent median values. **<i>P</i> < 0.01 and ***<i>P</i> < 0.001 compared with untreated groups.</p
Scanning electron microscopy of <i>S</i>. <i>mansoni</i> adults retrieved 48 h after treatment with EPIIS (100 mg/kg).
<p><b>A-D</b>: Control group—untreated; <b>E–L:</b> Male and female worms. The arrows show damage to tegument with reduction in the size of the spines, and damage to the oral and ventral suckers in male worms, followed by body corrugation in female worms. Image bar scale: (<b>A</b>) 100X___10 kv; (<b>B</b>) 120X ___10 kv; (<b>C-D</b>) 180X ___10 kv; (<b>E-F</b>) 127X ___10 kv; (<b>G-H</b>) 250X___10 kv; (<b>I- L)</b> 350X___10 kv.</p
Epiisopilosine alkaloid has activity against <i>Schistosoma mansoni</i> in mice without acute toxicity - Fig 9
<p><b>Photomicrographs of histological sections of liver (A1, A2), spleen (B1, B2), kidney (C1, C2), lung (D1, D2) and brain (E1, E2) obtained from Swiss mice of control group (first column) and group treated with 2000 mg/kg EPIIS (second column).</b> Hematoxylin & eosin, 400 X magnification, bars = 50 ÎĽm.</p