Schistosomicidal and hepatoprotective activity of gamma-aminobutyric acid (GABA) alone or combined with praziquantel against Schistosoma mansoni infection in murine model.

OBJECTIVE: This study aimed to evaluate the efficacy of gamma-aminobutyric acid (GABA) alone or combined with praziquantel (PZQ) against Schistosoma (S) mansoni infection in a murine model. METHODS: Five groups, 8 mice each, were studied; GI served as normal controls; GII: S. mansoni-infected control group and the other three S. mansoni-infected groups received drug regimens for 5 consecutive days as follows GIII: Infected-PZQ treated group (200 mg/kg/day); GIV: Infected-GABA treated group (300 mg/kg/day) and GV: Infected-PZQ-GABA treated group (100 mg/kg/day for each drug). All animal groups were sacrificed two weeks later and different parasitological, histopathological and biochemical parameters were assessed. RESULTS: Combined GABA-PZQ treated group recorded the highest significant reduction in all parasitological, histopathological and biochemical parameters followed by PZQ and finally GABA groups. Combined GABA-PZQ treatment led to the complete disappearance of immature eggs and marked reduction of deposited eggs in liver tissues and improved liver pathology. Significant improvement in hepatic oxidative stress levels, serum albumin and total protein in response to GABA treatment alone or combined with PZQ. CONCLUSION: GABA had schistosomicidal, hepatoprotective and antioxidant activities against S. mansoni infection, GABA disrupted parasite pairing and activity, reduced the total number of worms recovered and the number of ova in the tissues. GABA may be considered an adjuvant therapy to potentiate PZQ antiparasitic activity and eradicate infection-induced liver damage and oxidative stress.

'de Novo' repurposing of Daflon as anti-intestinal parasitic drug in experimental giardiasis.

BACKGROUND: There is a necessity to develop or discover an alternative drug to combat the drug resistance by Giardia duodenalis and minimize the multiple doses and frequency of the conventional drug administration. Progressive repositioning or 'repurposing' of drugs has become widespread due to economic circumstances and medical emergency needs. Daflon 500 mg (DFL) is a natural product used safely as a nutrient supplement and an antidiabetic drug in many European countries and the US. OBJECTIVE: This study aimed at investigating the efficiency of DFL, in vivo, in a murine model as a safe alternative or co-drug for giardiasis. MATERIALS AND METHODS: Swiss Albino mice (n = 32) were inoculated with 1X104Giardia cysts and assigned to four groups: One group was the infected non-treated control mice and three experimental groups that were treated differently, either with Metronidazole (MTZ), DFL, or combined therapy of DFL/MTZ. Also, eight normal mice served as a control group. All mice were sacrificed 13 days post-infection for the parasitic, histopathological, and oxidative stress analysis. RESULTS: MTZ, DFL, and the combined therapy significantly reduced the number of trophozoites and cysts compared to their counterparts of the infected mice. The histopathological analysis of the small intestines of the mice treated with the combined therapy retained typical intestinal architecture and normal levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione. CONCLUSION: This study indicated promising actions of Daflon 500 as an anti-giardial drug, and the results demonstrated its potential effect in improving the intestinal epithelial tissue and disturbing the Giardia stages when it was taken collectively with Metronidazole.

Prophylactic versus therapeutic role of the transplanted CD34+ Umbilical Cord Blood Stem Cells and Wharton Jelly Mesenchymal Stem Cells in early / acute hepatic S. mansoni granulomas reversal in mice; a novel approach.

PURPOSE: Praziquantel (PZQ) is the conventional antibilharzial agent. Nevertheless, no antibilharzial prophylactic agents or 100% curable therapy approved and no reported data about use of human CD34+ Umbilical Cord Blood Stem Cells (CD34+UCBSCs) or Wharton Jelly Mesenchymal Stem Cells (WJMSCs) in prevention and/or complete eradication of acute S.mansoni granulomas in liver. We aimed to study possible prophylactic vs therapeutic role of human CD34+UCBSCs and WJMSCs in acute hepatic bilharzial granulomas in pre vs post-infected mice. METHODS: Seventy mice were divided into 7 groups (10 mice each): Normal, S.mansoni-infected, post-infected PZQ-treated, CD34+UCBSCs pre and post-infected, WJMSCs pre and post-infected. Serological, parasitological, histopathological evaluation using OCT4 & TGFB immunohistochemistry and quantitative image analysis assessment of TGFB-stained fibrogenesis in liver granulomas performed. RESULTS: Histopathologically, surprisingly and significantly, the prophylactic pre-infection stem cells (CD34+UCBSCs and WJMSCs) & similarly the post-infection CD34+UCBSCs treatment revealed eradication/reversal of the entire granulomas and no fibrosis. Moreover, post-infection PZQ treatment showed fewer and significantly smaller granulomas than post-infection WJMSCs treatment. Nevertheless, post-infection WJMSCs exhibited non-significant less TGFB-stained fibrogenesis. CONCLUSION: CD34+UCBSCs exerted the best prophylactic and therapeutic roles in prevention and complete cure of acute hepatic S.mansoni granulomas over WJMSCs and PZQ. In contrast, only pre-infection WJMSCs exhibited similar preventive (prophylactic) effect. On the contrary, post-infection WJMSCs were the worst (incompletely reversed granulomas). Post-infection Praziquantel was overall better therapeutically than WJMSCs in this regard. Accordingly, when it comes to WJMSCs application, WJMSCs are better used as a pre-infection prophylactic and preventive tool rather than a post-infection therapy. Further studies are needed.