RESUMO
Blastocystis hominis is a cosmopolitan protozoan that has been associated with several gastrointestinal disturbances involving lactose intolerance. However, the underlying pathogenic factors remain indistinct. 20 Swiss albino mice were utilized and assembled into four groups, each of five mice: group-I: received neither infection nor lactose (healthy control), group-II: received a single dose of 10,000 cysts of Blastocystis and lactose diets in a dose of 12.5 g/day/mouse for 7 consecutive days starting from day 14 p.i., group-III: non-infected mice with oral doses of lactose (12.5 g/day/mouse) for 7 consecutive days (positive control), group-IV: infected mice on lactose free diet (negative control). We investigated the histopathological changes using H&E stain.s Also, lactase enzyme activity was measured using spectrophotometry and the production of TNF-α and apoptotic events were explored via immunohistochemistry and compared in the small intestine of all groups. The active inflammatory changes in the infected animals were moderate in the form of loss of villous architecture, increased ILC (P-value > 0.001) besides scattered forms of the parasite as compared to non-infected mice. There was a reduction in lactase enzyme activity p.i. The TNF-α levels were induced p.i. as compared to non-infected mice (P-value > 0.001). The expression of Bax protein was upgraded, while Bcl-2 expression decreased significantly with a reverse in Bax/Bcl2 ratio in infected animals. Blastocystis infection appears to humble lactase enzyme activity via the induction of apoptosis in the epithelial cells of the small intestinal brush border in a TNF-α associative pathway.
RESUMO
Schistosomiasis mansoni is considered one of the most common fibrotic diseases resulting from inflammation and deposition of fibrous tissue around parasitic eggs trapped in the liver, causing morbidity and mortality. Chemotherapy against schistosomiasis is largely dependent on Praziquantel (PZQ). Yet, the huge administration of it in endemic areas and its incompetence towards the immature stages have raised serious alarms against the development of drug resistance. Few drugs are directed to reverse schistosomal liver fibrosis, particularly at the chronic and advanced stages of the disease. Recently, protein tyrosine kinase (PTK) inhibitors have been identified as potent anti-schistosomal and anti-fibrotic drugs against schistosomes, that may suppress and reverse Schistosoma mansoni (S. mansoni) induced liver fibrosis. The present study was designed to assess the anti-schistosomal and antifibrotic activity of Genistein, a PTK inhibitor, in comparison to PZQ, on both acute and chronic S. mansoni-infected mice using different parasitological, histopathological and immunohistochemical studies. Genistein showed a significant reduction (Pâ¯<â¯.05) in total worm burden, tissue egg load, mean hepatic granulomas diameter and numbers, percentage of collagen and expression of transforming growth factor-beta 1 (TGF-ß 1) in the examined hepatocytes with elevation in percentage of degenerated ova, in comparison to the control groups, in both acute and chronic stages of infection. The best results were obtained when Genistein was combined with PZQ. Therefore, it was concluded that Genistein showed a promising anti-schistosomal and anti-fibrotic properties which could make it one of the new potential targets in chemotherapy against schistosomiasis.