ABSTRACT
The effects of theophylline, diltiazem, deferoxamine and minoxidil with and without praziquantel [PZQ] were tested on Schistosoma mansoni infected mice to investigate their possible effect on the progression of hepatic granulomatous reaction into fibrosis in murine schistosomiasis. 66 male Swiss strain albino mice were used in the study. They were divided into 4 groups; control group; infected and treated with PZQ [1000 mg/kg/day] orally for two successive days; infected and treated for 2weeks with deferoxamine [25 mg/kg/day], diltiazem [24 mg/kg/day], theophylline [30 mg/kg/day], or minoxidil [1.0 mg/kg/day]; infected and treated with each of the previous drugs combined with PZQ. At the 10[th] week postinfection, animals were subjected to splenic pulp pressure measurement. The pathological changes in the liver were examined by routine H and E and Masson Trichrome stains. Livers were examined for egg count, granulomas number and size. Liver collagen deposition was also determined. Statistical correlation of the results was done. Praziquantel significantly reduced liver egg count, granulomas number and size. It decreased liver fibrosis assessed histopathologically, liver collagen content and portal venous pressure but not to significant levels. None of the tested drugs [deferoxamine, theophylline, diltiazem, or minoxidil] succeeded to reduce schistosoma egg deposition or granulomas number and size in livers of schistosoma-infected mice. However, significant reduction in these parameters was achieved only when PZQ was added to the treatment regimen. Deferoxamine, theophylline, and minoxidil significantly decreased level of hepatic fibrosis, collagen deposition and portal venous pressure. These effects were significantly augmented when PZQ was combined with any of these drugs. Diltiazem alone or in combination with PZQ failed to decrease liver collagen content or hepatic fibrosis induced by schistosoma infection. However, diltiazem alone or in combination with PZQ could significantly reduce portal venous pressure. Accordingly, it is recommended to extend this animal study to human to investigate the possible mitigation of the deleterious effects of schistosomiasis on the liver by the addition of deferoxamine, theophylline, or minoxidil to its treatment regimen. Diltiazem can also be used to reduce portal venous pressure