The prophylactic and curative effect of oltipraz in experimental schistosomiasis mansoni in mice.

Effect of oltipraz on immature and mature forms of Schistosoma mansoni in mice experimentally infected with the Egyptian strain of the worms was assessed. The drug was administered to different groups of mice in a single oral dose of 750 mg/kg body weight 2 hours before infection, 7 days and 15 days after infection and in a single oral dose of 500 mg/kg body weight 30 days and 45 days after infection. Oltipraz was found to be active in reducing the number of worms significantly only when administered in a higher dosage 2 hours before infection and 7 days after infection. Thereafter, the parasites were refractory to the drug action until they have reached sexual maturity 45 days post-infection.

Oltipraz treatment in experimental schistosomiasis mansoni:VII. Effect of high dose oral therapy on alkaline phosphatase level in livers of infected mice.

Biochemical estimation of alkaline phosphatase (AP) in livers of mice experimentally infected with the Egyptian strain of S. mansoni before and after oltipraz treatment was carried out. The drug was given in a single oral dose of 500 mg/kg body weight. The results revealed that the drug led to gradual reduction in the AP mean level after 20 and 30 days from treatment. This was then followed by rise in the enzyme mean level, after 60 days. The drug also caused significant reduction in the AP mean level in livers of the drug control group of mice after 5 and 20 days from oltipraz administration in comparison normal uninfected controls. These findings might be attributed to a hepatocytotoxic effect of the drug.

Oltipraz treatment in experimental schistosomiasis mansoni: IV. Histopathological changes in the intestines of infected mice induced by high dose oral therapy.

Marked improvement of the pathological lesions in the small intestines of mice experimentally infected with the Egyptian strain of S. mansoni was detected after oltipraz therapy. The drug was given in a single oral dose of 500 mg per kg body weight. The improvement of the intestinal lesions was apparent after 20, 30 and 60 days from treatment in comparison to the infected untreated controls. These findings were the basis of the present study, which still need investigations of the histopathological changes in livers of infected mice before and after oltipraz therapy.

Oltipraz treatment in experimental schistosomiasis mansoni: V. Histopathological changes in the livers of infected mice induced by high dose oral therapy.

Histopathological changes in the livers of mice infected with the Egyptian strain of S. mansoni before and after oltipraz therapy were studied. The drug was given in a single oral dose of 500 mg/kg. body weight. The results obtained revealed marked improvement of the pathological lesions after 20 and 30 days from oltipraz therapy in comparison to the infected untreated controls. That improvement was followed by a marked increase of hepatic lesions after 60 days from treatment in addition to new cellular granulomata surrounding fresh bilharzial ova. The drug was severely toxic to the liver as it caused severe liver cell injury, parenchymatous inflammation, fatty changes and areas of diffuse necrosis in livers of the drug control group of mice, the results were discussed in the light of the previous and present findings detected by the authors, with some recommendations.

Oltipraz treatment in experimental schistosomiasis mansoni: VI. Effect of high dose oral therapy on alkaline phosphatase level in the intestines of infected mice.

Extraction of alkaline phosphatase (AP) from the tissues of small intestines of mice experimentally infected with the Egyptian strain of S. mansoni before and after oltipraz treatment was carried out. The drug was given in a single oral dose of 500 mg/kg body weight. The results obtained revealed that the drug led to significant reduction in the AP mean level after 30 and 60 days from therapy in comparison to the infected untreated controls. Oltipraz also caused significant reduction in the intestinal AP mean level of the drug control group of mice after 5 and 20 days from drug administration in comparison to normal controls, which might be attributed to the toxic effect of the drug on the intestinal cells.

Oltipraz treatment in experimental schistosomiasis mansoni. II. Effect of high dose oral therapy on worm load and process of copulation in infected mice.

A single oral dose of 500 mg/kg body weight of Oltipraz was given to mice experimentally infected with the Egyptian strain of S. mansoni. The drug caused significant reduction in the number of worms and marked reduction in the percentage of paired worms in comparison to the infected untreated controls. This reduction in number was apparent after 5 days, 7 days and 2 days from Oltipraz administration, then the number gradually increased with elapsed time till the 60th day after therapy (the end of the work). The previous findings might indicate development of resistance to Oltipraz among the Egyptian strain of S. mansoni worms with prolongation the period of worms exposure to the drug.

Oltipraz treatment in experimental schistosomiasis mansoni: III. Effect of high dose oral therapy on hepatic shift of worms and tissue bound ova pattern in infected mice.

Oltipraz was given in a single oral dose of 500 mg per kg body weight to mice experimentally infected with the Egyptian strain of S. mansoni. The drug caused marked hepatic shift of the worms in comparison to the infected untreated controls. Hepatic shift of worms was apparent till the 30th. day from oltipraz administration, while pronounced back shift to mesenteric veins by the surviving parasites occurred 60 days post-treatment. The drug also caused death of all bilharzial eggs located inside tissues of the small intestines of infected mice and complete eradication of faecal eggs after the 5th., 7th., 20th., 30th. and 60th. days from therapy. These findings are in need of histopathological investigations.

Oltipraz treatment in experimental schistosomiasis mansoni. I. Morphological changes among S. mansoni worms induced by high dose oral therapy in mice.

Worms recovered from Oltiparz treated group of mice (500 mg/kg. body weight) show, suntedness, absent or poorly developed tuberculations, destroyed or poorly developed suckers, absence or severe atrophy of testes, complete absence or severe atrophy of ovaries, small or empty vitelline follicles and slightly or not pigmented intestines as compared with controls; the female worms are more affected than males. The morphological changes are apparent after 5 days, 7 days, 20 days and 30 days from drug administration, but are reversible in some surviving worms especially male worms after 60 days from therapy. The previous findings indicate that the drug causes severe degenerative changes in the structure of both S. mansoni male and female worms and that resistance to the drug develops among the Egyptian strain of S. mansoni worms with prolongation the period of worms exposure to the drug. The present results are discussed with those of others with some recommendations.

Effect of urinary bilharzial infection on male pubertal development and endocrine functions.

One hundred seventy-five males aged 9-20 years were selected. The subjects comprised two groups; controls and patients infected with urinary bilharziasis not associated with any other parasite. Pubertal development was assessed. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and progesterone were determined by radioimmunoassay procedure. Delay in pubertal development was evident in the normal control group as indicated by higher chronological age mean values at the various stages as compared to other world norms. Urinary bilharziasis exaggerated the delay in pubertal development as compared to that in the control group. In relation to the control group, the group with urinary bilharziasis had higher levels of serum FSH and LH, which were significant only at stages III and IV. No significant difference was noted between the two groups for serum testosterone and progesterone levels, except for the high progesterone mean value at stage V in the group with urinary bilharziasis.