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Abstract Background Praziquantel (PZQ) is an isoquinoline derivative (2-cyclohexylcarbonyl-1, 2, 3, 6, 7, 11b-hexahydro-4H-pyrazino{2,1-a}-isoquinoline-4-one), and is currently the drug of choice for all forms of schistosomiasis. Silymarin, a standardized milk thistle extract, of which silibinin is the main component, is known for its hepatoprotective, anti-inflammatory, antioxidant activities, and hepatocyte regeneration. This study investigates the anti-inflammatory/anti-fibrotic effects of silymarin and/or PZQ on schistosomal hepatic fibrosis. Methods Schistosoma mansoni-infected mice were divided into two large groups (I & II), each with four subgroups and were run in parallel. (i) Infected untreated; (ii) treated with silymarin, starting from the 4th (3 weeks before PZQ therapy) or 12th (5 weeks after PZQ therapy) weeks post infection (PI); (iii) treated with PZQ in the 7th week PI; and (iv) treated with silymarin, as group (ii) plus PZQ as group (iii). Comparable groups of uninfected mice run in parallel with the infected groups. Mice of groups I and II were killed 10 and 18 weeks PI, respectively. Hepatic content of hydroxyproline (HYP), serum levels and tissue expression of matrix metalloproteinase-2 (MMP-2), transforming growth factor-β1 (TGF-β1) and number of mast cells were determined. In addition, parasitological, biochemical and histological parameters that reflect disease severity and morbidity were examined. Results Silymarin caused a partial decrease in worm burden; hepatic tissue egg load, with an increase in percentage of dead eggs; modulation of granuloma size, with significant reduction of hepatic HYP content; tissue expression of MMP-2, TGF-β1; number of mast cells, with conservation of hepatic reduced glutathione (GSH). PZQ produced complete eradication of worms, eggs and alleviated liver inflammation and fibrosis. The best results were obtained, in most parameters studied, in groups of mice treated with silymarin in addition to PZQ. Conclusions Our results point to silymarin as a promising anti-inflammatory and anti-fibrotic agent; it could be introduced as a therapeutic tool with PZQ in the treatment of schistosomal liver fibrosis, but further studies on mechanisms of silymarin and PZQ in chronic liver diseases may shed light on developing therapeutic methods in clinical practice.

Non-alcoholic fatty liver disease (NAFLD) is a burgeoning health problem that affects 1/3 of the adult population and an increasing number of children in developed countries. Oxidative stress and insulin resistance are the mechanisms that seem to be mostly involved in its pathogenesis. This study was conceived in a NAFLD rat model to evaluate the efficacy of both metformin (MTF) and N-acetylcysteine (NAC) with dietary control on biochemical and histologic liver manifestations. Rats were classified into nine groups; normal (I), NAFLD-induced by feeding high-fat diet (HFD; II) for 12 weeks, NAFLD switched to regular diet (RD; III), NAFLD-HFD or -RD treated with MTF in a dose of 150 mg/kg (IV, V), NAC in a dose of 500 mg/kg (VI, VII) or MTF+NAC (VIII, IX) respectively for 8 weeks. After 20 weeks, the rats in group II showed notable steatosis, lobular inflammation, fibrosis accompanied with elevated ( P < 0.05) serum alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (γ-GT), cholesterol, triglycerides, LDL, VLDL, leptin, tumor necrosis factor (TNF-α), transforming growth factor (TGF-β1) and hepatic malondialdehyde (MDA) compared with group I. Meanwhile, hepatic superoxide dismutase (SOD), glutathione GSH with serum HDL, adiponectin were significantly decreased ( P < 0.05). These changes were to a less extent in group III. MTF or NAC individually resulted in improvement of most of these biochemical and histological parameters. These improvements were more pronounced in the combined groups VIII and IX versus each drug alone. NAC supplementation concomitant with MTF could be beneficial for the treatment of NAFLD and prevention of nonalcoholic steatohepatitis (NASH).

The prevalence of non-alcoholic fatty liver disease (NAFLD) has markedly increased, especially in patients exhibit one or more features of the metabolic syndrome. This study investigates the effect of rosuvastatin (RSV) and/or β-carotene (βC) in NAFLD-induced rats. Rats were classified into nine groups; normal (I), NAFLD-induced with high-fat diet (HFD; II), NAFLD switched to regular diet (RD; III), NAFLD-HFD or NAFLD-RD treated with RSV (IV, V), βC (VI, VII) or both RSV+βC (VIII, IX), respectively. After four weeks, rats were sacrificed to obtain serum samples and liver tissues. Liver histology, lipid profile, liver oxidative stress markers, and adipocytokines were measured. Liver sections of rats with NAFLD-HFD revealed steatosis, lose of hepatic architecture, inflammation and hepatocyte vacuolation with high percentage of cell fibrosis. Serum levels of ALT, AST, ALP, gamma glutamyl transferase (GGT) and lipid profile (triglycerides, cholesterol, LDL and VLDL) were significantly increased (P<0.05) compared with normal. Also, hepatic malondialdehyde level and serum leptin, tumor necrosis factor-alpha (TNF-α) and transforming growth factor-β1 (TGF-β1) were increased. Meanwhile, superoxide dismutase (SOD) activity, GSH content in liver, serum HDL and adiponectin were decreased (P<0.05) vs normal. These changes were observed to a lesser extent in NAFLD-RD group. Administration of RSV or/and βC almost improved all previously mentioned parameters. Moreover, hepatic steatosis was decreased and inflammation was markedly ameliorated with reduction of TNF-α and TGF-β. These results were more pronounced in the groups VIII and IX vs each drug alone. In conclusion RSV and βC could be beneficial for the treatment and prevention of NAFLD. Combined RSV with βC is more effective than RSV alone.

Non-alcoholic fatty liver disease (NAFLD) includes a broad spectrum of fat-induced liver injury, ranging from mild steatosis to cirrhosis and liver failure. This study investigates the hepatoprotective properties of garlic and onion in NAFLD rat model. Ninety male Sprague-Dawley rats were randomly divided into 9 groups; normal (I), NAFLD induced with high fat diet (HFD; II), NAFLD switched to regular diet (RD; III), NAFLD-HFD or NAFLD-RD treated with garlic (IV, V), onion (VI, VII) or the combined garlic+onion (VIII, IX) respectively. A NAFLD rat model was established by feeding the animals with a high-fat diet for 12 wk. These animals were then treated with garlic or/and onion or vehicle for 8 wk (weeks 13-20) and then killed to obtain serum samples and liver tissues. Liver histology, lipids, parameters of oxidative stress, TNF-α and TGF-β were measured. The liver in NAFLD-HFD showed typical steatosis, accompanied with mild to moderate lobular inflammatory cell infiltration. Serum levels of ALT, AST, ALP, leptin, cholesterol, triglycerides, TNF-α, TGF-β and hepatic MDA' were significantly increased (P < 0.05) compared with normal group. This was accompanied with reduction of hepatic GSH, GR, GPx, GST, SOD and serum adiponectin. These changes were to a less degree in NAFLD-RD group. Combined administration of garlic+onion produced a better and significant decrease in liver steatosis, serum liver enzymes, oxidative markers and lipid peroxidation versus each one alone. In the same time, NAFLD-induced inflammation was also mitigated via reduction of TNF-α and TGF-β. In addition, these results were better in the group IX versus group VIII.

Unlabelled: Artemether (Art), a derivative of the antimalarial artemisinin, also exhibit antischistosomal properties. N-acetylcysteine (NAC) has a diversity of applications, largely because of the chemical properties of the thiol moiety present in its structure. The ability of this moiety to sweep reactive oxygen species is well-established with NAC. This study investigates the ability of NAC to enhance the therapeutic potential of Art against adult Schistosoma mansoni infection and evaluates the protective role of this antioxidant on S. mansoni-induced oxidative stress. Mice were divided into five groups; normal (i), infected control (ii), infected treated with NAC, 300mg/kg 5 days a week/4weeks (iii), infected treated with Art (300mg/kg) 7 weeks post infection (iv) and infected treated with both NAC and Art (v). Results showed that Art produced a significant reduction in total number of worms when used alone. Also, it decreased hepatic ova count significantly accompanied with an increase in the percentage of dead ova. Treatment with NAC alone increased the percentage of dead ova; meanwhile, it enhanced the decrease in total number of worms and hepatic ova count when used with Art. Infection with S. mansoni significantly increased tissue GSH, GR, SOD and serum ALT and GGT, while decreased the activities of GST, GPx and the levels of proteins and albumin compared to normal control. Treatment with NAC alone approximately recovered the contents of GSH, activities of GPx and levels of serum albumin, ALT and GGT relative to normal control. A tendency for normalization in activities of the antioxidant enzymes mentioned above and serum levels of liver function tests was observed in the groups treated with Art alone or Art+NAC., Conclusion: NAC downregulates oxidative stress induced by S. mansoni infection and enhances the therapeutic potential of artemether against adult schistosomes., (Copyright © 2011 Elsevier Inc. All rights reserved.)

In a recent study, the fasciolicidal activity of Mirazid (a myrrh-derived drug) and its effect on the function and histopathology of host liver were investigated in Egyptian sheep, with triclabendazole (TCBZ) used as the positive control. Sheep were infected with metacercariae (150/animal) and treated 3 months later, either with Mirazid (10 mg/kg/day for six consecutive days) or TCBZ (a single dose of 10 mg/kg), or left untreated, as controls. When the animals were killed 4 weeks after the end of treatment, no Fasciola flukes or eggs could be found in the animals given TCBZ but the number of flukes found in the Mirazid-treated animals was only 6% lower than that recorded in the untreated sheep (a statistically insignificant difference). In terms of their Fasciola egg loads, serum concentrations of hepatic enzymes and hepatic histopathological changes, the Mirazid-treated sheep appeared very similar to the untreated, infected animals. The TCBZ-treated animals, in contrast, showed remarkably little evidence of hepatic pathology. It therefore appears that, in the treatment of ovine fascioliasis, at least some batches of Mirazid have little, if any, value.

This study investigates the development of the Egyptian strain of Schistosoma haematobium and the resultant immunohistopathology and biochemical changes in organs affected. In addition, the response of different developmental stages of S. haematobium worms to praziquantel (PZQ) was examined. Schistosoma haematobium-infected hamsters were classified into 4 groups and were treated at day 35, 55, 75, and 95 postinfection (PI), respectively. Each group was subdivided into 3 subgroups. Two of them were treated orally with PZQ (300 mg/kg or 500 mg/kg divided equally on 2 consecutive days), and the third group was left without treatment. Treated groups were killed 20 days posttreatment. Infection with S. haematobium became patent 73 days PI; tissue egg load and worm fecundity were higher at 95 days and maximal 115 days PI, with an oogram pattern comparable to that in Schistosoma mansoni infection. In the liver, small cellular granulomas were observed 75 days PI, with preponderance of CD4+ T-cell phenotypes. In the urinary bladder, only submucosal focal Brunn's-nest formation and angiogenesis without typical granulomas were observed. Ninety-five and 115 days PI, confluent granulomata with multiple eggs in the center were observed in the liver and urinary bladder, with a preponderance of CD8+ positive T cells in the liver and hyperplasia of the urinary bladder epithelium with cystitis cystica and papillae formation. One hundred percent worm eradication was recorded with the higher dose of PZQ in animals treated 75 and 95 days PI. In conclusion, in spite of the long prepatent period of the Egyptian strain of S. haematobium, sensitivity to PZQ was recorded soon after infection. Granulomata were similar to those of S. mansoni in the livers and urinary bladders, but they were confluent with multiple eggs in the centers, hyperplasia of the urinary bladder urothelium with cystitis cystica, papillae, and Brunn's-nest formation predictive of malignant changes with no hepatocyte dysplasia.

The level of drug-metabolizing enzymes (cytochrome P450 [CYP450] and cytochrome b5 [cyt b5]) and the bioavailability of praziquantel (PZQ) were investigated in batches of mice infected with Schistosoma mansoni displaying either a decreased susceptibility to PZQ ("EE2" and "BANL"-isolates), or a normal susceptibility to the drug ("CD" isolate). Each batch was divided into 2 groups. The first group was further subdivided into 5 subgroups. Subgroups 1 to 4 were treated 7 wk postinfection (PI) with oral PZQ at 25, 50, 100, and 200 mg/kg for 5 consecutive days, whereas the fifth subgroup was administered the vehicle only as control. Animals were perfused 9 wk PI, and worms were counted to estimate PZQ ED50. CYP450 and cyt b5 were examined in hepatic microsomes of infected untreated mice and of infected mice treated with 25 and 200 mg/ kg PZQ. The second group was given PZQ 7 wk PI and was further subdivided into 11 subgroups, killed at 2, 5, 15, 30, 60, 90, 120, 150, 180, 240, and 360 min postdosing to study pharmacokinetic parameters of PZQ. Mice harboring S. mansoni isolates having higher PZQ ED50 (170.3 mg/kg for EE2 and 249.9 mg/kg for BANL vs. 82.96 mg/kg for CD) had higher levels of CYP450 and cyt b5, a PZQ Cmax decreased by 19-30% and area under the serum concentration-time curve0-6 hr decreased by 57-74%. Data suggest that S. mansoni isolates that are less sensitive to PZQ induce a lower inhibition of hepatic drug-metabolizing enzymes, with a consequently higher metabolic transformation of PZQ.

Artemether is an efficacious antimalarial drug that also displays antischistosomal properties. Grapefruit juice increases the oral availability of a variety of the CYP3A4 substrates. This study was designed to evaluate the effect of repeated administration of grapefruit juice with artemether on the hepatic activities of cytochrome P-450 (CYP450) and cytochrome b5 (cyt b5), on the serum levels of some biochemical enzymes and antischistosome efficacy. Results showed that administration of grapefruit juice alone induced more inhibition in the hepatic activities of CYP450 and cyt b5 than that produced by Schistosoma mansoni infection. Moreover, it enhanced degeneration of eggs and accelerated healing of the pathological granulomatous lesions. Treatment of S. mansoni-infected mice with artemether at a total dose of 300 mg/kg resulted in total and female worm burden reductions of 66.7 and 90.1%, respectively, hence protecting the host from damage induced by schistosome eggs. Treatment of S. mansoni-infected mice with artemether at 150 mg/kg reduced the total and female worm numbers by 43.3 and 54.4%, respectively, thus somewhat ameliorating hepatic granulomatous lesions compared with the infected untreated group. This was associated with no change in the hepatic activities of CYP450 and cyt b5 and in the serum levels of total protein, albumin, globulin and alanine aminotransferase compared with the uninfected control group. Coadministration of grapefruit juice with the lower dose (150 mg/kg) of artemether eliminated eggs and granulomatous reactions. In this group, the inhibitory effects of grapefruit juice on CYP450 and cyt b5 were apparent but serum liver enzymes were unchanged compared with the uninfected control group. Coadministration of grapefruit juice with artemether achieved complete protection of the host from damage induced by schistosomal infection.

One of the most commonly used drugs for clinical management of schistosomiasis is praziquantel (PZQ, CAS 55268-74-1). Now, PZQ is recognized, world wide, as a powerful therapeutic agent for the control of schistosomiasis. Previous studies have shown decreased activities of some of the microsomal drug-metabolizing enzymes in the livers of S. mansoni-infected mice. Consequently, this work was initiated in order to investigate the effect of PZQ treatment (in a total dose of 1000 mg/kg given on two consecutive days each of 500 mg/kg body weight) administered to mice with or without previous S. mansoni infection on selected liver microsomal drug-metabolizing enzymes. The effect of these factors on liver function was also studied. The drug was given orally seven weeks after infection with 80 Egyptian strains of S. mansoni cercariae/mouse. The activities of aminopyrine-N-demethylase, aniline hydroxylase and the hepatic glutathione content as well as the concentrations of gamma-glutamyl transferase were measured after different time intervals following the second dose of PZQ treatment. The results indicated a meaningful decrease in the activities of aminopyrine-N-demethylase and aniline hydroxylase and a high elevation in the concentrations of gamma-glutamyl transferase and the contents of hepatocellular glutathione in mice infected with S. mansoni compared with their corresponding control groups. After two weeks following the praziquantel treatment, there was an improvement in the activities of these enzymes towards the control values. Collectively, the present findings point to the importance of initiating more studies in this discipline and careful deliberation of results in order to fully understand the possible interactions of antibilharzial drugs with the liver microsomal drug-metabolizing enzymes.

The effect of Schistosoma mansoni infection on drug-metabolizing enzymes was investigated before and after treatment of S. mansoni-infected male albino mice with the antibilharzial drug praziquantel (CAS 55268-74-1). The drug was given in a total dose of 1000 mg/kg, and was administered at 500 mg/kg of body weight for two consecutive days each of 500 mg/kg of body weight. The drug was given 49 days after infection with 80 Egyptian strains of S. mansoni cercariae/mouse. The hepatic content of cytochrome P-450, cytochrome b-5 and NADPH cytochrome P-450 reductase were determined at 4, 8, 24, 72 h, one and two weeks after the second dose of treatment. The enzymes were determined in the microsomal fraction after homogenization and ultracentrifugation at 105,000 x g. The results indicate a marked decrease of most enzymes in the infected groups compared to normal controls. Two weeks after treatment there was an improvement of the level of most enzymes towards the normal values. The levels of liver function tests were also improved. Concerning the oogram pattern, there was a rapid change even after 8 h after the second dose of treatment. It was concluded that the antibilharzial drug could be considered as a safe drug with a rapid onset of action.

Colchicine in a dose of 200 micrograms kg body weight/day (5 days/week) was administered to groups of Schistosoma mansoni infected mice 12 weeks post infection, either alone or following previous praziquantel therapy at the 8th week of infection. Certain groups received colchicine for 6 weeks and others received it for 10 weeks. Colchicine alone did not significantly change the light microscopic appearance of schistosomal liver fibrosis, or hepatic collagen content estimated histomorphometrically, and did not reduce the elevated IL-2 serum level. Colchicine induced hepatic injury consisted of intense inflammatory reaction in granuloma and portal tracts, hepatocytic degeneration, and elevation of serum AST and ALT levels. Colchicine seemed to postpone granulomatous reaction healing and collagen deposition rather than inhibiting collagen formation or degrading it. Colchicine inhibited proliferation of hepatocytes of infected mice by expanding G2-M phases of cell cycle, thus reduced Ag NOR count and raised cell ploidy and cyclic AMP serum level. Subsidence of schistosomal infection by praziquantel prior to colchicine therapy greatly reduced inflammatory cellular reaction, significantly diminished hepatic collagen deposition and serum IL-2 level, minimized the elevated nuclear ploidy and cyclic AMP serum level that followed colchicine therapy when administered alone.

Colchicine alone or following praziquantel was given to mice infected with Schistosoma mansoni either 6 or 10 weeks post infection. Praziquantel increased body weight gain, histologically reduced number, diameter and cellularity of granuloma and improved liver function parameters. Early praziquantel therapy decreased hepatic collagen content as detected by the colorimetric method and the serum procollagen propeptide (PIIIP), while later treatment at the 10th week of infection increased hepatic collagen content and serum PIIIP. Colchicine therapy significantly decreased body weight gain with significant weight loss after early treatment. Colchicine did not change the histologic picture of schistosomal liver fibrosis; it induced a detectable hepatocytic injury recorded ultrastructurally and histologically with excitation of the inflammatory reaction in the granuloma and in portal tracts after early treatment. Excess pigmentation in macrophages and Kupffer cells, binucleation and large sized hepatocytic nuclei were evident after colchicine therapy. Colchicine increased hepatic collagen content microgram/mg protein, raised globulin and total serum protein and normalized the raised serum PIIIP of infected mice, but had no effect on PIIIP of normal mice. Early cessation of schistosomal infection evidently minimized the adverse effects of colchicine.

This study aimed to test the therapeutic effect of two antischistosomal drugs metrifonate (CAS 52-68-6) and praziquantel (CAS 55268-74-1), either alone or in combination, on mice infected with schistosoma mansoni. Both drugs were given in half of their therapeutic doses 8 weeks post infection. Animals were sacrificed two weeks after the last dose. The efficacy of the drugs was evaluated using the number of ova/g tissue, the distribution and the number of Schistosoma worms. Praziquantel and metrifonate alone produced about 91% and 22% reduction in total worm burden. The reduction in ova count in intestine and liver was 96% and 85%, respectively, using praziquantel alone while it was only 6 and 12%, respectively, after metrifonate treatment. After treatment with both drugs given in combination the number of ova count was not changed as compared with praziquantel alone; also there was no change in the worm load as compared with praziquantel. It is concluded that a combination of a low dose of praziquantel with metrifonate failed to produce any significantly better effect.

In this work, praziquantel (EMBAY 8440, CAS 55268-74-1), an oral antihelminthic drug effective against the three species of schistosomes pathogenic to man, was tested alone and in combination with cimetidine (CAS 51481-61-9), aH2-receptor antagonist having a known potentiative power when combined with other drugs. Both drugs were tested in different doses and regimen either alone or in combination by giving them to S. mansoni infected Swiss albino mice (100 cercariae/mouse) 7 weeks post infection. Cimetidine was tested in doses of 50, 100 and 200 mg/kg for 2 consecutive days; praziquantel was given in doses of 100 and 500 mg/kg for 2 consecutive days. It was found that the best regimen was that of cimetidine and praziquantel when given simultaneously. Both drugs when given in a dose of 100 mg/kg for 2 consecutive days reduced the total worm load by 84.61%, while a percent reduction of 75.1% and 88.9% was recorded in hepatic and intestinal tissue egg load, respectively. Maximum efficacy was recorded when both drugs were given simultaneously at 200 mg/kg for 2 consecutive days. This regimen completely eradicated all schistosome worms and resulted in the maximum reduction in total tissue egg load (92%). The efficacy of this regimen was nearly the same as that of the full dose of praziquantel (500 mg/kg for 2 consecutive days), gave 100% worm eradication and 95% reduction in total tissue egg load.

The elevated levels of lipid peroxide product as malondialdehyde (MDA) in plasma, liver, spleen, intestine and kidney of Schistosome-infected mice were differently ameliorated by treatment with praziquantel (EMBAY 8440, CAS 55268-74-1) (2 x 500 mg/kg body wt.) being nearly normalized in plasma and intestine, moderately improved in liver and slightly affected in spleen and kidney. However, the drug failed to affect the MDA levels in the different organs of healthy mice. Moreover, the increased hepatic superoxide dismutase (SOD) activity in infected mice was normalized while the decreased activities in the other tissues were further decreased than normal values in response to praziquantel treatment. Interestingly, in healthy mice, the drug similarly inhibited SOD activities in blood, spleen and kidney. The specificity of this action remains to be clarified. Possible explanations of these findings are given.

The schistosomicidal efficacy of praziquantel (2 x 500 mg/kg), oxamniquine (1 x 100 mg/kg) and combined one-third the curative dose of each of them (333 mg/kg praziquantel + 33 mg/kg oxamniquine), were correlated to gonadal steroid hormonal changes and state of disease immunopathology, in mice infected with 100 Schistosoma mansoni (S. mansoni) cercariae. Maximum efficacy recorded with combination regimen particularly 4 weeks after treatment, was accompanied by maximum reduction in granuloma volume (65%), least fall in testosterone level (-56.2 and -60.2% in male and female mice respectively) and increased progesterone level (+33.9 and +81.5% in male and female mice respectively). These findings revealed a potentiated effect of combination therapy on mature infection and the possible involvement of gonadal steroid hormones in affecting the efficacy of schistosomicidal drugs and state of disease immunopathology.

The disposition phenazone (antipyrine) was used to study the effect of Schistosoma mansoni infection on the activity of drug metabolizing enzymes in mice. Plasma elimination rate constant (Ke), elimination half-life (t1/2e), clearance (CL) and apparent volume of distribution (Vd) were estimated 8 and 12 weeks after infection of mice with 80 S. mansoni cercariae. Liver and kidney function tests were performed simultaneously. Infection increased the levels of glutamic oxalacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), lactic dehydrogenase (LDH), alkaline phosphatase (AP) and total proteins 8 and 12 weeks post infection. At the same time a decrease was recorded in the total cholesterol level. Moreover infection with S. mansoni produced a decrease in phenazone clearance with an increase in the area under the curve (AUC) of the drug 8 and 12 weeks post infection. Elimination half-lives were 57.92 +/- 14.10 and 72.72 +/- 4.14 min 8 and 12 weeks after infection, respectively, compared to 19.29 +/- 3.30 and 26.14 +/- 5.31 min in corresponding controls. No statistically significant change was recorded in the volume of distribution of phenazone in the groups studied. In addition no significant correlation was found between parameters of phenazone disposition and the enzyme levels studied 8 and 12 weeks after infection.

The activities of GOT and GPT in the hemolymph of B. alexandrina were significantly decreased by S. mansoni infection. However, the total protein concentration and AcP activity were increased. Although the snail starvation decreased AcP activity in the ovotestis, it increased GOT activity in the other organs of the snails. On the other hand, the snail feeding after starvation increased significantly AcP activity in ovotestis. Natural and synthetic molluscicides inhibited the activities of GOT and GPT, however, they increased the total protein concentrations and AcP activities in the examined organs.

Schistosoma mansoni infection in mice resulted in a marked decrease in blood glucose and liver glycogen accompanied by a significant increase in hepatic glucose-6-phosphatase (G-6-Pase) activity. Moreover, the results indicated that infection produced a significant increase in blood pyruvate and hepatic glucose-6-phosphate dehydrogenase (G-6-PD) activity with a significant decrease in blood lactate. Infected mice were treated with praziquantel which was given at two doses of 500 mg/kg body wt on two consecutive days. Seven and 14 days respectively after drug administration, such treatment caused a marked improvement in the previous aspects of carbohydrate metabolism. This is indicated by the tendency of the blood glucose of infected mice to be restored, the marked increase in their liver glycogen content, the normalization of their blood lactate and pyruvate as well as by the marked decrease of their hepatic G-6-Pase activity and the progressive increase in their hepatic G-6-PD activity. Praziquantel given to normal mice moderately affected the blood glucose and the previously mentioned hepatic enzymes. However, the drug markedly increased the liver glycogen content of normal mice and failed to elicit any change in their blood pyruvate and lactate. Possible explanations of these findings are discussed.