Effect of praziquantel treatment on the activities of some liver microsomal enzymes in mice infected with Schistosoma mansoni.

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.

Effect of Schistosoma mansoni infection and treatment on 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.

Effects of three fractions obtained from Naja haje venom on hemolysis and lipid metabolism in rabbits

Three fractions (F1, F2 and F3) were obtained from the venom of the Egyptian cobra Naja haje by gel filtration. F1 and F2 had indirect hemolytic effects on rabbit erytrocytes. The HU50 (the amount of the fraction causing 50 per cent hemolysis) values of F1 and F2 were 12.04 ñ 3.89 and 36.57 ñ 2.20 ug, respectively. The effects of the three cobra venom fractions on lipid metabolism were studied after 1, 2 3 and 4 hours. Serum total lipids and cholesterol were significantly decreased at almost all tested times, but variable changes were observed in the serum triglycerides. Serum inorganic phosphorus levels were significantly increased with F1 and F2 administration more than that with the F3 fraction. These results suggest that F1 and F2 possess phospholipase A2-like activities and their effects on the lipid metabolism is more intense than that of F3.

Hormonal and histological effects of chronic caffeine administration on the pituitary-gonadal and pituitary-adrenocortical axes in male rabbits.

Daily administration of caffeine (30 or 60 mg/kg) to mature male rabbits for four consecutive weeks caused an increase in the plasma follicle stimulating hormone (FSH) and a decrease in the luteinizing hormone (LH). Testosterone was increased with the higher dose only while adrenocorticotrophic hormone (ACTH) was not altered by either one. These results suggest that the effects of caffeine on the two gonadotrophic hormones, FSH and LH, involve two separate pathways. The light microscope study revealed reduced sizes of the seminiferous tubules, inhibited spermatogenesis, fatty degeneration of the liver and hepatic lesions. The adrenal glands exhibited signs of stimulated steroidogenesis. It is concluded that long term intake of caffeine induces suppression of spermatogenesis mainly through inhibition of FSH release and this effect is maintained even in the presence of normal or high levels of testosterone and LH.

Use of cyproterone acetate to lower circulating corticosterone and its effects on lymphocytes in domestic fowl.

Chickens were given daily injections of cyproterone acetate (CA) and the effects on plasma corticosterone, bodyweight, weights of the adrenals and lymphoid organs, numbers of circulating peripheral blood lymphocytes and their proliferation in the presence of lectins, concanavalin A (Con A) and phytohaemagglutinin (PHA), were investigated. Five daily doses of 10 or 30 mg CA kg-1 bodyweight each week over a three-week period caused a decrease in weight gain and a reduction in the relative weights of the bursa and thymus but not the spleen. There was a small decrease in the adrenals after treatment with 10 mg CA kg-1. When daily injections of CA were given over a seven-day period doses of 6 and 10 mg CA kg-1 bodyweight caused a significant (P less than 0.05) decrease in plasma corticosterone concentration after four days. However, after eight daily injections of CA a single injection of corticotrophin (10 iu ACTH kg-1) increased circulating corticosterone indicating CA had not completely blocked adrenal synthesis. CA had no effect on numbers of circulating peripheral blood lymphocytes or their ability to proliferate in the presence of Con A or PHA. The results indicate that CA is effective in lowering circulating corticosterone in the fowl but this did not affect the numbers or responsiveness of peripheral blood lymphocytes.

Enhancement of the adrenocortical response to metyrapone by L-dopa in the chicken (Gallus domesticus).

1. Eight-week-old chickens were treated with a single intravenous injection of saline, L-dopa (20 mg/kg body weight), metyrapone (60 mg/kg) or a combined dose of L-dopa and metyrapone. Serum corticosterone was measured by radioimmunoassay at 30, 60 and 90 min after the treatment. 2. L-dopa did not alter the corticosterone concentration during the experiment, whereas metyrapone increased it at 60 and 90 min. 3. When L-dopa and metyrapone were given together there was a gradual increase in corticosterone and the hormone concentrations were significantly greater than control values at all times. 4. It was concluded that L-dopa is not a potent stimulator of adrenocortical cells in chickens, but it enhances the response to metyrapone. This may be achieved through the release of endogenous ACTH by stimulating central dopamine receptors.

Response of broilers and capons to heat stress following adrenal manipulation.

Five-week-old capons and normal broiler males were used in an experiment to test the effect of caponization and adrenal cortical manipulation on subsequent heat stress survival. Saline, adrenocorticotropin (ACTH) at 20 IU/kg, or metyrapone at 60 mg/kg was given daily at either 0730 or 1400 hr. No differences attributable to the time of injection were found. Prestress weights for all groups were not significantly different. Capons and sham-operated males receiving either the vehicle or metyrapone showed significantly higher heat stress mortality (P less than .01) than capons receiving ACTH. This suggests an important adrenal contribution in the ability of young chickens to withstand high environmental temperatures. The results also indicate that the susceptibility of male broilers to heat stress is not directly related to the testes.