Glutathione S-transferase activity and glutathione content in human bladder carcinoma associated with schistosomiasis: comparison with uninvolved surrounding tissues.

Glutathione (GSH), glutathione S-transferase (GST) activity and GSTpi expression were measured in 10 human bladder tumors and adjacent uninvolved specimens from Egyptian patients with a history of schistosomal infection. GSH was higher in the tumor than in surrounding uninvolved tissue (not significant). Total GST activity per mg tissue protein and GSTpi expression were higher in tumor tissues (P < 0.05) than in uninvolved tissues. There was a positive correlation between GST activity and GSH content and between total GST activity and GSTpi expression in both tumor and uninvolved tissues.

In vivo and in vitro studies on the effects of some phenothiazines and sulpiride on kynurenine metabolism.

The effect of 5 consecutive daily i.p. doses of CPZ (5 mg/kg), PZ (10 mg/kg) and PMZ (10 mg/kg) on the activity of kynurenine hydrolase and kynurenine aminotransferase in mouse liver was studied. All three phenothiazines effected an increase in the activity of kynurenine hydrolase per unit weight of liver with CPZ showing the highest activation followed by PZ and PMZ. On the other hand kynurenine aminotransferase was more moderately inhibited by the above treatment. In vitro studies showed that the phenothiazines tested and the pharmacologically inactive CPZO, the major metabolite of CPZ, in concentrations ranging from 3 X 10(-9) to 3 X 10(-4) M had an activating effect on kynurenine hydrolase. Increases in activity were obtained up to concentrations of 3 X 10(-6) M and levelled off afterwards. The highest increases were observed with CPZ and CPZO, while those of PZ and PMZ were of lesser magnitude. However, the tested phenothiazines were without effect on kynurenine aminotransferase. The newly introduced psychotropic drug, sulpiride, which is a substituted benzamide, was devoid of activity on either enzyme both in vivo (50 mg/kg) and in vitro (3 X 10(-9) to 3 X 10(-4) M).

In vivo effect of chloramphenicol and thiamphenicol on some enzymes of normal mouse liver.

Chloramphenicol a potent inhibitor of bacterial and some mammalian cell protein synthesis, was administered i.p. to a group of mice for 6 consecutive days. Another group of animals was treated similarly with thiamphenicol and a third group served as control. The effects of the two antibiotics on the activity of some liver enzymes; the two pyridoxal 5-phosphate dependent enzymes, kynurenine hydrolase and kynurenine amino-transferase; pyridoxal phosphokinase; beta-glucuronidase and acid ribonuclease were determined. Chloramphenicol and thiamphenicol decreased significantly the activities of kynurenine hydrolase, beta-glucuronidase and acid ribonuclease and both drugs increased the activity of pyridoxal phosphokinase significantly. Their effect on kynurenine amino-transferase was different, chloramphenicol decreased while thiamphenicol increased the enzyme activity. Results are discussed and possible explanations suggested.

The activity of serum ribonuclease in protein-energy malnutrition.

Serum alkaline ribonuclease activity and serum albumin concentration were determined in 25 normal children and 59 children with protein-energy malnutrition. The increase in serum ribonuclease was marked in marasmus and marasmic kwashiorkor. The ribonuclease activity dropped significantly after two weeks of treatment and returned to normal by four weeks. In kwashiorkor, serum ribonuclease activity was significantly lower than control and returned to normal after four weeks of treatment. These findings support previous observations that the serum ribonuclease is a good criterion of the nutritional status and indicates that the enzyme activity, particularly when related to serum albumin, is a good prognostic index in this respect.

Serum and urinary ribonuclease in children with schistosomal hepatic fibrosis.

Serum and urinary RNase activity was determined in 15 normal children and in 52 children in various clinical stages of schistosomal hepatic fibrosis. The activity of serum RNase was compared with that of serum GOT, GPT and AP. The activity of serum and urinary RNase in the different schistosomal groups was significantly higher than in healthy children. The elevated levels of serum and urinary RNase activity were possibly due to malnutrition with tissue catabolism, zinc-deficiency and liver cell injury. Treatment with Astiban and protein-rich diet resulted in a significant decrease in serum and urinary RNase activity and an in significant drop in serum GOT, GPT and AP. Serum and urinary RNase appear to be more sensitive indices for evaluating the early metabolic disturbances in schistosomal patients than GOT, GPT or AP. Our findings also showed that the severity of cases could be graded according to the level of urinary RNase.

The activities of urinary alpha-esterases in bilharziasis and their possible role in the diagnosis of bilharzial bladder cancer in Egypt.

The activities of serum and urinary alpha-esterases were studied in 49 bilharzial bladder cancer patients, 92 bilharzial patients with other, different, urologic diseases and 22 normal healthy controls. Among the group studied, the bilharzial bladder cancer patients showed the highest level of urinary-alpha-esterases and the lowest ratio of serum/urine activity. These patients showed a significant increase in the activity of urinary alpha-esterases as compared with the normal controls or with the other different bilharzial groups. Although a small but significant increase in serum activity was observed in all the bilharzial groups studied compared with the normal healthy controls, no significant difference was found between the bilharzial bladder cancer patients and the other different bilharzial groups. Biochemical determination of urinary alpha-esterases for bilharzial patients revealed a high degree of accuracy for the diagnosis of bilharzial bladder cancer (95.9%), with low falsely positive (3.26%) and falsely negative (4.08%) results. The activity of urinary alpha-esterases in recommended as a screening test for bilharzial bladder cancer.

Effect of gossypol on liver metabolic enzymes in male rats.

The effects of gossypol on liver metabolism were examined in male rats. Gossypol acetic acid was administered to Sprague-Dawley rats intraperitoneally (i.p.) at 5 mg/kg daily, 5 days/week for 2 weeks. The rats were killed 24 h after the last injection. The liver/body weight ratio (-42%), concentration of liver glutathione (-34%), activities of liver alpha-naphthtylacetate esterase (-30%) and DNase (-39%) were significantly decreased when compared to controls. Hepatic beta-glucuronidase (+37%), RNase (+35%) and serum alkaline RNase (+23%) activities were significantly increased. No changes were found in serum transaminases (SGPT, SGOT) or in hepatic RNA and DNA concentration. Elevation of liver and serum RNase activities suggest that gossypol treatment produces some catabolic effects. The depletion of hepatic glutathione and the elevation of beta-glucuronidase activity indicate that gossypol is hepatotoxic when given at this dose for 2 weeks.

Steroidal thiourea and thiazoline derivatives: synthesis and in vitro effects on bovine pancreatic ribonuclease activity.

Two novel series of steroidal derivatives containing various thiourea and substituted thiazoline moieties attached to the 2- or 4-position of estrone were synthesized and examined for in vitro effect on bovine pancreatic ribonuclease activity. All compounds studied exhibited a catabolic activity. The steroidal thiazoline derivatives were more potent activators of ribonuclease than the steroidal thioureas.

Steroidal derivatives. Part 4: Synthesis and in vitro anabolic and catabolic properties of a new group of steroidal alkylating agents.

A new group of steroidal alkylating agents has been synthesized for potential anticancer activity. The compounds contain a sulfonic ester, a mono- or a bifunctional nitrogen mustard function attached to an ethyl chain and forming ether linkages at the 3- or 17 beta-position of the steroids selected. The products were tested for their in vitro anabolic and catabolic properties by measuring their effects on the bovine pancreatic ribonuclease.

Biochemical effects of vinyl chloride monomer on the liver of occupationally exposed workers.

We investigated the effects of vinyl chloride monomer exposure on the liver of 86 workers by measuring beta-glucuronidase, arylsulfatase A, adenosine deaminase, 5'-nucleotidase and routine liver function enzymes in the sera of the workers. In 21 of them, three or more of these parameters were raised, with a significant decrease in the level of blood glutathione and a significant increase in the enzyme activity level of glutathione S-transferase. Of these 21 workers, 14 had fatty liver infiltration, 8 of whom were also suffering from liver enlargement. Also, 4 workers had liver enlargement without fatty infiltration and 3 had enlarged spleens. The study highlights the need for vigilance in environmental monitoring and medical surveillance of workers exposed to this chemical.

The effect of dimethylnitrosamine on the activities of renal prenolsulfotransferase and arylsulfatases A and B in Schistosona mansoni infected mice.

The activities of renal phenolsulfotransferase and arylsulfatases A and B were estimated in 400 male Swiss albino mice classified into four groups: Normal controls, Schistosoma mansoni infected group, Dimethylnitrosamine (DMN) treated group and infected treated group. The activity levels of the studied enzymes were significantly increased in all groups when compared with the control group, also the statistical analyses showed a high significant increase of the three enzymes levels in the infected treated group; when compared separately with treated or infected groups. It was concluded, therefore, that schistosomal infection is implicated in the development of kidney cancer which may arise from the pattern of hepatic mixed-function oxidase induction characterized for schistosomiasis and its temporal relationship with the procarcinogenic initiating events. Furthermore, the striking significant increase in the enzymatic activity levels of the acid hydrolases arylsulfatases due to the lesion of both cytotoxic effects of dimethylnitrosamine as well as pathological change of schistosomiasis which may play an active role in the initiation of the malignant process by detoxifying endogenous sulfated aromatic metabolites.

Effect of chlorpromazine free radical on tyrosine hydroxylase of bovine adrenal medulla.

The effect of preincubation with chlorpromazine and chlorpromazine free radical on tyrosine hydroxylase activity was studied. Chlorpromazine free radical inhibited the enzyme activity to a greater extent than chlorpromazine. More than a two-fold decrease in the enzyme activity was observed following the preincubation of the enzyme with chlorpromazine free radical. This observation may suggest interaction between chlorpromazine free radical and -SH group located on the active site of the apoenzyme. Another interaction between chlorpromazine free radical and the coenzyme (DMPH4) was confirmed from spectral studies.

In vitro effect of dimethoate on the activity of tryptophan pyrrolase in rat liver.

Total and holo-enzyme activities of tryptophan 2,3-dioxygenase were measured in vitro in the presence and absence of the organophosphorous insecticide, dimethoate. Addition of dimethoate to the reaction mixture decreased the activities of both total and holo-forms. Total and holo-enzyme activities were decreased by 34% and 26%, respectively, by 1 mM dimethoate. On the other hand, 5 mM dimethoate resulted in 56% and 34% inhibition to total and holo-enzyme activities, respectively. Lineweaver-Burk plot of the total-enzyme activity at different tryptophan concentration in the presence of 2 mM dimethoate gave uncompetitive type of inhibition.