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M H Mostafa

Publications and source records attributed to M H Mostafa.

At least 55 records · Page 3Linked to original sources
PubMed1984

Hepatic microsomal enzymes in S. mansoni infected mice: II. Effect of duration of infection and lindane administration on aminopyrine demethylase and aniline hydroxylase.

The time course of effects of S. mansoni infection on hepatic microsomal drug metabolizing enzymes was studied in swiss albino mice. Aminopyrine demethylase and aniline hydroxylase showed increases in activity, reaching a peak 30 days post infection. Both enzymes demonstrated a steady decline thereafter. On day 60, the level of aminopyrine demethylase was comparable to that of uninfected mice. On the other hand, the activity of aniline hydroxylase was lower than the control values. Treatment with lindane (40 mg/Kg/day X 3) increased the activity of both enzymes after different durations of disease induction. Changes in hepatic microsomal enzymes in S. mansoni infection may alter the intensity and duration of pharmacologic or toxic effects of drugs eliminated from the body through metabolic transformation.

Aminopyrine N-Demethylase↗
PubMed1983

Influence of pretreatment with various insecticides on the N-demethylation of dimethylnitrosamine.

The effects of various classes of insecticides were studied on the N-demethylation of dimethylnitrosamine (DMN) by mouse liver enzymes. Organochlorine insecticides, represented by lindane, DDT, and endrin, increased the activities of DMN demethylase I and II. The latter enzyme was more susceptible to the inducive action of the tested chlorinated insecticides. On the other hand, the synthetic pyrethroids, fenvalerate and flucythrinate, did not alter the activity of either enzyme. While pretreatment with carbaryl, a carbamate derivative, was without effect, moderate elevation in the activity of both demethylases was observed following administration of carbofuran. Dimethoate, representing organophosphorus compounds, was the only insecticide tested to inhibit the N-demethylation of DMN, with more pronounced effect on DMN demethylase I. Since DMN requires metabolic activation for its hepatotoxic and carcinogenic actions, alterations in the activities of its metabolizing enzymes as a sequela of exposure to certain insecticides may change susceptibility to its toxicity and/or carcinogenicity.

Animals↗
PubMed1983

Effect of some xenobiotics on kynurenine hydrolase and kynurenine aminotransferase of mouse liver.

The effects of some xenobiotics on the activity of the B6-dependent kynurenine hydrolase (KH) and kynurenine aminotransferase (KATE) in mouse liver, were investigated. Polychlorinated biphenyl (Aroclor 1254) (400mg/kg/day x4) markedly decreased the activity of both enzymes. Benzo(a)pyrene (BP) and 3-methylcholanthrene (3-MC) (40mg/Kg/day x1) as well as phenobarbital (PB) (75mg/kg/day x3) did not alter the activity of KH, while that of KATE was mildy reduced. The response of the two enzymes to treatment with chlorpromazine (CPZ) (5mg/Kg/day x5) were opposite with marked elevation of KH and inhibition of KATE activities. Treatment with B-naphthoflavone (B-NF) (80mg/Kg/day x2), Pyrazole (200mg/Kg/day x1) or indole (400mg/kg/day x1) produce no change in the activity of either enzyme. It, seems therefore, that Aroclor (1254) and chlorpromazine may cause disordered kynurenine metabolism through alterations in the activities of its metabolizing enzymes. This, in turn, might affect nicotinamide adenine dinucleotide biosynthesis and/or the accumulation of some tryptophan metabolites suspected of being carcinogenic or co-carcinogenic.

Animals↗
PubMed1983

Inhibitory effects of carbon tetrachloride on dimethylnitrosamine metabolism and DNA alkylation.

The effect of CCl4 pretreatment (dose range from 0.5 to 2.0 ml/kg body weight) on the pathways of dimethylnitrosamine (DMN) metabolism was investigated. The oxidative-N-demethylation by the enzymes, DMN-demethylase I and II operating at low (4 mM) and high (200 mM) substrate concentration, respectively, was greatly reduced in a dose-dependent manner. In addition, the generation of an electrophilic intermediate capable of methylating DNA, specifically at the N-7 and O-6 positions of guanine, was completely inhibited by CCl4 (0.5 ml/kg body weight) pretreatment. When indole feeding (1% in the diet for 8 days prior to CCl4 administration) was employed as a means to enhance DMN-demethylase activities, it was found that the reduction of DMN-demethylase activities was more pronounced in these rats than in the controls. In agreement with earlier findings, 7-methylguanine and O6-methylguanine were not detectable in the CCl4 pretreated group. These results suggest that CCl4 exerts a strong inhibitory action on hepatic DMN metabolism, in particular on the pathway leading to alkylation of DNA guanine. This phenomenon may explain the protective role of CCl4 against DMN-induced hepatotoxicity and perhaps, carcinogenicity, believed to be closely associated with the abnormal modifications of DNA.

Alkylation↗
PubMed1982

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).

Animals↗
PubMed1982

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.

Animals↗
PubMed1982

Effect and mechanism of action of methomyl and cypermethrin insecticides on kynurenine metabolizing enzymes of mouse liver.

The effect of methomyl and cypermethrin insecticides on the B6-dependent kynurenine hydrolase (KH) and kynurenine aminotransferase (KATE) was studied. These insecticides induced pronounced inhibition on the (KH) and (KATE) enzymes after single dose treatment. Repeated doses of methomyl induced inhibition on the (KH) and (KATE) activities, whereas repeated treatment with cypermethrin had no effect on the activities of these enzymes. In vitro methomyl inhibited (KH) and (KATE) enzymes at 10(-6)M up to 10(-3)M, through a competitive mechanism. Methomyl and cypermethrin are capable of causing alterations in the kynurenine metabolizing enzymes of mouse liver.

Animals↗
PubMed1982

Effect of fenvalerate on kynurenine metabolizing enzymes and acid ribonuclease of mouse liver.

The effects of fenvalerate, a pyrethroid insecticide, were studied on some mouse liver enzymes. Given orally, either in a single dose of 60 mg/kg or in a six daily doses of 20 mg/kg, fenvalerate reduced the activity of the B6-dependent kynurenine hydrolase (KH), but increased that of kynurenine aminotransferase (KATE) and beta-glucuronidase (beta-Glase). While the single dose treatment with fenvalerate had no effect on acid ribonuclease (RNase), the repeated treatments increased the activity of this enzyme. This study demonstrates that fenvalerate can alter the kynurenine metabolizing enzymes and acid ribonuclease of mouse liver.

Animals↗
PubMed1982

Production of kidney tumors in rats with low dose of dimethylnitrosamine after partial hepatectomy.

The occurrence of kidney tumors in inbred Wistar rats as a result of dimethylnitrosamine (DMN) administration at different intervals after partial hepatectomy was studied. The schedule for DMN administration was determined on the basis of the levels of liver dimethylnitrosamine demethylase (DMN-d) at different intervals after the operation. DMN-d was 62% of the control values at 24 hours. 72% at 72 hours, and 96% at 92 hours after the operation. At these intervals a single dose of DMN (10 mg/kg body wt) was given to partially hepatectomized animals and to untreated controls. At termination, when the animals were 94 weeks old, no kidney tumors were found in the control animals, whereas 23 of 54 animals (43%) that had been given injections of DMN 24 hours after partial hepatectomy developed kidney tumors. Kidney tumor incidence was 28 or 12%, respectively, when the carcinogen was administered 72 of 92 hours after the operation. The kidney tumor incidence and the activity of liver DMN-d were inversely related.

Animals↗
PubMed1981

The kinetic mechanism of inhibition of liver pyridoxal kinase with tryptophan metabolites.

The activity of purified liver pyridoxal kinase (ATP:pyridoxal 5-phosphotransferase, EC 2.7.1.35) was determined in the presence of 13 different tryptophan metabolites. Only 3-hydroxykynurenine, 3-hydroxyanthranilic acid, xanthurenic acid and quinolinic acid were found to inhibit the enzyme with I50 values of 0.1, 0.12, 0.36 and 0.42 mM, respectively. The inhibition was not related to the presence of pyridine nucleus in the metabolites molecule as was proved from the patterns of inhibition.

3-Hydroxyanthranilic Acid↗
PubMed1981

Urinary alpha-naphthyl acetate esterases: a preliminary screening test for bladder cancer.

The urinary activities of alpha-naphthyl acetate esterases were measured for groups of bilharzial and nonbilharzial patients with benign urologic diseases and for others with bladder cancer. All these patients showed elevation in the urinary enzyme activity over that given by healthy controls. Bilharzial and nonbilharzial bladder cancer patients exhibited significant increase in urinary enzyme activity as compared with corresponding groups with benign urologic diseases A level of 50 units of enzyme activity was taken as a limit to discriminate between bladder cancer patients and those patients with benign urologic diseases. The specificity and sensitivity of this urinary test exceeded 90% with low falsely positive and negative results. The data of the present study recommended the use of urinary alpha-naphthyl acetate esterases activity as a preliminary screening test for bilharzial and nonbilharzial bladder cancer patients.

Carboxylic Ester Hydrolases↗
PubMed1980

Effect of chlorpromazine hydrochloride on carcinogen-metabolizing enzymes: liver microsomal dimethylnitrosamine demethylase, 4-dimethylaminoazobenzene reductase, and aryl hydrocarbon hydroxylase.

Investigation of the effect of chlorpromazine hydrochloride (CPZ) on some enzymes involved in the metabolism of the carcinogens 4-dimethylaminoazobenzene (DAB), benzo[a]pyrene, and dimethylnitrosamine (DMN) revealed that CPZ inhibited hepatic microsomal DAB reductase, aryl hydrocarbon hydroxylase, and DMN demethylase II but markedly activated DMN demethylase I. Inhibition of these enzymes in vitro was proportional to the concentrations of CPZ. The effect of CPZ on DMN demethylase also depended on the concentrations of DMN and CPZ in the incubation mixture. Mechanisms to account for the inhibition of DAB reductase were suggested. Aryl hydrocarbon hydroxylase and DMN demethylase II activities of the 100,000 x g hepatic microsomal fraction were activated by 33 and 61%, respectively, over the control values after a single injection of CPZ into F344 rats, but no effect on DAB reductase and DMN demethylase I activities was observed. Microsomal concentrations of protein and cytochrome P450 were not appreciably altered by CPZ treatment, whereas the level of microsomal NADPH cytochrome c reductase was slightly increased over control values. A similar effect on the drug-metabolizing enzymes was found during pretreatment of rats with CPZ for 5 days, except that the NADPH cytochrome c reductase was increased by 33% over the control values.

Animals↗