Comparative effects of chronic administration of some psychotropic drugs on rat brain cortex acetylcholinesterase activity.

The response of central cholinergic neurotransmission to the chronic administration of some psychotropic drugs to rats was investigated using brain acetylcholinesterase activity as a neurochemical marker for cholinergic neurons. Rats were divided into four groups. Three experimental groups were given chlorpromazine, amitriptyline, or diazepam respectively, for a period of 30 days; and the control group received physiological saline only. Long-term treatment of chlorpromazine and amitriptyline resulted in significant increases in rat brain cortex enzyme activity, whereas only a slight increase was observed in the diazepam-treated group. These results indicate that the chronic treatment with some psychotropic drugs causes changes in central cholinergic transmission.

Liver delta-aminolevulinate dehydratase activity in amitriptyline- or chlorpromazine-treated rats.

Amitriptyline (AMT) and chlorpromazine (CPZ) (0.5 mg per animal, i.p.) were injected into rats separately for 30 days and their effects on heme metabolism in liver were examined. Significant decreases in the delta-aminolevulinate dehydratase activity were observed following the administration of both drugs (mean value of AMT-group: 6.58 U/g tissue; and CPZ-group: 7.04 U/g tissue) in comparison to that of controls (11.71 U/g tissue); however total liver heme content was not altered. When 24-h urinary excretions of delta-aminolevulinate (ALA) and porphobilinogen (PBG) were measured on the last day of the experiment, a slight (AMT-group: 38.40 micrograms/day) to distinct (CPZ-group: 59.11 micrograms/day) increase of urinary ALA was observed, while PBG excretion tended to decline only moderately under CPZ (3.52 micrograms/day), but significantly in presence of AMT (2.16 micrograms/day). Mean values obtained from control group were 32.12 micrograms/day for ALA and 4.25 micrograms/day for PBG.

Gamma-glutamyl transpeptidase and acetylcholinesterase activities in brain capillaries of cholesterol-fed rabbits.

Cerebral microvascular endothelium, the constituent cell of the blood-brain barrier, is enriched in the enzyme gamma-glutamyl transpeptidase (GGT). This enzyme plays a role in the regulation of amino acid uptake and transport, and in the gamma-glutamylation of serotonin, dopamine and norepinephrine. Recent studies have demonstrated that GGT activity is modulated by cholinergic-adrenergic agonists. The levels of the acetylcholine-catabolizing enzyme acetylcholinesterase (AChE), may therefore be related to the modulation of the GGT activity. In this study, the activities of GGT and AChE in microvessel-enriched fractions were assayed after feeding of rabbits a high cholesterol diet. A 21% decrease of GGT activity and a 44% increase of AChE activity appeared at the end of dietary treatment.

Modulation of gamma-glutamyl transpeptidase activity by dietary eicosapentaenoic acid and vitamin E in livers of rabbits on hypercholesterolemic diet.

Rabbits were fed high-cholesterol diets containing either eicosapentaenoic acid (EPA) or vitamin E at doses of 80 mg and 100 IU per day, respectively. Liver gamma-glutamyl transpeptidase (GGT) activity and liver cholesterol and phospholipid levels were determined following the administration of the diets for 45 days. The feeding of cholesterol produced the highest concentrations of cholesterol in livers accompanied with the elevated enzymatic activity. Addition of EPA to the diet dramatically reduced GGT activity to normal levels, whereas vitamin E administration caused only a slight reduction.

Influence of eicosapentaenoic acid and vitamin E on hepatic hydroxyproline content in rabbits fed cholesterol-rich diet.

The effect of eicosapentaenoic acid (EPA) and vitamin E on hepatic hydroxyproline content, as an index of collagen was examined in rabbits receiving cholesterol rich diets for a period of 45 days. Rabbits were divided as control (A) and cholesterol fed groups (B, C, D). Group C received 80 mg. of EPA and group D received 100 IU of vitamin E daily in addition to the cholesterol rich diet (2% w/w) which was solely given to group B. The maintenance of rabbits on high cholesterol diets resulted in significantly increased liver cholesterol concentrations. This effect was most pronounced in rabbits receiving cholesterol alone. Hepatic triglyceride levels remained unchanged in all cholesterol-fed rabbits, but total phospholipid levels in liver significantly decreased in EPA and vitamin E supplemented rabbits. An interesting finding was the increase in hepatic hydroxyproline content in rabbits following the administration of EPA and vitamin E to cholesterol rich diet.

Influence of eicosapentaenoic acid and vitamin E on brain cortex Ca2+ ATPase activity in cholesterol-fed rabbits.

The influence of eicosapentaenoic acid (EPA) and vitamin E on brain cortex Ca2+ ATPase activity was examined in rabbits receiving cholesterol-rich diets for a period of 45 days. Rabbits were divided as control (A) and cholesterol-fed groups (B, C, and D). Group C received 80 mg of EPA and group D received 100 IU of vitamin E every day in addition to the cholesterol-rich (2%, w/w) diet which was solely given to Group B. Rabbits receiving cholesterol alone had a significant reduction in brain microsomal phospholipid level. Microsomal free cholesterol and polyunsaturated fatty acids (PUFA) were significantly increased in all experimental groups. Cortex microsomal Ca2+ ATPase activity was found to be inhibited in all cholesterol-fed rabbits as compared to controls, but the highest inhibition was seen in rabbits fed cholesterol alone. Additions of EPA or Vitamin E to the cholesterol-rich diets resulted in a recovery of the enzymatic activity. It is concluded that cholesterol feeding without any addition of PUFA or antioxidant agent might cause an inhibition of brain Ca2+ ATPase activity in rabbits, thereby leading to the dysfunction in ion transport and neurotransmitter release.

Liver gamma-glutamyl transpeptidase activity following chronic treatment with acetylsalicylic acid in rats.

In the present study, rats were administered acetylsalicylic acid (ASA), at low and high doses, by means of a gastric tube for 30 days. Chronic administration of a high dose of ASA (200 mg/kg body weight) resulted in a significant increase in liver plasma membrane gamma-glutamyl transpeptidase activity, cholesterol, and phospholipid levels. The enzymatic activity and lipid levels appeared not to be affected by ASA when given at a lower dose (50 mg/kg body weight). The changes in the enzymatic activity of plasma membrane were positively correlated to membrane cholesterol content. These findings suggest that the hepatotoxicity of high doses of ASA should not be overlooked during clinical use of the drug.

Activity of gamma-glutamyl transpeptidase in human fetal membranes.

The presence of gamma-glutamyl transpeptidase in human fetal membranes and alterations in enzyme activity during the gestational period were studied. Fetal membranes from term deliveries exhibited a high enzymatic activity, whereas membranes from preterm deliveries showed alterations with regard to the gestational weeks. These alterations were found to be similar to those which had previously been obtained from rat placentae during fetal growth and development.

Gamma-glutamyl transpeptidase alterations in liver and serum induced by haloperidol.

Changes in the activity of the microsomal enzyme gamma-glutamyl transpeptidase (GGT) were examined in liver and serum following subacute and chronic haloperidol administration to rats. Haloperidol increased both serum and liver GGT levels. The enzymatic activity returned to baseline values on the sixth day after withdrawal of the drug. It is concluded that alterations in serum GGT levels may be expected during prolonged treatment of haloperidol, and that these alterations reflect enzyme induction in liver microsomes where the drug is entirely metabolized.