Effect of lithium on rat cerebrum under different dietary protein regimens.

This study was designed to investigate the effects of lithium in adult rat brain under different dietary protein regimens. Lithium as carbonate was given at a dose of 1.1 g/kg diet to female rats fed normal (18% protein), low protein (8% protein), and high protein (30% protein) diets for 30 days. Lithium treatment resulted in a significant decrease in the levels of norepinephrine, dopamine, and serotonin in the cerebrum of the rat brain. Further, administration of lithium to rats fed low protein (LP) and high protein (HP) diets also showed a significant decrease in the levels of norepinephrine and dopamine but caused no significant change in the serotonin concentration. Lithium administration to normal diet, LP, and HP groups resulted in a significant increase in the activities of acetylcholinesterase and monoamine oxidase. Lithium treatment led to decrease in the activity of enzyme Na+ K+ ATPase in all groups. On the second day, the LP group showed enhanced transfer latency (TL), a dependent variable to study elevated plus-maze test, whereas HP diet went from 34% reduction to normal. On the other hand, lithium administration restored the already enhanced TL in the LP group. The study concludes that lithium treatment to protein-deficient cases may not further aggravate the effects of protein-deficient conditions, but it may afford protection.

Changes in the chemical composition of surfactant-like particles secreted by rat small intestine in response to different dietary fats.

Consumption of dietary oil, viz., corn, fish, coconut, or olive, induced the secretion of surfactant-like particles (SLP) in rat intestine. These lipoprotein particles differ in (i) levels of alkaline phosphatase activity, (ii) lipid composition, and (iii) FA composition in response to feeding of different oils. The secreted particles had similar buoyancy (1.07-1.08 g/mL) and cholesterol/phospholipid molar ratios (0.61-0.72) except that feeding coconut oil to rats produced SLP with a low (0.18) cholesterol/phospholipid molar ratio compared to control animals. It is concluded from these observations that feeding different oils induces the secretion of lipoprotein particles in rat intestine with different chemical compositions.

Formation of surfactant-like-particle in rat intestine following chronic ethanol feeding.

Ethanol feeding to rats daily for 40 days induces the secretion of surfactant-like-particles in intestine. The isolated lipoprotein particles were enriched with alkaline phosphatase activity and had high phosphatidylcholine content. There was no difference in disaccharidases activities associated with the particles from control and ethanol fed rats. These results suggest that ethanol induced surfactant-like-particles in rat intestine.

Functional role of sialic acid in IgG binding to microvillus membranes in neonatal rat intestine.

A close parallelism exists between sialylation and endocytotic activity of the small intestine during postnatal development in rats. Thus, the binding of 125I-labelled IgG to microvillus membranes and its relationship to membrane sialic acid has been studied in suckling rat intestine, during (a) postnatal development; (b) cortisone-induced precocious maturation, and (c) after desialylation of brush borders by neuraminidase treatment. Neuraminidase-treated membranes exhibited low (42%, p < 0.001) IgG binding. The observed decrease in IgG binding to desialylated membranes was associated with a decrease in the value of affinity constant, (-Ka = 0.4 x 10(6) M-1 in control and 0.23 x 10(6) M-1 in desialylated membranes). The number of IgG-binding sites (2.3 nmol/mg protein) was unchanged under these conditions. A similar decrease (50%) in IgG binding to brush borders was also observed in cortisone-injected pups. This was associated with reduced sialic acid (37%) content of the membranes compared to the controls. The value of -Ka was reduced from 0.4 x 10(6) M-1 in the control to 0.3 x 10(6) M-1 in the hormone-injected pups. The number of binding sites (n) was decreased from 2.2 to 1.4 nmol/mg protein under these conditions. Low concentrations of calcium (0.1-1.6 mM) in the incubation medium enhanced IgG binding (p < 0.001) to brush borders in pups but there was no change in binding of IgG to the membranes at 2 mM Ca2+ concentration compared to controls. Addition of Zn2+ or Mg2+ did not affect IgG binding under these conditions. These findings suggest a functional role of Ca2+ and sialic acid residues of the membrane glycans in IgG-receptor interactions in suckling rat intestine.

Effect of lithium on hepatic and serum elemental status under different dietary protein regimens.

Lithium carbonate at the dose level of 1.1 g/kg was administered in diet to normal (18% protein), low-protein- (LP; 8%) and high-protein (HP; 30% diet)-fed rats for a period of 1 mo. The LP diet resulted in a significant decrease in the hepatic levels of zinc, iron, copper, manganese, calcium, and serum levels of calcium and sodium. The HP diet caused a marked decrease in copper and calcium levels in liver, but an increase in potassium levels in serum was observed. Lithium treatment to normal rats led to a significant reduction in the hepatic contents of zinc, copper, potassium, calcium, and serum contents of potassium and sodium, whereas an elevation in serum contents of calcium was noticed. Administration of lithium to protein-deficient rats increased the hepatic concentration of manganese and serum concentration of calcium and the levels almost reached the normal limits. On the other hand, there was a marked depression in potassium contents in the serum of LP- as well as HP-fed rats following lithium treatment when compared to LP and HP groups, respectively.

IgG binding and expression of its receptor in rat intestine during postnatal development.

The binding of 125I labelled IgG to the microvillus membranes (MVM) has been studied during postnatal development of rat intestine. The levels of mRNA encoding IgG receptor were also analyzed by liquid hybridization under these conditions. The IgG binding to MVM reached maximum levels by day 12 and showed a gradual decline upon weaning. The FcRn mRNA was markedly low in adult rats and was maximum during second week of postnatal development. Administration of cortisone or thyroxine to suckling rats, induced precocious decline of both IgG binding and the receptor expression. However, insulin administration did not affect the receptor expression. Scatchard analysis of IgG binding to MVM in cortisone injected pups revealed that the observed inhibition in IgG binding was a consequence of a decrease, both in the affinity constant (-Ka) as well as in the number of receptor sites (n) while thyroxine administration caused a reduction in the number of receptor sites from 2.29 in control to 1.14 nmoles/mg protein in thyroxine injected pups. These observations indicate that expression of IgG receptor during postnatal development is a hormone regulated process.

Harmaline interactions with yeast invertase.

The effect of harmaline, a plant alkaloid has been studied on yeast invertase activity in the absence and presence of 50mM Na+ as a function of pH. Harmaline (1-3 mM) inhibited the invertase activity at pH 5.2, 6.8 and 8 both in the absence (44-92%) and (22-85%) of Na+ ions. Kinetic analysis revealed that harmaline is a non-competitive inhibitor of invertase, at pH 5.2 and 6.8 but at pH 8, it produced a mixed type of inhibition, Km increased by 450% and 175% and Vmax decreased by 82% and 63% in the absence and presence of 50mM Na ions respectively. The observed inhibition of invertase by harmaline was reversible in nature. These findings suggest that the presence of Na+ site is not a prerequisite for the inhibition of enzyme by harmaline.

Effect of lithium on hepatic lipid peroxidation and antioxidative enzymes under different dietary protein regimens.

Lithium in the form of lithium carbonate was administered at a dose level of 1.1 g kg(-1) food to rats fed normal (18% protein), low-protein (LP; 8%) and high-protein (HP; 30%) diets for a period of 1 month. A highly significant (53%) increase in the level of lipid peroxidation (LPO) was observed in protein-deficient rats but this increase was marginal in rats fed an HP diet (18%). Lithium treatment of rats fed a normal diet caused a marked decrease (22%) in LPO. Lithium administration to rats fed an LP diet also reduced the raised levels of LPO to the extent of 16%. Furthermore, lithium treatment normalized the HP-induced increase in the levels of LPO. The activities of glutathione peroxidase (GPx), catalase and superoxide dismutase (SOD) were reduced significantly in protein-deficient rats. On the other hand, an HP diet caused a decrease in SOD activity only. The activities of GPx and catalase were appreciably enhanced in lithium-treated rats. Lithium treatment to LP-fed rat markedly increased GPx activity and brought the decreased levels of SOD and catalase to within normal limits. Lithium administration to HP-fed rats did not cause any significant alteration in the activities of these antioxidative enzymes.

Effect of lithium on hepatic drug-metabolizing enzymes of protein-deficient rats.

Protein deficiency was produced by feeding synthetic 8%-protein diet. Lithium carbonate at the dose level of 1.1g/kg diet was administered to normal and protein-deficient rats for a period of one mo. A significant inhibition in the levels of cytochrome (cyt) P450, cyt b5, glutathione (GSH), glutathione S-transferase (GST) and glutathione peroxidase (GPx), but an increase in gamma-glutamyl transpeptidase (gamma-GT), was observed in low-protein LP-fed rats. Lithium treatment to normal rats caused no significant change in the activities of cyt P450, cyt b5, GST, and GSH levels, whereas there was elevation in the activities of gamma-GT and GPx and suppression in glutathione reductase (GRd) activity. Lithium administration to LP-fed rats resulted in significant increases in the hepatic gamma-GT and GPx activities.

Hematological alterations in propylene glycol-dosed female rats are minimal.

The effect of a single oral dose of 73 or 294 mg propylene glycol/100 g bw, in Group I or II respectively, on hematological parameters, plasma osmolality and erythrocyte morphology was investigated in groups of 6 female rats each at different time intervals after dosing. A statistically significant and progressive decrease was observed in hemoglobin, packed cell volume and red cell counts for 2 d, which returned to basal values on the 8th day. Reticulocyte counts, plasma hemoglobin and osmolality increased after PG dosing in both the groups, and the changes were more pronounced after 2 d. The osmotic fragility of erythrocytes remained unaffected after PG dosing whereas electron microscope morphology revealed rough cell surface, ruptured membranes and increased cell adherence throughout the observation period, but these features were not marked on the 8th day. These modified red cell surface characteristics could promote removal by the reticulo-endothelial system resulting in the significant increases in spleen weight in both groups.

Dietary protein regimens and chronic ethanol administration effects on sodium- and proton-dependent solute uptake in rat intestine.

The effect of feeding ethanol daily for 40 days has been studied on intestinal uptake of glucose, glycine, and leucine in rats fed control, 8% protein (LP), and 30% protein (HP) diets. Na(+)-dependent uptake of glucose and glycine both at pH 7.2 and pH 5.5 was significantly depressed (p < 0.001) in ethanol or LP diet-fed animals and remained unaffected in HP-fed rats compared to the controls. But ethanol administration to protein-malnourished rats enhanced the Na(+)-linked glucose and glycine uptakes. Leucine uptake remained unaffected under these conditions. Glucose uptake remained unaltered whereas glycine uptake was reduced when ethanol was administered to rats given HP diet. In the absence of Na+, uptake of glucose, glycine, and leucine was more at acidic pH compared to that at pH 7.2 under all the experimental conditions investigated. Proton-linked uptake of solutes was unaffected by feeding ethanol, LP, or HP diet in rats. Thus, chronic ethanol feeding specifically depresses the Na(2+)-dependent uptake of glucose and glycine. Dietary protein content modifies ethanol effects on intestinal solute uptake in rats.

Effect of chronic ethanol administration and dietary protein regimens on intestinal absorption of macromolecules in rats.

The effect of feeding ethanol daily for 40 days has been studied on intestinal absorption of bovine serum albumin (BSA) and gamma-globulin (IgG) in rats fed a low (8%) protein (LP) or a high (30%) protein (HP) diet. Feeding the LP diet enhanced the tissue uptake of BSA (p < 0.05) and absorption of BSA and IgG into serum (p < 0.001) as compared with controls. Feeding the HP diet also augmented the uptake of IgG (p < 0.001) by the intestinal tissue and significantly enhanced serum levels of BSA and IgG. Ethanol feeding to rats for 40 days enhanced the uptake of BSA and IgG (24-84%) and their absorption into serum (p < 0.001) as compared with the controls. Ethanol administration to rats fed LP or HP diets did not alter the uptake of these proteins as compared with their respective controls. Luminal degradation of BSA and IgG was higher in ethanol-administered (48-50% and 36-39%, respectively) and LP-fed rats (50 and 38%, respectively). It was reduced by 17-21% in HP-fed rats as compared with the control group. This indicated that the observed increase in protein absorption is not related to the luminal degradation of the proteins under these conditions. These findings suggest that the absorption of macromolecules from intestine in response to ethanol feeding is influenced by the dietary status of the animals.

Expression of brush border enzymes in ethanol fed rat intestine.

The effect of feeding ethanol daily for 40 days was studied on various brush border enzymes in rat intestine. Brush border alkaline phosphatase (AP), lactase, gamma-glutamyltranspeptidase (gamma-GTP), p-nitrophenyl (PNP)-beta-D-galactosidase (P < 0.01) and sucrase (P < 0.001) were significantly enhanced while leucine aminopeptidase and PNP-beta-D-glucosidase activities were unaltered in ethanol fed rats compared to the controls. Kinetic studies revealed that an increase in Vmax together with a decrease in affinity in case of gamma-GTP and an increase in Vmax for AP and sucrase were responsible for the observed stimulation of enzyme activities in ethanol administered rats. Significant changes in enzyme activities were observed in different populations of enterocytes along the crypt-villus unit in the ethanol fed animals. These observations suggest that ethanol feeding modifies the brush border enzymes in rat intestine but the underlying mechanisms seem to be distinct in differentiating enterocytes.

Effect of chronic ethanol administration on the absorptive functions of the rat small intestine.

Ethanol feeding to rats for 40 days significantly (p < 0.01) depressed sodium-stimulated glucose and glycine uptakes at pH 5.5 and 7.2 without affecting sodium-independent solute transport in the rat intestine. Leucine uptake was essentially unaltered under these conditions. Absorption of bovine serum albumin and gamma-globulin as detected by enzyme-linked immunosorbent blocking assay (ELISA) was markedly augmented (p < 0.001) in ethanol-fed rats compared to the controls. These observations suggest that chronic ethanol intake differentially affects the uptake of organic solutes and macromolecules in the rat intestine.

Effect of propane-1,2-diol ingestion on carbohydrate metabolism in female rat erythrocytes.

This study was undertaken to assess the effect of propane-1,2-diol(PD) ingestion on carbohydrate metabolism in female rat erythrocytes. For this purpose, two different groups of adult albino female rats were treated orally with PD at two different dose levels of 73 and 294 mg 100 g-1 body wt. The blood samples drawn from the retro-orbital sinus prior to the treatment served as the controls, whereas the treated samples were collected at peak periods (1/2 and 2 h) 2 and 7 days after the treatment. A single dose of PD was found to elevate levels of blood glucose, lactate, pyruvate and the lactate/pyruvate ratio at the peak periods (P < 0.001) and after 2 days (P < 0.001) in both the groups. A significant (P < 0.05) increase in the contents of erythrocyte 2,3-diphosphoglycerate (2,3-DPG) was observed only at the peak periods. All these parameters returned to their base level after 7 days of treatment. The activities of hexokinase (HK), 2,3-diphosphoglycerate phosphatase (2,3-DPG Pase), lactate dehydrogenase (LDH), glucose-6-phosphate dehydrogenase (G-6-PD), 6-phosphogluconate dehydrogenase (6-PGD) and aldehyde reductase II (AR II) declined markedly, whereas those of pyruvate kinase (PK) and aldose reductase increased as a result of PD ingestion. The changes in the activities of 2,3-DPG Pase and LDH were persistent up to 8 days post-treatment. The [14C]glucose flux through glycolysis and the hexose monophosphate shunt pathway in erythrocytes was found to be lowered (P < 0.001) in response to PD treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic ethanol feeding and microvillus membrane glycosylation in normal and protein-malnourished rat intestine.

Ethanol feeding to rats for 40 days enhanced (p < 0.001) the activities of alkaline phosphatase, sucrase, gamma-glutamyltransferase (GTP), and p-nitrophenyl (PNP)-beta-D-galactosidase (p < 0.05) with no change in leucine amino peptidase (LAP) and PNP-beta-D-glucosidase activities in intestine compared with control rats. The activities of alkaline phosphatase, sucrase, and GTP were diminished (p < 0.01) in ethanol-fed malnourished rats. There was no change in LAP activity, but the levels of glucosidase and galactosidase were elevated under these conditions. Brush-border sialic acid, fucose, hexose, and hexosamine contents were elevated in ethanol-fed protein-deficient animals. Ethanol administration to normally fed rats elevated the membrane sialic acid and hexose contents, reduced fucose content, and had no effect on brush-border hexosamine content compared with the control group. These results are in agreement with data on lectin binding to brush borders under these conditions. Alcohol ingestion reduced the incorporation of [14C]-glucosamine into brush borders in rats maintained on an 18% protein diet but augmented the incorporation of [14C]-glucosamine and [14C]-mannose in protein-malnourished membranes. These observations suggest that nutrition status influences the sensitivity of microvillus membrane glycosylation to ethanol feeding in rat intestine.

The role of propylene glycol metabolism in lactatemia in the rabbit.

Propylene glycol (1,2-propanediol PD) has been reported to significantly alter the blood parameters when administered as a drug vehicle. In this study, experiments were performed to estimate the pH, levels of PD, and its metabolites to determine the acute effect of PD in blood. PD was administered to rabbits orally in a single dose of 1 ml 28.4% aqueous solution per 100 g body weight equivalent to 38.66 mmol/kg. Whole blood pH and the levels of PD and metabolites were estimated at fast (O.O h, before feeding PD) and at 0.25, 1, and 3 h after the dose. PD elevated the concentrations of blood PD to its maximum (41.04 +/- 9.98 mmol/liter, n = 4) at 1 h; whereas blood PD is normally absent during fasting. PD significantly increased (P less than 0.01) the concentration of L-lactate in blood, which reached its plateau (2.55 +/- 0.62 mmol/liter, n = 4) at 0.25 h and was 2.45-fold higher than the observed fasted values (1.04 +/- 0.22 mmol/liter, n = 4). Production of D-lactate in blood was similarly increased significantly from 5.1 +/- 5.0 mumols/liter at fast to 150.0 +/- 30.4 mumols/liter at 3 h after oral PD (P less than 0.001, n = 4). As was observed in the fasted blood of PD treated rabbits, D-lactate levels at fast and after saline ingestion in the control animals was found either absent or too low. Despite this increase in lactate, blood pH did not alter significantly when appropriate anticoagulant, i.e., heparin + 4-methylpyrazole, was employed.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of propane-diols on the intestinal uptake of nutrients and brush border membrane enzymes in the rat.

The effect on rats of oral doses (38.66 mM/kg body wt) of propane-1,2-diol (PD) administered daily for 10 (Group 1), 20 (Group 2), and 30 days (Group 3) was investigated. Weight gain was initially retarded (P less than 0.05) in Group 1, but was later reversed and elevated significantly (P less than 0.05) in Groups 2 and 3 as compared with their respective controls receiving an equal volume of saline. PD showed a tendency toward enhancing the activities of various enzymes involved in terminal digestion, with the significant effect exerted in few groups on sucrase (P less than 0.05), lactase (P less than 0.05), and gamma-glutamyl transpeptidase (P less than 0.05) when compared with the respective controls. Absorption of D-glucose, glycine, L-aspartic acid, L-lysine, and calcium was elevated and was especially significant in Groups 2 and 3 (P less than 0.001). The structural integrity of the jejunal surface was retained for the most part. A similar examination of the effects of PD was also carried out in vitro to ascertain whether PD itself or its metabolites are involved in its action. The in vitro effects of propane-1,2-diol were compared with those of the more toxic compound propane-1,3-diol. The former exerted greater inhibitory action on the activities of the disaccharidases. The degree of inhibition was in the order sucrase much greater than lactase greater than maltase. The kinetic data revealed that inhibition by 1,2-diol in native and detergent solubilized sucrase is noncompetitive, with Ki values in the range of 0.35-0.41 M. The two diols did not alter the nutrient transport in the brush border membrane vesicles. The present work on rats indicates that PD may influence the intestinal digestive and absorptive functions in vivo and that this in vivo effect of PD is different from that observed in vitro suggesting that the nutritional and toxicological effect of PD may be mediated by different mechanisms.

Effect of various doses of medroxyprogesterone acetate on intestinal functions in rats.

The dose relationship between medroxyprogesterone acetate (MPA), a long acting contraceptive, and rat intestinal digestive and absorptive functions has been investigated. The study revealed that the activities of brush border sucrase, lactase and leucine aminopeptidase were stimulated only at high doses, viz 70 mg/kg (180 mumol/kg) body weight and above, whereas the activity of alkaline phosphate was depressed at comparatively low dose (17.5 mg/kg; 45 mumol/kg body weight). This decrease was found to be significant (p less than 0.001) at all the doses tested. The inhibition in the intestinal uptake of calcium paralleled the decrease in alkaline phosphatase activity. Relatively high amount of MPA (140 mg/kg; 360 mumol/kg) was required to augment the uptake of glucose and amino acid. The results obtained do not indicate a close relationship between the dose of the drug and the extent of alteration in the rat intestinal digestive and absorptive functions. The study appears to confirm the association between brush border enzymes activities and uptake of nutrients in rat intestine.

Kinetics of oral propylene glycol-induced acute hyperlactatemia.

The kinetics of PD-induced HL in rat have been investigated. The data obtained indicated that PD was solely responsible for the elevation (1.83- to 4.01-fold) of blood lactate that was sustained long enough to affect considerably the normal physiological function of the system. The production of lactate increased as the dose of PD increased up to 38.66 mmole/kg, thereby obeying the Michaelis-Menten kinetics model that gave an apparent Km and Vmax as 7.14 mmole/kg and 7.50 mmole/liter/hr, respectively. The t1/2 elimination time ranged from 1.40 to 5.82 hr which followed apparent first-order kinetics. Pyrazole inhibited (Ki = 6 mumole/kg) the PD-induced HL competitively, suggesting that alcohol dehydrogenase might have played a regulatory role in the conversion of PD to lactate. The PD-induced HL in rat and the LA in human patients are two distinct biochemical entities; reasoning has been given to substantiate that HL is lower order LA. Evidence has been presented to show that PD is a suitable and effective potential agent for producing experimental HL in rat in preference to agents that are currently being used.