Effects Of Short-term Oral Administration Research Articles

Sex-Specific Effects of Short-Term Oral Administration of Food-Grade Titanium Dioxide Nanoparticles in the Liver and Kidneys of Adult Rats.

Titanium dioxide (TiO2) nanomaterial is used in several items (implant materials, pills composition, cosmetics, etc.). Although TiO2 is no longer considered safe as a food additive, the general population is exposed daily through different routes, and information is lacking on some aspects of animal and human health. This study evaluated liver and kidney toxicity of food-grade TiO2 nanoparticles (NPs) (primary size < 25 nm) in male and female rats that were orally exposed for 5 days to 0, 1, and 2 mg/kg body weight per day (comparable with daily E171 consumption). Selected liver and kidney toxicity endpoints included serum biomarkers, histopathological analysis and expression of osteopontin (SPP1), vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), and neuropeptide Y (NPY). Although TiO2 NPs are known to affect the gastric mucosa, short-term exposure induced sex-specific effects: general toxicity parameters were predominantly altered in female rats, whereas the liver appeared to be more affected than the kidneys in male rats, which also showed overexpression of NPY and SPP1. In the kidneys, the TiO2 NP effects were quantitatively similar but qualitatively different in the two sexes. In conclusion, careful consideration should be paid to the presence of TiO2 NPs in other items that can lead to human exposure.

Effects of oral administration of trimethoprim-sulfamethoxazole on tear production in clinically normal guinea pigs.

To determine the effects of short-term oral administration of trimethoprim-sulfamethoxazole on tear production in clinically normal guinea pigs. Thirty-two healthy adult Abyssinian guinea pigs were used in this study. One day before the start of the trial, the pretreatment baseline phenol red thread test (PRTT) values were recorded. Sixteen guinea pigs in the treated group received 25 mg/kg trimethoprim-sulfamethoxazole orally twice a day for 14 days. The other sixteen guinea pigs were used as untreated controls and received a placebo during the study. All the ophthalmic tests were performed without chemical restraint. PRTT values were evaluated in both eyes of all the guinea pigs using a commercial PRTT strip of a single lot number on days 0 (baseline), 15, and 21 after starting the trial. The pretreatment baseline mean ± SD PRTT values for the treatment and control groups were 11.12 ± 3.82 mm/15 s and 11.93 ± 2.73 mm/15 s, respectively. After 14 days of drug administration, the mean ± SD PRTT values for the treatment and control groups were 10.87 ± 3.11 mm/15 s and 13.00 ± 2.47 mm/15 s, respectively. On Day 21, the mean ± SD PRTT values for the treatment and control groups were 12.62 ± 4.05 mm/15 s and 12.87 ± 2.99 mm/15 s, respectively. Significant decreases in the PRTT values, compared with the pretreatment baseline values, were not observed in the treatment group on Day 15 (P = 0.14) and Day 21 (P = 0.31). Trimethoprim-sulfamethoxazole did not decrease tear production in the guinea pigs in this study.

Effect of Lactobacillus paracasei ST11 on a nasal provocation test with grass pollen in allergic rhinitis

Probiotics have been associated with prevention and improvement of symptoms in atopic diseases such as atopic dermatitis. However, few studies exist that document their efficacy for upper airways allergies such as allergic rhinitis. To investigate the effect of short-term oral administration of Lactobacillus paracasei ST11 on a nasal provocation test (NPT) with grass pollen. Thirty-one adult volunteers with allergic rhinitis were enrolled in a randomized, double-blind, placebo-controlled study, based on two 4-week cross-over periods of product consumption (ST11-fermented milk vs. placebo), separated by a wash-out period of 6-8 weeks. Objective and subjective clinical parameters of NPT as well as systemic and nasal immunological parameters were compared between the two treatment periods (registration number: NCT 011 50 253). Subjects that received ST11-fermented milk had lower nasal congestion than subjects under placebo (visual analogical scale; P<0.05). Nasal pruritus followed the same trend. However, no significant change in combined nasal reaction threshold was observed between the two periods. IL-5 secretion by peripheral blood mononuclear cells and serum allergen-specific IgG4 were significantly lower in ST11-fermented milk group compared to placebo group. IL-8 and IL-10 secretion followed the same trend. Short-term treatment with ST11-fermented milk before NPT significantly improved a clinical marker of NPT (subjective nasal congestion) and down-regulated systemic immune markers (IL-5 from peripheral blood mononuclear cells and serum IgG4). These data strongly suggest that probiotics may down modulate key parameters of allergic rhinitis and warrant future evaluation in seasonal trials.

Effects of short-term oral administration of trimethoprim-sulfamethoxazole on Schirmer II tear test results in clinically normal rabbits

Fifteen New Zealand white rabbits were used in a study to determine whether oral administration of trimethoprim-sulfamethoxazole affects the rate of tear secretion in healthy rabbits. Ten rabbits received 40...

Oral administration of grape polyphenol extract ameliorates cerebral ischemia/reperfusion-induced neuronal damage and behavioral deficits in gerbils: comparison of pre- and post-ischemic administration

Oxidative stress has been regarded as an important underlying cause for the delayed neuronal death (DND) after cerebral ischemia. In this study, the effects of short-term oral administration of grape polyphenol extract (GPE) on ischemia/reperfusion (I/R) injury in a gerbil global ischemia model were determined. Ischemia was induced by occlusion of the common carotid arteries for 5 min. GPE (30 mg/ml)-containing formula or formula without GPE was administered daily via gavage for 4 days prior to and/or for 4 days after I/R. I/R resulted in hyperlocomotion, extensive DND, oxidative and fragmented DNA damage, and an increase in reactive astrocytes and microglial cells in the hippocampal CA1 region. GPE administration for 4 days prior to I/R and for 4 days after I/R attenuated DND, DNA damage and glial cell activation. However, neuroprotection was more pronounced when GPE was administered for 4 days after I/R than when administered for 4 days prior to I/R. GPE administration after I/R attenuated I/R-induced hyperlocomotion. These findings indicate that oral GPE intake may confer protection against I/R injury and emphasize that early intervention may be an effective therapeutic measure for ameliorating brain injury in stroke.

Effects of short-term oral administration of dietary marine oils in patients with inflammatory bowel disease and joint pain: A pilot study comparing seal oil and cod liver oil

Very long chain n-3 polyunsaturated fatty acids have modulating effects on inflammatory mechanisms. Seal and fish oils are rich in n-3 polyunsaturated fatty acids, and possibly therefore high doses of nasoduodenally administered seal oil rapidly relieved inflammatory bowel disease (IBD)-associated joint pain in two recent studies. In the present study, we compared the effects of short-term oral administration of seal oil and cod liver oil on IBD-related joint pain, leucotriene B(4) level, serum fatty acid profile and IBD activity. Thirty-eight patients with IBD-related joint pain were included in the study; 21 had Crohn's disease and 17 ulcerative colitis. Ten milliters of seal oil (n=18) or cod liver oil (n=20) was self-administered orally 3 times a day for 14 days before meals in a double-blind setting. There were no significant differences between the two intervention groups or between Crohn's disease and ulcerative colitis patients. There was a tendency toward improvement in several joint pain parameters after both seal oil and cod liver oil administration. Further, plasma leucotriene B(4) concentration, serum Sigma n-6 to Sigma n-3, and arachidonic acid (20:4n-6) to eicosapentaenoic acid (20:5n-3) ratios were similarly reduced after administration of seal oil and cod liver oil. No significant differences in the two treatment groups were seen; in both groups, the changes in several joint pain parameters, leucotriene B(4) level of plasma, and serum fatty acid profile were putatively favourable.

Wine polyphenols decrease blood pressure, improve NO vasodilatation, and induce gene expression.

The effects of short-term oral administration of red wine polyphenolic compounds on hemodynamic parameters and on vascular reactivity were investigated in rats. Endothelial function and vascular smooth muscle contractility were studied in association with the induction of gene expression in the vascular wall. Rats were treated daily for 7 days by intragastric administration of either 5% glucose or red wine polyphenolic compounds (20 mg/kg). Administration of these compounds produced a progressive decrease in systolic blood pressure, which became significantly different on day 4. Aortas from rats treated with red wine polyphenolic compounds displayed increased endothelium-dependent relaxation to acetylcholine that was related to increased endothelial NO activity and involved a mechanism sensitive to superoxide anion scavengers. However, no increase in whole-body oxidative stress has been observed in rats treated with red wine polyphenolic compounds, as shown by plasma glutathione assay. Also, in the aorta, red wine polyphenolic compounds increased the expression of cyclooxygenase-2 and increased the release of endothelial thromboxane A(2), which compensated for the extraendothelial NO-induced hyporeactivity in response to norepinephrine, resulting from enhanced inducible NO synthase expression. The present study provides evidence that short-term oral administration of red wine polyphenolic compounds produces a decrease in blood pressure in normotensive rats. This hemodynamic effect was associated with an enhanced endothelium-dependent relaxation and an induction of gene expression (of inducible NO synthase and cyclooxygenase-2) within the arterial wall, which together maintain unchanged agonist-induced contractility. These effects of red wine polyphenolic compounds may be a potential mechanism for preventing cardiovascular diseases.

Composition and aggregational forms of biliary lipids in human bile after short-term administration of Taurohyodeoxycholic acid

Introduction: Taurohyodeoxycholic acid (THDC), a new natural hydrophilic bile salt, dissolves human cholesterol gallstones in vitro and may be effective as a litholytic agent in vivo. We thus, investigated in man the effects of short-term oral administration of THDC on lipid composition and physical-chemical features of bile. Methods: Three patients with a nasobiliary drainage (positioned after sphincterotomy for bile duct stones removal) were given 3 g of THDC (1 g every 12 h). At time of the study patients had an intact entero-hepatic circulation and minimal signs of cholestasis. Bile was collected before each THDC administration, the last sample being obtained 14 h after the final THDC dose. All specimens were analyzed for individual bile salts (HPLC) and lipids. Biliary lipid carriers were separated by gel-chromatography on Superose-6 and analyzed by quasielastic light scattering (QLS) and electron microscopy (EM). Results: biliary THDC concentration represented 30.3, 27.2 and 29.2% of total bile salts, respectively. Lecithin and cholesterol concentration in bile did not change significantly during the study. In all bile lipids were almost exclusively eluted in a single gel-chromatographic peak, with an average molecular weight between 20 and 100 kDa QLS analysis of THDC-rich biles, demonstrated an average hydrodynamic diameter of this lipid-carrier of 300 nm. In THDC-free biles fractionated using the same conditions, the predominant lipid-carrier had an average hydrodynamic diameter of 250 nm. This difference in size was confirmed at EM. Conclusions: THDC is efficiently secreted in human bile, without causing changes in the concentration of biliary lipids. The latter, however, are assembled in structures larger than those found in THDC-free biles. The size and spherical appearance of these aggregates are consistent with those of large unilamellar vesicles or multilamellar structures.

The effects of dopamine blockade on the human flash electroretinogram.

Single-cell electrophysiologic studies have shown that dopamine modulates retinal activity, but its role in human retinal processing is unclear. We investigated the effects of short-term oral administration of dopaminergic receptor blocking agents on the flash electroretinogram in humans. Both chlorpromazine (25 and 50 mg) and fluphenazine (1 and 2 mg) significantly reduced electroretinogram b-wave amplitudes and also selectively reduced the amplitude of the first oscillatory potential. Implicit times were not altered. Metoclopramide (10 and 20 mg) had no effect on any electroretinographic variable. Our study indicates that dopamine receptor blocking agents with both D-1 and D-2 receptor affinities reduce the amplitude of the electroretinogram in humans.

Inhibition of angiotensin converting enzyme by ramipril in serum and tissue of man.

Studies in animal models have indicated that ramipril is a potent inhibitor of angiotensin converting enzyme (ACE) in serum and tissue. In our study, the normal range of ACE activity and the inhibitory effect of short-term oral administration of ramipril on ACE activity in human serum and tissue samples of renal cortex, heart and blood vessels were determined. ACE activity in the renal cortex (125.2 +/- 11.5 nmol/mg per min) was greater than 600 times that of the heart (0.20 +/- 0.01 nmol/mg per min), greater than 500 times that of the veins (0.23 +/- 0.09 nmol/mg per min) and greater than 150 times that of the arteries (0.80 +/- 0.23 nmol/mg per min). ACE activity in the renal cortex and arteries 2 h after last dosing was almost completely inhibited by ramipril whereas ACE activity in the veins and heart was inhibited to a lesser extent. Our results demonstrate in man, for the first time, an inhibition of tissue ACE following short-term oral treatment with an ACE inhibitor.

Doxepin and ethanol interaction

The effect of short-term oral administration of doxepin, a tricyclic antidepressant, on voluntary drinking of ethanol was studied in the rat as a function of sex. The effects of doxepin on ethanol and acetaldehyde metabolizing enzymes of hepatic and selected endocrine tissues were made in the presence and in the absence of ethanol. A reduction in voluntary ethanol intake was determined after the initial doxepin dose. This effect was not apparent during continued drug administration. Subsequently, a statistically insignificant reduction of ethanol drinking was noted 24 h and 72 h post-drug termination. Hepatic alcohol and aldehyde dehydrogenase were not altered from respective controls by doxepin in the presence and absence of ethanol. Epididymal and testicular adlehyde dehydrogenase were inhibited by doxepin from control in rats maintained on ethanol or water, respectively. The results suggest lack of adverse effect of doxepin on peripheral metabolism of alcohol metabolizing enzymes as compared to adverse interaction with acetaldehyde metabolizing enzyme in the endocrine tissues studied.

Determinants of the Pressor Effect of Phenylpropanolamine in Healthy Subjects

Phenylpropanolamine (PPA) is frequently used in over-the-counter diet aids and cold medicines, In view of concern about the safety of this sympathomimetic agent, we undertook a double-blind, multicenter clinical trial to determine the factors that influence the pressor effect of short-term oral administration of PPA in healthy individuals. Eight hundred eighty-one healthy individuals in four categories of body weight were randomized to receive placebo capsules three times per day (n = 286), a 75-mg sustained-release PPA hydrochloride preparation once per day (n = 296) followed by two doses of placebo capsules, or a 25-mg immediate-release PPA hydrochloride preparation three times per day (n = 299). The median age of the study population was 28 years, 56% were men, 73% were white, and 47% were in excess of 30% above their ideal body weight. Measurements of pulse rate and supine and standing blood pressure were made 11 times during the day of PPA administration. A statistically significant but clinically unimportant pressor effect for the short-term administration of PPA was observed. The effect occurred in the first 6 hours after administration and was greater in the sustained-release group. Significant independent determinants of the pressor effect of PPA were baseline diastolic blood pressure, baseline body weight, and treatment.

Modulatory effect on the pesticide captan on the immune response in rats and mice.

The effect of short-term oral administration of captan, [N-(trimethylthio)-4-cyclohexene-1,2-carboximide] on the immune response was studied in rats and mice. Animals were fed a diet with or without 0.3% (w/w) of captan for 7, 14, 21 and 42 days. The SRBC-antibody formation was depressed by about 70% in both species after 14 days of treatment. A release of inhibition occurred in mice at day 42. In a parallel manner, the lymphoblastic stimulation of splenic cells by PHA and by LPS was studied in captan-treated mice and their controls. The stimulation by PHA of splenic cells that were mainly T cells was clearly inhibited (45%) by day 14 of captan ingestion. Thereafter, the inhibition was only partially released until day 42. B cells, stimulated by LPS, presented a decrease in stimulation in captan-treated mice, during the first week of diet (20%). Then an important increase in the stimulation of these cells occurred at day 21 (85%) followed by a return to the normal value at day 42. These results pointed out a clear depressive effect of captan-diet on the immune response of the animals. The inhibition of SRBC-antibody formation during the first stage of the treatment may be correlated to the inhibitory effect of captan on T cells, which were cooperative with B cells for the expression of SRBC-antibody synthesis. These effects were obtained at a level of captan which was considerably lower than the toxic dose.

Effect of short-term oral administration of sunflower seed oil on the pattern of non-esterified fatty acids in human plasma

Effect of short-term oral administration of sunflower seed oil on the pattern of non-esterified fatty acids in human plasma