Effects Of Long-term Oral Administration Research Articles

Effect of long-term oral administration of the flavonoid quercetin on the antioxidant profile of young and adult reproductive rabbit does.

In industrialized farms, rabbit does undergo intensive production rhythms which overlap lactation and gestation, leading to a high energy mobilization and increasing oxidative stress. Accordingly, we hypothesize that administration of the flavonoid quercetin (QUR) may improve the antioxidant status of young and adult rabbit reproductive females. In this study, the effect of daily oral administration of 300 mg/kg QUR for 8 weeks was assessed on the antioxidant profile of 24 New Zealand × Californian rabbit does, assigned to 4 experimental groups: rearing young (8-16 weeks old) and adult does at the end of their reproductive life (12-14 months old, with at least 3-4 reproductive cycles) treated (YQ and AQ) or not (YC and AC) with QUR, respectively. Plasma glutathione (GSH), as well as serum superoxide dismutase (SOD) and malondialdehyde (MDA) were measured during the experimental period. To assess the health status of the animals, a physical examination was also performed. GSH plasma concentrations were significantly higher in young does at weeks 1 and 4, but not at week 8 of the experiment, irrespectively of QUR administration. An increase in GSH plasma concentration was observed during the 8-week experiment in both AQ and AC groups. Furthermore, QUR administration did not alter either SOD or MDA serum activity and concentration in any group during the experimental period. Physical examination revealed no differences between the experimental groups. In conclusion, under our experimental conditions, QUR did not modify the general clinical or the antioxidant profile of young and adult reproductive rabbit females.

Effect of Long-term Oral Administration of Different Dosages of Caffeine on Anesthetic Emerging Time

This paper aims to investigate the effect of prolonged oral ingestion of different doses of caffeine on anesthetic emergence time. In our experiment, eighteen male mice were selected and randomly divided into three groups of six mice, each according to the concentration of caffeine administered: a high-concentration caffeine group, a low-concentration caffeine group, and a blank control group. Mice were anesthetized with isoflurane and Zoletil 50, and the time of emergence was recorded for both anesthesia and the time of entry into anesthesia was recorded for Zoletil 50 anesthesia. Twenty-four hours after the anesthesia experiments, the mice were subjected to Morris water maze experiments, visual station experiments, hidden station experiments, and spatial exploration experiments. The results showed that both high-dose and low-dose coffee ig accelerated isoflurane and Zoletil 50 anesthesia emerging, with the high-dose being statistically more significant for the acceleration of anesthesia emerging. Prolonged oral coffee administration did not affect the time to enter anesthesia. Long-term oral coffee administration enhanced spatial exploration and spatial learning memory after anesthesia.

Effects of Long-Term Oral Administration of N-Palmitoylethanolamine in Subjects with Mild Cognitive Impairment: Study Protocol.

N-palmitoylethanolamine (PEA) plays a key role in preventing Aβ-mediated neuroinflammation and neurotoxicity in murine models. It has been demonstrated that PEA provides anti-neuroinflammatory, pain-relieving and neuroprotective actions even in humans. In this project, we aim to evaluate these anti-neuroinflammatory effects via the cognitive evaluation and biochemical analyses of a 12-month oral administration of PEA in subjects with mild cognitive impairment (MCI). Subjects with MCI will be randomized to placebo or PEA groups, and followed for another 6 months. Cognitive abilities and neurological inflammation will be examined at baseline and after treatment. The specific objectives of the project are to ascertain whether: (i) PEA influences the scores of the neuropsychological and behavioral evaluations after one-year treatment, comparing PEA-treated and placebo subjects in both MCI and control groups; (ii) PEA can change the inflammatory and neuronal damage markers of blood and urine in MCI subjects; and (iii) these changes correlate with the clinical scores of participating subjects.

RAGE-Dependent Effect of Exogenous Methylglyoxal Intake on Lung Biomechanics in Mice

Methylglyoxal (MG) is a known highly reactive dicarbonyl and precursor to free radicals and advanced glycation end-products (AGEs). It is discussed to be involved in tissue aging and in the pathogenesis of different degenerative diseases. The effect of long-term oral administration of MG, simulating dietary MG intake, on the lung biomechanics of wild type (WT) and receptor for advanced glycation end-products knockout (RAGE-KO) mice was studied using an ex vivo ventilation system starting at the age of 6 months and after feeding for 6 and 12 months with MG. Our results showed that MG was taken up in the circulation and efficiently excreted with urine. The amount of free urinary MG measured after 12 months of feeding was lowered. After 12 months feeding, a significant airway resistance increase accompanied by a decrease of the maximal inspiratory airflow was observed in WT animals. No effect of MG in lung function of RAGE-KO mice could be detected. Despite the evidence that MG entered the systemic circulation, no MG-derived AGE accumulation was detected in the lung lysates in dependency on MG-feeding. Our data indicate that the short-term feeding of MG has little effect in vivo. Only after long-term treatment was MG secretion reduced, leading to tissue impairment.

Effects of long-term oral administration of melatonin on tear production, intraocular pressure, and tear and serum melatonin concentrations in healthy dogs.

To evaluate the effects of long-term (30-day) oral administration of melatonin on tear production, intraocular pressure (IOP), and concentration of melatonin in the tears and serum of healthy dogs. 20 healthy sexually intact adult male dogs. 10 dogs were given melatonin (0.3 mg/kg, PO, q 24 h, administered in food at 9 am), and 10 dogs were given a placebo. Tear and serum melatonin concentrations, IOP, and tear production (determined with a Schirmer tear test) were recorded before (baseline) and 30 minutes, 3 hours, and 5 hours after administration of melatonin or the placebo on day 1 and 30 minutes after administration of melatonin or the placebo on days 8, 15, and 30. Data collection time had significant effects on tear production, IOP, and tear melatonin concentration but not on serum melatonin concentration. Treatment (melatonin vs placebo) had a significant effect on tear melatonin concentration, but not on tear production, IOP, or serum melatonin concentration; however, tear melatonin concentration was significantly different between groups only 30 minutes after administration on day 1 and not at other times. In healthy dogs, long-term administration of melatonin at a dosage of 0.3 mg/kg, PO, every 24 hours did not have any clinically important effects on tear production, IOP, or serum or tear melatonin concentrations.

Biochemical changes associated with the administration of aqueous pulp extract of Irvingia gabonensis fruit on adult male Wistar rats

Biochemical changes associated with the administration of aqueous pulp extract of Irvingia gabonensis fruit on adult male Wistar rats

Effects of long-term oral administration of silver nanoparticles on the cognitive functions of mammals

Introduction. Since the beginning of the XXI century, silver nanoparticles have been widely used in various industries, medicine and pharmaceuticals due to their pronounced antibacterial, antiviral and fungicidal properties. In connection with such a high demand for the use of silver nanoparticles, it is very important to understand the associated potential risks from their use. Materials and methods. In the course of the work, there has been a study of the effects of the long-term oral administration of a commercially produced dietary supplement based on silver nanoparticles with a size of 34 nm and stabilized with polyvinylpyrrolidone in an amount of 50 μg/day/animal on the cognitive functions of C57Bl/6 mice, as well as their accumulation in the brain by the method of instrumental neutron activation analysis. The dietary supplement used is recommended for people as a treatment for gastrointestinal infections. Results. It was found that after 180 days of administration, silver nanoparticles impair long-term contextual memory, and over time, the content of silver in the brain increases. Conclusion. Presumably impaired cognitive function with accumulation of silver in the brains of mice. This poses the risk of prolonged oral use of the silver nanoparticles.

Effects of long-term oral administration of β-blocker on septic myocardial injury and prognosis

To investigate the effect of long-term oral administration of β-blocker on septic myocardial injury and prognosis. A retrospective study was conducted. Patients who were admitted to the emergency intensive care unit (EICU) and intensive care unit (ICU) of Tongde Hospital of Zhejiang Province from January 2015 to June 2020 were enrolled. A total of 289 patients who met the criteria of myocardial injury induced by sepsis were included in the analysis. Among them, 187 patients who had never taken β-blocker within 3 months before diagnosis were divided in the non-β-blocker group, and 102 patients who took β-blocker daily for more than 3 months before diagnosis were in the β-blocker group. The physiological and biochemical characteristics were compared between the two groups, including heart rate, mean arterial pressure (MAP) at the time of diagnosis, cardiac troponin I (cTnI), brain natriuretic peptide (BNP), MB isoenzyme of creatine kinase (CK-MB), blood lactic acid (Lac), central venous oxygen saturation (ScvO2), sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation II (APACHE II) score within 24 hours of diagnosis, left ventricular ejection fraction (LVEF), early and late mitral orifice diastolic peak flow velocity ratio (E/A), utilization rate of vasoactive drugs during hospitalization and 28-day mortality. The heart rate in the β-blocker group at the time of diagnosis was significantly lower than that in the non-β-blocker group (bpm: 107±8 vs. 110±7, P < 0.01), and the levels of cTnI and BNP within 24 hours of diagnosis were significantly lower than those in the non-β-blocker group [cTnI (μg/L): 0.191 (0.220) vs. 0.291 (0.300), BNP (ng/L): 627 (133) vs. 690 (201), both P < 0.05]. However, there were no significant differences in MAP, CK-MB, Lac, ScvO2, SOFA score, APACHE II score, LVEF, E/A, vasoactive drug utilization rate, and 28-day mortality between the β-blocker and non-β-blocker groups [MAP (mmHg, 1 mmHg = 0.133 kPa): 70.6±3.9 vs. 69.9±3.8, CK-MB (μg/L): 4.24 (3.33) vs. 4.32 (3.13), Lac (mmol/L): 3.50 (1.80) vs. 3.50 (1.90), ScvO2: 0.729±0.032 vs. 0.735±0.041, SOFA score: 7.74±2.34 vs. 7.25±2.23, APACHE II score: 17.19±5.13 vs. 18.27±6.12, LVEF: 0.567±0.058 vs. 0.557±0.051, E/A: 0.71 (0.20) vs. 0.69 (0.20), vasoactive drug utilization rate: 60.8% (62/102) vs. 56.7% (106/187), 28-day mortality: 23.5% (24/102) vs. 25.7% (48/187), all P > 0.05]. Long-term oral administration of β-blocker reduce myocardial injury in septic patients, and has no effect on disease severity and prognosis.

Histopathological Changes in Liver Tissue after repeated administrations of an Intermediate Dose of Coenzyme Q10 to Wistar Rats

Coenzyme Q10 (Co-Q10) or ubiquinone plays an important role in the cellular metabolism. The safety profile of ubiquinone as a dietary supplement has been assessed in few sub-chronic toxicity studies. The aim of this study was to evaluate the possible hepatotoxic effect of long-term oral administration of an intermediate oral dose of Co-Q10 in experimental animals. Fifteen Wistar rats were treated with 300mg/kg daily oral doses of Co-Q10 using forced oral feeding for six weeks. Additional 5 healthy rats represented the control group for comparison. All rats were euthanized at the end of the 6th week. Then H and E stained histological sections of rats’ livers revealed vacuolation of hepatocytes, an increase in the diffusion of macrophages and the formation of microgranuloma most probably indicating a drug-induced injury. In conclusion, this study adds evidence supporting the potential hepatotoxic actions resulting from repeated administration of intermediate oral dose of Co-Q10 especially on the long-term.

Oral delivery of xenon for cardiovascular protection

Cardiac hypertrophy often causes impairment of cardiac function. Xenon (Xe), a naturally occurring noble gas, is known to provide neurological and myocardial protection without side effects. The conventional method of Xe delivery by inhalation is not feasible on a chronic basis. We have developed an orally deliverable, effective Xe formulation for long-term administration. We employed 2-hydroxypropyl)-β-cyclodextrin (HPCD), which was dissolved in water to increase the Xe concentration in solution. The beneficial effects of long-term oral administration of Xe-enriched solutions on cardiovascular function were evaluated in vivo. HPCD increased Xe solubility from 0.22 mM to 0.67 mM (3.8-fold). Aged ApoE knockout mice fed high-fat diet for 6 weeks developed hypertension, and myocardial hypertrophy with impaired cardiac function. Oral Xe prevented this ischemic damage, preserving normal blood pressure, while maintaining normal left ventricular mass and wall thickness. This novel formulation allows for gastrointestinal delivery and cardiovascular stabilization.

Long-term administration of Aspalathus linearis infusion affects spatial memory of adult Sprague-Dawley male rats as well as increases their striatal dopamine content

Ethnopharmacological relevanceEveryday use of the herbal tea rooibos, produced from Aspalathus linearis (Brum.f) Dahlg. (Fabaceae) is customary in South Africa, a continuation of its historical use by indigenous people. Although evidence of its traditional indications is anecdotal, rooibos tea is regarded as a general health tea. Aims of the studyAvailable contemporary research indicates to broad cell protective activity of rooibos focusing on its antioxidative, anti-inflammatory, anti-hyperglycaemic and antithrombotic features affecting metabolic syndrome, cardiovascular risk and neuroprotection. Nevertheless little is known about its impact on brain functions. The present experiment aimed to evaluate the possible behavioural and neurochemical effects of long-term oral administration of “fermented”” rooibos herbal tea (FRHT) infusions to adult male Sprague-Dawley rats. Materials and methodsInfusions, prepared using 1, 2 and 4 g of “fermented”” (oxidised) A. linearis leaves for 100 ml of hot water, were characterised in terms of flavonoid content by ultra-high and high performance liquid chromatography (UHPLC-qTOF-MS, HPLC-DAD) and administered to rats as sole drinking fluid for 12 weeks. Spatial memory behaviour was assessed in a modified version of the Morris water maze. Dopamine, noradrenaline, serotonin and their metabolite levels (DOPAC, 3-MT, HVA, MHPG, 5-HIAA) were quantified in prefrontal cortex, hippocampus and striatum by HPLC-ECD. Body weight and blood glucose level were additionally estimated. ResultsAll FRHT-treated rats showed improvement of long-term spatial memory defined as increased number of crossings over the previous platform position in SE quadrant of the water maze. It was not accompanied by excessive motor activity. Striatal dopamine and its metabolite 3-MT (3-methoxytyramine) levels were increased in treated rats. There were no differences in body weight gain between control and treated animals but blood glucose level was significantly lower in the latter ones. ConclusionThe improvement of long-term memory in FRHT-treated rats and stimulating impact of FRHT on their dopaminergic striatal transmission support the wellness enhancing effect of rooibos tea, contributing to a better understanding of the neurological background of traditional habitual consumption of this herbal tea.

Effect of Long-term Administration of Oral Magnesium Sulfate and Insulin to Reduce Streptozotocin-Induced Hyperglycemia in Rats: the Role of Akt2 and IRS1 Gene Expressions.

The effects of long-term oral administration of magnesium sulfate and insulin on hyperglycemia were investigated using Akt2 and IRS1 gene expression methods in streptozotocin-induced diabetic rats. Fifty rats were randomly divided into five experimental groups: 1, non-diabetic control (NDC); 2, Mg2+-treated non-diabetic control (Mg-NDC); 3, chronic diabetic (CD); 4, Mg2+-treated chronic diabetic (Mg-CD); and 5, insulin-treated chronic diabetic (Ins-CD). Streptozotocin was used to induce diabetes. The Mg-CD and Mg-NDC groups received 10g/l of MgSO4 added to drinking water. The Ins-CD group received 2.5U/kg of insulin twice a day. Blood glucose level and body weight were measured every week. The intraperitoneal glucose tolerance test (IPGTT) was performed after 16weeks. MgSO4 administration improved the blood glucose level and IPGTT. It also increased Akt2 and IRS1 genes as well as protein expression. Insulin lowered the blood glucose level and increased IRS1 gene and protein expression, but did not affect Akt2 gene and protein expression. Glucose reduction after Mg therapy may be mediated, at least partially, via IRS1 and Akt2 genes and protein stimulation. In insulin-treated rats, insulin resistance was not significant due to the absence of Akt2 gene expression.

Long-term administration of pDC stimulative lactic acid bacteria, Lactococcus lactis strain Plasma, prevents immune-senescence and decelerates individual senescence.

Aging is accompanied by the decline in immune function, resulting in increasing susceptibility to infectious diseases and tumorigenesis. In our previous reports, we showed that Lactococcus lactis subsp. lactis strain Plasma (LC-Plasma) stimulated plasmacytoid dendritic cells (pDCs), which play an important role in viral infection, and oral administration of LC-Plasma showed prophylactic effects against viral infection both in mice and humans. However, the effects of long-term administration of LC-Plasma are not known. In this study, we investigated the effect of long-term oral administration of LC-Plasma on IFN-α induction activity and individual senescence in the senescence-accelerated mice strains Prone 1 (SAMP1) and Prone 10 (SAMP10). LC-Plasma administration promoted IFN-α induction activity and increased the naïve T cell ratio in SAMP1 mice. In SAMP10 mice, in addition to preventing a decrease in the naïve T cell ratio, aging-associated skin thinning was suppressed histologically and the expression of representative tight junction genes, such as Claudin-1 and Zo-1, was increased. Furthermore, age-related muscle weight loss tended to be suppressed in the LC-Plasma group and expression of the muscle degeneration gene FoxO-1 was significantly suppressed. Related to these phenotypes, the senescence score in the LC-Plasma group was significantly decreased at 47 weeks of age compared with that in the control group. Taken together, long-term oral administration of LC-Plasma could prevent immune-senescence and other senescence phenotypes at the organ level. Therefore, LC-Plasma is suggested to be a useful functional food material for decelerating individual senescence.

Long-term administration of pDC-Stimulative Lactococcus lactis strain decelerates senescence and prolongs the lifespan of mice

The decline in immune function caused by aging increases the risk of infectious diseases, tumorigeneses and chronic inflammation, resulting in accelerating senescence. We previously reported a lactic acid bacteria, Lactococcus lactis strain Plasma (synonym of Lactococcus lactis subsp. lactis JCM 5805, Lc-Plasma), that stimulates plasmacytoid dendritic cells (pDCs), which play a crucial role in phylaxis from viral infection. In this study, we investigated the anti-aging effects of long-term oral administration of Lc-Plasma in a senescence-accelerated mouse strain, SAMP6. Mice given Lc-Plasma showed a significant improvement in survival rate at 82 weeks and a decreased senescence score as compared with control mice throughout this study. Anatomic analysis at 82 weeks revealed that the frequency of altered hepatocellular foci was significantly lower, and the incidence of other pathological findings in the liver and lungs tended to be lower in Lc-Plasma mice than in control mice. Transcription level of the IL-1β gene in lungs also tended to be lower in Lc-Plasma mice. Furthermore, the thinning of skin and age-related decrease in muscle mass were also significantly suppressed in the Lc-Plasma group as compared with the control group. Consistent with these phenotypic features, pDCs activity was significantly higher in Lc-Plasma mice than in control mice. In conclusion, long-term administration of Lc-Plasma can decelerate senescence and prolong lifespan via maintenance of the immune system due to activation of pDCs.

Effects of long-term oral administration of methimazole on femur and tibia properties in male Wistar rats

Physiological concentrations of thyroid hormones are crucial for skeletal growth and development, physiological bone turnover and bone homeostasis maintenance. Methimazole (1-methyl-2-mercaptoimidazole) is an antithyroid drug used for the treatment of the hyperthyroidism in humans and animals. The aim of the study was to determine effects of long-term oral methimazole treatment in male Wistar rats on biochemical bone metabolism markers, as well as morphological, geometric, densitometric and mechanical properties of femur and tibia. Experimental rats were subjected to 90-day-long oral treatment with 0.05% water solution of methimazole and were kept under identical environmental conditions and received the same diet ad libitum as the control group. Serum concentration of osteocalcin (OC) and C-terminal telopeptides of type I collagen (CTX-I) was determined. Femur and tibia were evaluated using quantitative computed tomography (QCT), peripheral QCT (pQCT) and three-point bending test. Final body weight of the experimental group was significantly decreased by 30% (P=0.01). Methimazole treatment significantly decreased serum OC concentration by 21% (P=0.02) and increased CTX-I concentration by 17% (P=0.06). Methimazole decreased morphological, geometric and densitometric parameters of femur and tibia in rats. Mechanical evaluation of bones has shown significantly decreased maximum elastic strength and ultimate strength of femur in rats treated with methimazole by 36% and 40% when compared to the control group (P<0.05). In conclusion, this study has shown that long-term treatment with methimazole inhibits bone formation and accelerates bone resorption processes. The observed negative effects of methimazole treatment on body weight gain and skeletal properties may be considered as additional possible side effects in living organisms to those reported in the previous studies. It may be suggested that long-term antithyroid treatment should be combined with prevention of the negative effects of methimazole on bone tissue and whole body metabolism.

Berberine action targets and its absorption behavior：how to use old drug for new mechanisms

A variety of pharmacological effects of berberine (BBR) are constantly being discovered with the deepening of BBR research. What followed is how to rationally use the drug according to these new pharmacological effects. Because of some cardiac toxicity and poor oral absorption, conflicts may arise between improving the bioavailability and controlling the toxicity of BBR. Meanwhile some new therapeutic uses of BBR, such as hypolipidemia, hypoglycemia as well as prevention and treatment of neurodegenerative diseases, need long-termoral administration, thereby may lead to alteration of intestinal flora and potentially affect body's other physiological functions. Based on the stated targets of BBR and related pharmaceutical properties, comprehensive analysis of these issues was conducted in this study. Some suggestions were presented below：the effect of long-term oral administration on body function, especially the intestinal flora, needs to be further investigated; risks shall be considered in changing the composition of the formulation to improve the absorption rate of oral administration; for the medication with higher concentration demand (such as anti-cancer), targeted drug-delivery is worthy to be considered.

Passiflora incarnata L. Improves Spatial Memory, Reduces Stress, and Affects Neurotransmission in Rats.

Passiflora incarnata L. has been used as a medicinal plant in South America and Europe since the 16th century. Previous pharmacological studies focused mainly on the plant's sedative, anxiolytic, and anticonvulsant effects on the central nervous system and its supporting role in the treatment of addiction. The aim of the present study was to evaluate the behavioral and neurochemical effects of long-term oral administration of P. incarnata. The passionflower extract (30, 100, or 300 mg/kg body weight/day) was given to 4-week-old male Wistar rats via their drinking water. Tests were conducted after 7 weeks of treatment. Spatial memory was assessed in a water maze, and the levels of amino acids, monoamines, and their metabolites were evaluated in select brain regions by high performance liquid chromatography (HPLC). We observed reduced anxiety and dose-dependent improvement of memory in rats given passionflower compared to the control group. In addition, hippocampal glutamic acid and cortical serotonin content were depleted, with increased levels of metabolites and increased turnover. Thus, our results partially confirmed the proposed mechanism of action of P. incarnata involving GABAA receptors. Copyright © 2016 John Wiley & Sons, Ltd.

Melatonin attenuates impairments of structural hippocampal neuroplasticity in OXYS rats during active progression of Alzheimer's disease-like pathology.

Translational research on Alzheimer's disease (AD) has often focused on reducing the high cerebral levels of amyloid-β (Aβ) as a key characteristic of AD pathogenesis. There is, however, a growing body of evidence that synaptic dysfunction may be crucial for the development of the most common (sporadic) form of AD. The applicability of melatonin (mainly produced by the pineal gland) to the treatment of AD is actively evaluated, but usually, such studies are based on animal models of early-onset AD, which is responsible for only ~5% of AD cases. We have shown previously that in OXYS rats (an established model of sporadic AD), accumulation of toxic forms of Aβ in the brain occurs later than does the development of signs of neurodegenerative changes and synaptic failure. In this regard, recently, we uncovered beneficial neuroprotective effects of melatonin (prophylactic dietary supplementation) in OXYS rats. Our aim here was to evaluate, starting at the age of active progression of AD-like pathology in OXYS rats, the effects of long-term oral administration of melatonin on the structure of synapses and on neuronal and glial cells of the hippocampus. Melatonin significantly increased hippocampal synaptic density and the number of excitatory synapses, decreased the number of inhibitory synapses, and upregulated pre- and postsynaptic proteins (synapsin I and PSD-95, respectively). Furthermore, melatonin improved the ultrastructure of neuronal and glial cells and reduced glial density. Based on our past and present results, the repair of neuroplasticity by melatonin is a promising strategy against AD.

Effect of long-term oral administration of a low dosage of clenbuterol on body fat percentage in working and nonworking adult horses.

To determine the anabolic and lipolytic effects of a low dosage of clenbuterol administered orally in working and nonworking equids. 8 nonworking horses and 47 polo ponies in active training. Each polo pony continued training and received either clenbuterol (0.8 μg/kg) or an equal volume of corn syrup (placebo) orally twice daily for 21 days, and then was evaluated for another 21-day period. Nonworking horses received clenbuterol or placebo at the same dosage for 21 days in a crossover trial (2 treatments/horse). For working and nonworking horses, percentage body fat (PBF) was estimated before treatment and then 2 and 3 times/wk, respectively. Body weight was measured at intervals. Full data sets were not available for 8 working horses. For working horses, a significant treatment effect of clenbuterol was detected by day 3 and continued through the last day of treatment; at day 21, the mean change in PBF from baseline following clenbuterol or placebo treatment was -0.80% (representing a 12% decrease in PBF) and -0.32%, respectively. By day 32 through 42 (without treatment), PBF change did not differ between groups. When treated with clenbuterol, the nonworking horses had a similar mean change in PBF from baseline from day 6 onward, which peaked at -0.75% on day 18 (an 8% decrease in PBF). Time and treatment had no significant effect on body weight in either experiment. Among the study equids, long-term low-dose clenbuterol administration resulted in significant decreases in body fat with no loss in body weight.

Effect of long-term administration of arachidonic acid on n-3 fatty acid deficient mice

The effect of long-term oral administration of arachidonic acid (ARA, 240mg/kg/day) on brain function was assessed for mice maintained on an n-3 fatty acid adequate or deficient diet. The administration of ARA for 13 weeks resulted in an elevation of spontaneous motor activity, or the tendency thereof, in both the n-3 fatty acid adequate and deficient groups. However, the n-3 fatty acid deficient mice that were administered with ARA revealed marked deterioration in motor function in a motor coordination test. In the experiment to investigate changes over time, the motor activity of the ARA-administered group continued to increase mildly in n-3 deficient mice, although that of the control group showed a decrease involving habituation for both diet groups from the second week. The fatty acid composition of the brain at the end of the behavioral experiments indicated an increase in the levels of ARA and other n-6 fatty acids, as well as a decrease in the levels of docosahexaenoic acid. These results suggest that long-term administration of ARA causes an increase of futile spontaneous motor activity and the diminution of motor function by aggravation of n-3 fatty acid deficiency.