ABSTRACT
An excessive consumption of a diet rich in saturated fatty acids is a key factor in pathogenesis of cardiovascular diseases which are strictly connected with leptin imbalance in the vessels. However, whether vitamin E supplementation would influence leptin expression in aortic layers is still unknown. For 3 or 6 weeks male Wistar rats were fed a high-fat (20% w/w) diet with lard as dietary fat source with or without vitamin E supplementation (50 mg/100 g of diet). The 6-week intake of an atherogenic diet increased total cholesterol (TC) and high density lipoprotein cholesterol (HDL) plasma levels simultaneously lowering TC/HDL ratio (ANOVA p≤0.0001 for all three parameters). After longer period of feeding it was stated that leptin expression in all three aortic layers was enhanced (ANOVA p≤0.0001 for endothelium, tunica media and adventitia, respectively) with decreased leptin plasma concentration (ANOVA p≤0.0001). After both periods of feeding vitamin E supplementation caused an increase in plasma HDL content and a decrease of TC/HDL ratio. In the 3-week experiment vitamin E addition caused a decrease in leptin plasma levels (Fisher's test, 3L versus 3LE: p≤0.002) and an increase in leptin expression in all three aortic layers (Fisher's test, 3L versus 3LE p≤0.005, p≤0.01 and p≤0.05 respectively for endothelium, tunica media and adventitia). The contradictory results were observed in the 6-week experiment in which vitamin supplementation decreased leptin expression in the aortic endothelium (Fisher's test, 6L versus 6LE: p≤0.001) with lack of changes in the other two layers of the aorta and plasma. The study showed that vitamin E supplementation influenced leptin expression in aortic layers in rats fed atherogenic diet differently depending on the length of feeding period. It may suggest that vitamin E consumption plays an important role in the control of leptin status in the endothelium.
Subject(s)
Antioxidants/administration & dosage , Aorta/drug effects , Diet, High-Fat/adverse effects , Dietary Supplements , Leptin/metabolism , Vitamin E/administration & dosage , Adventitia/metabolism , Animals , Aorta/metabolism , Drug Administration Schedule , Endothelium, Vascular/metabolism , Leptin/blood , Male , Rats , Rats, Wistar , Tunica Media/metabolismABSTRACT
This study was designed to determine the effect of a potent subcutaneously injected acetylcholinesterase inhibitor, rivastigmine (6mg/animal), on the gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) release during inflammation induced by an intravenous lipopolysaccharide (LPS) (400ng/kg) injection in ewes during the follicular phase of the estrous cycle. The results are expressed as the mean values from -2 to -0.5h before and +1 to +3h after treatment. Rivastigmine decreased the acetylcholinesterase concentration in the blood plasma from 176.9±9.5 to 99.3±15.1µmol/min/ml. Endotoxin suppressed LH (5.4±0.6ng/ml) and GnRH (4.6±0.4pg/ml) release; however, the rivastigmine injection restored the LH concentration (7.8±0.8ng/ml) to the control value (7.8±0.7ng/ml) and stimulated GnRH release (7.6±0.8pg/ml) compared to the control (5.9±0.4pg/ml). Immune stress decreased expression of the GnRH gene and its receptor (GnRH-R) in the median eminence as well as LHß and GnRH-R in the pituitary. In the case of the GnRH and LHß genes, the suppressive effect of inflammation was negated by rivastigmine. LPS stimulated cortisol and prolactin release (71.1±14.7 and 217.1±8.0ng/ml) compared to the control group (9.0±5.4 and 21.3±3.5ng/ml). Rivastigmine also showed a moderating effect on cortisol and prolactin secretion (43.1±13.1 and 169.7±29.5ng/ml). The present study shows that LPS-induced decreases in GnRH and LH can be reduced by the AChE inhibitor. This action of the AChE inhibitor could result from the suppression of pro-inflammatory cytokine release and the attenuation of the stress response. However, a direct stimulatory effect of ACh on GnRH/LH secretion should also be considered.
Subject(s)
Cholinesterase Inhibitors/administration & dosage , Estrous Cycle/drug effects , Follicular Phase/drug effects , Gonadotropin-Releasing Hormone/metabolism , Luteinizing Hormone/metabolism , Phenylcarbamates/administration & dosage , Sheep, Domestic , Acetylcholinesterase/blood , Acetylcholinesterase/metabolism , Animals , Down-Regulation/drug effects , Estrous Cycle/blood , Estrous Cycle/metabolism , Female , Follicular Phase/blood , Follicular Phase/metabolism , Gene Expression/drug effects , Gonadotropin-Releasing Hormone/blood , Hypothalamus/drug effects , Hypothalamus/metabolism , Inflammation/blood , Inflammation/chemically induced , Inflammation/genetics , Injections, Subcutaneous , Lipopolysaccharides , Luteinizing Hormone/blood , Pituitary Gland/drug effects , Pituitary Gland/metabolism , Rivastigmine , Sheep, Domestic/blood , Sheep, Domestic/genetics , Sheep, Domestic/metabolism , Sheep, Domestic/physiologyABSTRACT
The present study was designed to determine the effect of subcutaneous rivastigmine treatment on IL-1ß expression and IL-1 type I receptor (IL-1R1) gene expression in the hypothalamic structures (preoptic area [POA], anterior hypothalamus [AHA], and medial basal hypothalamus [MBH]) of ewes after lipopolysaccharide (LPS) treatment. Endotoxin treatment increased (P ≤ 0.01) both IL-1ß and IL-1R1 gene expression in the POA, AHA, and MBH compared with the control group, whereas concomitant rivastigmine and LPS injection abolished this stimulatory effect. It was also found that LPS elevated (P ≤ 0.01) IL-1ß concentration in the hypothalamus (71.0 ± 2.3 pg/mg) compared with controls (16.1 ± 3.6 pg/mg). The simultaneous injection of LPS and rivastigmine did not increase IL-1ß concentration in the hypothalamus (24.6 ± 13.0 pg/mg). This central change in IL-1ß synthesis seems to be an effect of acetylcholinesterase (AChE) inhibition by rivastigmine, which decreases (P ≤ 0.01) the activity of this enzyme from 78.5 ± 15.0 µmol · min(-1) · g(-1) of total protein in the control and 68.8 ± 9.8 µmol · min(-1) · g(-1) of total protein in LPS-treated animals to 45.2 ± 5.6 µmol · min(-1) · g(-1) of total protein in the rivastigmine and LPS-treated group. Our study showed that rivastigmine could effectively reverse the stimulatory effect of immune stress induced by LPS injection on IL-1ß synthesis through a decrease in AChE activity in the hypothalamic area of sheep. Our results also proved that the cholinergic anti-inflammatory pathway could directly modulate the central response to endotoxin.
Subject(s)
Acetylcholinesterase/metabolism , Cholinesterase Inhibitors/pharmacology , Hypothalamus/drug effects , Hypothalamus/metabolism , Interleukin-1beta/biosynthesis , Phenylcarbamates/pharmacology , Sheep/metabolism , Acetylcholinesterase/analysis , Animals , Female , Gene Expression/drug effects , Hypothalamus/enzymology , Interleukin-1beta/genetics , Lipopolysaccharides/pharmacology , RNA, Messenger/chemistry , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction/veterinary , Receptors, Interleukin-1/biosynthesis , Receptors, Interleukin-1/genetics , Rivastigmine , Statistics, NonparametricABSTRACT
This study was designed to determine the effect of lavender and cinnamon oils on FtsZ gene expression in Staphylococcus aureus ATCC 29213. The cinnamon and lavender oils at least partially results from the inhibition of FtsZ transcription and disruption of cell division process at the level of the septum synthesis, what is similar to mechanisms of drug action used in anti-staphylococcal therapies. The presented results could be an important background for the further detailed research, which is needed to clarify the effect of essential oils on FtsZ synthesis at the posttranscriptional level and other stages of cell division process of S. aureus and other pathogenic bacteria.
Subject(s)
Bacterial Proteins/biosynthesis , Cytoskeletal Proteins/biosynthesis , Gene Expression Regulation, Bacterial/drug effects , Oils, Volatile/pharmacology , Plant Oils/pharmacology , Staphylococcus aureus/metabolism , LavandulaABSTRACT
This study was performed to determine the effect of intracerebroventricular (icv) injection of interleukin (IL)-1ß on the gene expression, translation and release of gonadotropin-releasing hormone (GnRH) and the GnRH receptor (GnRHR) gene expression in the hypothalamus of anestrous ewes. In the anterior pituitary gland (AP), the expression of genes encoding: GnRHR, ß subunits of luteinizing hormone (LH) and folliculotropic hormone (FSH) was determined as well as the effect of IL-1ß on pituitary gonadotropins release. The relative mRNA level was determined by real-time PCR, GnRH concentration in the cerebrospinal fluid (CSF) was assayed by ELISA and the plasma concentration of LH and FSH were determined by radioimmunoassay. Our results showed that icv injection of IL-1ß (10 or 50 µg/animal) decreased the GnRH mRNA level in the pre-optic area (POA) (35% and 40% respectively; p ≤ 0.01) and median eminence (ME) (75% and 70% respectively; p ≤ 0.01) and GnRHR gene expression in ME (55% and 50% respectively; p ≤ 0.01). A significant decrease in GnRHR mRNA level in the AP in the group treated with the 50 µg (60%; p ≤ 0.01) but not with the 10 µg dose was observed. The centrally administrated IL-1ß lowered also GnRH concentration in the CSF (60%; p ≤ 0.01) and reduced the intensity of GnRH translation in the POA (p ≤ 0.01). It was not found any effect of icv IL-1ß injection upon the release of LH and FSH. However, the central injection of IL-1ß strongly decreased the LHß mRNA level (41% and 50%; p ≤ 0.01; respectively) and FSHß mRNA in the case of the 50 µg dose (49%; p ≤ 0.01) in the pituitary of anestrous ewes. These results demonstrate that the central IL-1ß is an important modulator of the GnRH biosynthesis and release during immune/inflammatory challenge.
Subject(s)
Anestrus/physiology , Hypothalamus/drug effects , Interleukin-1beta/administration & dosage , Ovary/drug effects , Pituitary Gland/drug effects , Sheep/physiology , Animals , Female , Follicle Stimulating Hormone/blood , Follicle Stimulating Hormone, beta Subunit/genetics , Gene Expression/drug effects , Gonadotropin-Releasing Hormone/genetics , Gonadotropin-Releasing Hormone/metabolism , Gonadotropins, Pituitary/metabolism , Hypothalamus/metabolism , Injections, Intraventricular/veterinary , Luteinizing Hormone/blood , Luteinizing Hormone, beta Subunit/genetics , Ovary/metabolism , Pituitary Gland/metabolism , Pituitary Gland, Anterior/drug effects , Pituitary Gland, Anterior/metabolism , RNA, Messenger/analysis , Receptors, LHRH/geneticsABSTRACT
This study was designed to determine the effect of intravenous lipopolysaccharide (LPS) administration on the secretion of interleukin (IL)-1ß and IL-1 receptors (IL-1Rs) gene expression in the hypothalamus of anoestrous ewes. Gene expression of IL-1ß and its receptors was assayed by the real-time polymerase chain reaction. The expression of IL-1ß in the hypothalamus was detected using Western blot. Our results showed that IL-1ß mRNA is transcribed in the ovine hypothalamus. Lipopolysaccharide increased (p ≤ 0.01) the IL-1ß gene expression in the pre-optic area 2.4-fold, the anterior hypothalamus (AHA) 3.4-fold, the medial basal hypothalamus 3.7-fold and the medial eminence 3.9-fold. The pro-form and mature form of IL-1ß protein were found in the hypothalamus after endotoxin injection. In general, the endotoxin also increased more than two times (p ≤ 0.01) the expression of IL-1 receptor type I (IL-1R1) and type II (IL-1R2) genes in the hypothalamus, except the AHA, where the number of IL-1R2 mRNA was extremely low and not sufficient to the quantitative analysis. These results demonstrate that the peripheral immune/inflammatory challenge increases the IL-1ß expression in the hypothalamus. This endogenous IL-1ß seems to be involved in the modulation of processes which are regulated at the hypothalamic level. One of these processes could be a reproduction.