scholarly journals Endogenous and Exogenous Melatonin Exposure Attenuates Hepatic MT1 Melatonin Receptor Protein Expression in Rat

Antioxidants ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 408
Author(s):  
Alexander M. Mathes ◽  
Paul Heymann ◽  
Christian Ruf ◽  
Ragnar Huhn ◽  
Jochen Hinkelbein ◽  
...  
Keyword(s):  
Hemorrhagic Shock ◽  
Rat Liver ◽  
Quantitative Polymerase Chain Reaction ◽  
Melatonin Receptors ◽  
Male Rats ◽  
Receptor Protein ◽  
Male Rat ◽  
Enzyme Linked Immunosorbent Assay ◽  
Exogenous Melatonin ◽  
Plasma Melatonin

Melatonin receptors are highly relevant for the hepatoprotective effects of the pineal hormone melatonin after experimental hemorrhagic shock in rats. In this study, we sought to determine the spatial expression pattern and a putative regulation of two melatonin receptors, membrane bound type 1 and 2 (MT1 and MT2), in the liver of rats. In a male rat model (Sprague Dawley) of hemorrhage and resuscitation, we investigated the gene expression and protein of MT1 and MT2 in rat liver by utilizing real-time quantitative polymerase chain reaction, a western blot analysis, and immunohistochemistry. Plasma melatonin content was measured by an enzyme-linked immunosorbent assay. Male rats underwent hemorrhage and were resuscitated with shed blood and a Ringer’s solution (n = 8 per group). After 90 min of hemorrhage, animals were given vehicle, melatonin, or ramelteon (each 1.0 mg/kg intravenously). Sham-operated controls did not undergo hemorrhage but were treated likewise. Plasma melatonin was significantly increased in all groups treated with melatonin and also after hemorrhagic shock. Only MT1, but not the MT2 messenger ribonucleic acid (mRNA) and protein, was detected in the rat liver. The MT1 protein was located in pericentral fields of liver lobules in sham-operated animals. After hemorrhagic shock and treatment with melatonin or ramelteon, the hepatic MT1 protein amount was significantly attenuated in all groups compared to sham controls (50% reduction; p < 0.001). With respect to MT1 mRNA, no significant changes were observed between groups (p = 0.264). Our results indicate that both endogenous melatonin exposure from hemorrhagic shock, as well as exogenous melatonin and ramelteon exposure, may attenuate melatonin receptors in rat hepatocytes, possibly by means of desensitization.

scholarly journals Increased bioactivation of dihaloalkanes in rat liver due to induction of class Theta glutathione S-transferase T1-1

1998 ◽  
Vol 335 (3) ◽  
pp. 619-630 ◽  
Author(s):  
Philip J. SHERRATT ◽  
Margaret M. MANSON ◽  
Anne M. THOMSON ◽  
Erna A. M. HISSINK ◽  
Gordon E. NEAL ◽  
...  
Keyword(s):  
Western Blotting ◽  
Rat Liver ◽  
Female Rats ◽  
Male Rats ◽  
Male Rat ◽  
Female Rat ◽  
Glutathione S Transferase ◽  
Chemopreventive Agents ◽  
Cytoplasmic Staining ◽  
Potent Inducer

A characteristic feature of the class Theta glutathione S-transferase (GST) T1-1 is its ability to activate dichloromethane and dibromoethane by catalysing the formation of mutagenic conjugates. The level of the GSTT1 subunit within tissues is an important determinant of susceptibility to the carcinogenic effects of these dihaloalkanes. In the present study it is demonstrated that hepatic GST activity towards these compounds can be elevated significantly in female and male Fischer-344 rats by feeding these animals on diets supplemented with cancer chemopreventive agents. Immunoblotting experiments showed that increased activity towards the dihaloalkanes is associated with elevated levels of the GSTT1 subunit in rat liver. Sex-specific effects were observed in the induction of GSTT1 protein. Amongst the chemopreventive agents tested, indole-3-carbinol proved to be the most potent inducer of hepatic GSTT1 in male rats (6.2-fold), whereas coumarin was the most potent inducer of this subunit in the livers of female rats (3.5-fold). Phenobarbital showed significant induction of GSTT1 only in male rat liver and had little effect in female rat liver. Western blotting showed that class Alpha, Mu and Pi GST subunits are not co-ordinately induced with GSTT1, indicating that the expression of GSTT1 is determined, at least in part, by mechanisms distinct from those that regulate levels of other transferases. The increase in amount of hepatic GSTT1 protein was also reflected by an increase in the steady-state level of mRNA in response to treatment with chemopreventive agents and model inducers. Immunohistochemical detection of GSTT1 in rat liver supported the Western blotting data, but showed, in addition to cytoplasmic staining, significant nuclear localization of the enzyme in hepatocytes from some treated animals, including those fed on an oltipraz-containing diet. Significantly, the hepatic level of cytochrome P-450 2E1, an enzyme which offers a detoxification pathway for dihaloalkanes, was unchanged by the various inducing agents studied. It is concluded that the induction of GSTT1 by dietary components and its localization within cells are important factors that should be considered when assessing the risk dihaloalkanes pose to human health.

scholarly journals Exosomes Mediate Hippocampal and Cortical Neuronal Injury Induced by Hepatic Ischemia-Reperfusion Injury through Activating Pyroptosis in Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Limei Zhang ◽  
Hanyu Liu ◽  
Lili Jia ◽  
Jingshu Lyu ◽  
Ying Sun ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Neuronal Injury ◽  
Male Rats ◽  
Receptor Protein ◽  
Enzyme Linked Immunosorbent Assay ◽  
Hepatic Ischemia ◽  
Caspase 1 ◽  
Hepatic Ischemia Reperfusion

Background. The neuronal injury and cognitive dysfunction after liver transplantation have severe effects on the prognosis and life quality of patients. Accumulating evidence suggests that both exosomes and pyroptosis could participate in hepatic ischemia-reperfusion injury (HIRI) and play key roles in neuronal death. However, the link between exosomes and neuronal pyroptosis in HIRI awaits further investigation. Methods. After establishing the HIRI rat models, we primarily studied the role of pyroptosis in hippocampal and cortical neuron injury through detecting NOD-like receptor protein 3 (NLRP3), pro-caspase-1, cleaved-caspase-1, apoptosis-associated speck-like protein containing CARD (ASC), gasdermin D (GSDMD), interleukin-1beta (IL-1β), and interleukin-18 (IL-18) expressions with western blotting, immunohistochemical staining, and enzyme-linked immunosorbent assay (ELISA). Then, we intravenously injected normal male rats with exosomes isolated from the sera of HIRI-challenged rats and pretreated rats with MCC950, a specific inhibitor of NLRP3, and carried out the same assay. We also detected the levels of reactive oxygen species (ROS), superoxide dismutase (SOD), and malondialdehyde (MDA) in the hippocampal and cortical tissues. Results. The results indicated that NLRP3 inflammasome and caspase-1-dependent pyroptosis were activated in the hippocampus and cortex of HIRI rats. Furthermore, serum-derived exosomes from HIRI-challenged rats not only had the ability to cross the blood-brain barrier (BBB) but also had the similar effects on neuronal pyroptosis. Moreover, ROS and MDA productions were induced in the HIRI and exosome-challenged groups. In addition, to some degree, MCC950 could alleviate HIRI-mediated hippocampal and cortical neuronal pyroptosis. Conclusion. This study experimentally demonstrated that circulating exosomes play a critical role in HIRI-mediated hippocampal and cortical injury through regulating neuronal pyroptosis.

scholarly journals The Effect of Soy Milk on Mounting Latency, Mounting Frequency, and Reproductive Development in Male Wistar Rats (Rattus Norvegicus)

2021 ◽  
Vol 9 (B) ◽  
pp. 670-678
Author(s):  
Nurdiana Nurdiana ◽  
Pradnyawati Chania ◽  
Rifzi Nurvitasari ◽  
Azmiatun Nisa ◽  
Styan Wahyu Diana ◽  
...  
Keyword(s):  
Rattus Norvegicus ◽  
Wistar Rats ◽  
Reproductive Development ◽  
Normal Diet ◽  
Male Rats ◽  
Male Rat ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Soy Milk ◽  
Male Wistar Rats

AIM: This research aims to examine the effects of soy milk on mounting latency (ML), mounting frequency (MF), estrogen levels, androgen-binding protein (ABP) expression, and spermatogenesis in male rats (Rattus norvegicus). METHODS: Twenty-four male wistar rats (Rattus norvegicus) aged 4 weeks were divided into four groups. Control group (given a normal diet), P1; P2; P3 (given the normal diet and soy milk powder at doses of 7.1; 14.2; 21.3 g/KgBW/day, respectively) for 6 weeks. Observation of ML and MF were performed at 9 weeks 5 days of age, and rat surgery was performed at 10 weeks of age. Analysis of estrogen hormone levels was conducted by enzyme-linked immunosorbent assay (ELISA), ABP staining was using immunohistochemistry method, testicular spermatogenesis was observed using histopathological methods, and observation of spermatozoa was performed under the microscope.  RESULTS: The results showed no significant reduction of ML and MF, estrogen levels, and ABP expression (p ≤ 0.256; 0.865; 0.959, respectively) in male rat, but there was a significant decrease in the number, morphology, motility of spermatozoa, and testicular histophatology, (p ≤ 0.000, 0.003, 0.008, 0.000, respectively). CONCLUSION: The administrassion of soy milk in various doses (7.1;14.2;21.3 g/KgBW/day) in male Wistar rats (Rattus norvegicus) had showed significantly difference on histopathological evaluation using Johnson’s scoring system, sperm quantity and quality, while on mounting latency and frequency, estrogen levels, and ABP expressions did not show significantly difference between groups. That describe of isoflavone in soy milk can affect several aspects related to male endocrine and reproductive development.

scholarly journals Effect of exogenous melatonin and flaxseed oil on the expression state of MT1 receptors in rat skin under light deprivation

2021 ◽  
Vol 27 (2) ◽  
pp. 30-38
Author(s):  
I.S. Sobolevskaya ◽  
M.I. Krasnobaeva ◽  
O.D. Myadelets
Keyword(s):  
Flaxseed Oil ◽  
Hair Follicles ◽  
Melatonin Receptors ◽  
Male Rats ◽  
Target Cells ◽  
Special Role ◽  
Negative Consequences ◽  
Light Deprivation ◽  
Exogenous Melatonin ◽  
Corrective Effect

Most of the skin cells have their own autonomous functional circadian system, which is able to control physiological and biochemical processes in the general integument. A special role in these processes is assigned to the “clock” hormone of the pineal gland, melatonin, which acts on target cells through specific receptors (MT1, MT2, MT3 and RORα). Any disturbance of circadian rhythms can lead to rearrangements (disturbances) in the receptor apparatus of the cells of the general cover, which require a certain correction. Consequently, there is a need to search for effective and reliable drugs that will prevent the negative consequences caused by chronodestruction. In the present work, we studied the effectiveness of the effect of exogenous melatonin and flaxseed oil on the expression of MT1 receptors in the general coat of rats under light deprivation. An experimental study was carried out on 130 white outbred male rats (170-220 g), which were randomly divided into 5 groups: intact, light deprivation animals, light deprivation animals, which were injected intragastrically with flaxseed oil and melatonin. On days 7, 14 and 21, histological material was taken (fragments of the skin of the interscapular region of the back). For immunohistochemical studies, serial sections were stained using MTNR1A polyclonal antibodies. For morphometric data analysis, the Image Scope Color and ImageJ computer programs were used. All statistical data processing was performed using the Statistica 10.0 software. Differences were considered significant at a significance level of less than 0.01 (p <0.01). In the course of the experiment, it was found that light deprivation contributes to a change in the activity of expression of the MT1 melatonin receptors in the epidermis, sebaceous glands and hair follicles. Studies have shown that the administration of flaxseed oil, melatonin, and their combination to rats with desynchronosis is accompanied by the leveling of the adverse effect of desynchronosis on the studied parameters of MT1 receptors. The most pronounced corrective effect on the expression of MT1 receptors is observed with the introduction of exogenous melatonin on the 21st day of the experiment.

scholarly journals Intermittent hypoxia training blunts cerebrocortical presenilin 1 overexpression and amyloid-β accumulation in ethanol-withdrawn rats

2017 ◽  
Vol 313 (1) ◽  
pp. R10-R18 ◽  
Author(s):  
Myoung-Gwi Ryou ◽  
Robert T. Mallet ◽  
Daniel B. Metzger ◽  
Marianna E. Jung
Keyword(s):  
Messenger Rna ◽  
Quantitative Polymerase Chain Reaction ◽  
Amyloid Β ◽  
Protein Carbonyl ◽  
Ethanol Withdrawal ◽  
Male Rats ◽  
Presenilin 1 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Protein Carbonyl Content ◽  
Oxidative Protein Damage

Abrupt cessation of chronic alcohol consumption triggers signaling cascades that harm vulnerable brain regions and produce neurobehavioral deficits. We have demonstrated that a program of intermittent, normobaric hypoxia training (IHT) in rats prevents brain damage and neurobehavioral impairment resulting from abrupt ethanol withdrawal (EW). Moreover, EW induced expression of stress-activated protein kinase p38 and presenilin 1 (PS1), the catalytic subunit of γ-secretase that produces the neurotoxic amyloid-β (Aβ) peptides Aβ40 and Aβ42. We tested the hypotheses that 1) IHT limits EW-induced activation of the p38-PS1 axis, thereby attenuating γ-secretase activation and Aβ accumulation, and 2) EW disables heat shock protein 25 (HSP25), a p38 substrate, molecular chaperone, and antioxidant, and provokes protein carbonylation in a manner suppressed by IHT. Adult male rats completed two cycles of a 4-wk ethanol diet (6.5% wt/vol) and a 3-wk EW or an isocaloric, dextrin-based control diet. A 20-day IHT program (5–8 daily cycles of 5–10 min of 9.5–10% fractional inspired O2 + 4 min of 21% fractional inspired O2) was administered during the first EW phase. After the second EW phase, the brain was excised and the prefrontal cortex extracted. PS1, phosphorylated p38 (p-p38), and HSP25 were analyzed by immunoblot, PS1 messenger RNA by quantitative polymerase chain reaction, protein carbonyl content by spectrometry, and Aβ40 and Aβ42 contents by enzyme-linked immunosorbent assay. IHT attenuated the EW-associated increases in PS1, p-p38, Aβ40, Aβ42, and protein carbonyl contents, but not that of PS1 messenger RNA, while preserving functionally competent HSP25 dimers in EW rats. Collectively, these findings suggest that IHT may attenuate EW-induced γ-secretase overactivation by suppressing activation of the p38-PS1 axis and by preventing oxidative protein damage.

scholarly journals CIRCADIAN DYNAMICS OF OPTIC DENSITY OF MELATONIN RECEPTORS IN THE NEURONS OF HYPOTHALAMIC SUPRAOPTIC NUCLEUS IN RATS UNDER ALTERED PHOTOPERIOD

2019 ◽  
Vol 19 (3) ◽  
pp. 117-120
Author(s):  
K.V. Vlasova ◽  
R.Ye. Bulyk
Keyword(s):  
Circadian Rhythm ◽  
Pineal Gland ◽  
Supraoptic Nucleus ◽  
Light Stress ◽  
Melatonin Receptors ◽  
Male Rats ◽  
Endocrine Gland ◽  
Exogenous Melatonin ◽  
Protocol Standardization ◽  
Hypothalamic Supraoptic Nucleus

Introduction. Melatonin production is considerably suppressed by light and affects the ability to transfer daily rhythm information from the hypothalamus to other neural target sites and thus alters the expression of some biological rhythms. The hormone controls the state of the hypothalamic-pituitary system and endocrine gland activity through melatonin receptors (membrane, cytosolic and nuclear ones). In addition, using a mechanism of the feedback, it interferes with the activity of supraoptic nucleus of the hypothalamus, which regulates water-salt metabolism and responses to stress. Objective: to provide quantitative circadian characteristics of melatonin receptors density in the neurons of the hypothalamic supraoptic nucleus of rats being under light stimulation as well as the correction of changes after injecting exogenous melatonin. Material and methods. The experiments were conducted on 60 white mongrel mature male rats weighing 150 – 180 g. The test animals were divided into 3 parts each with 2 groups, kept under the conditions of standard light regime, hyperilluminated and the injection of exogenous melatonin and day-round lighting within 7 days. To perform immunohistochemical methods, we used polyclonal antibodies to melatonin 1A receptors produced by Abcam and streptavidin biotin visualization system LSAB2 (peroxidase mark + diaminobenzidine) produced by Chemicon International Inc. We adhered to protocol standardization of methods for all sections. Additional staining of nuclei was performed with Mayer hematoxylin. Results. The indices of optical density of specific melatonin 1A receptors of supraoptic neurocytes staining obtained in the intact group (at 02.00 AM- 0,488 ± 0,0024, at 02.00 P.M. - 0,464 ± 0,0023, p = 0.002) and in animals subjected to light stress (at 02.00 AM-0,295 ± 0, 0019, at 02.00 P.M.- 0,286 ± 0,0018, p = 0,012) had a probable value and were characterized by a clear diurnal periodicity. In the group of animals with pineal gland hypofunction modulation (at 02.00 A.M.- 0,216 ± 0,0017, at 02.00 P.M. - 0,214 ± 0,0021, p> 0,05). Conclusions The density of 1A melatonin receptors in rat’s hypothalamic supraoptic neurons are normally characterized by an accurate circadian rhythm. The highest density of receptors is observed at 02.00 AM, and at 02.00 PM it is significantly lower (p = 0.002). Immunohistochemical studies revealed that under inhibition of pineal gland activity the circadian rhythm of melatonin receptors density in neurons of supraoptic nuclei of the hypothalamus gets disturbed, which is characterized by an incredible difference of indices in the tested periods of the day.

scholarly journals Effect of age, gonadectomy and hypophysectomy on mitochondrial hydroxylation of vitamin D3 (cholecalciferol) and of 5β-cholestane-3α,7α,12α-triol in female and male rat liver

1988 ◽  
Vol 251 (2) ◽  
pp. 475-481 ◽  
Author(s):  
K Saarem ◽  
J I Pedersen
Keyword(s):  
Sex Hormones ◽  
Rat Liver ◽  
Vitamin D3 ◽  
Female Rats ◽  
Male Rats ◽  
Male Rat ◽  
Side Chain ◽  
Hydroxylase Activity ◽  
Testosterone Treatment ◽  
Alpha 7

In a previous study we found that liver mitochondrial side-chain hydroxylation of vitamin D3 (cholecalciferol) and of 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol was higher in female than in male rats [Saarem & Pedersen (1987) Biochem. J. 247, 73-78]. The present paper describes the effects of age, gonadectomy and hypophysectomy on these activities. The sex difference became manifest above the age of 7 weeks. Ovariectomy and/or injection of oestradiol valerate had no effect on the hydroxylase activities in adult females. Castration increased, and subsequent testosterone treatment decreased, the hydroxylase activities in adult males. Hypophysectomy had no effect in females, but increased the hydroxylase activities in males. Testosterone treatment had no effect in hypophysectomized females or males. Injection of oestradiol valerate had no effect on the hydroxylase activities in hypophysectomized females. In hypophysectomized males this treatment had no effect on the vitamin D3 25-hydroxylase activity, but decreased the C27-steroid 27-hydroxylase activity in males. Microsomal 1 alpha-hydroxyvitamin D3 25-hydroxylase activity was lower in females than in males in all age groups. Castration or hypophysectomy decreased the activity in male rats. It is concluded that, in adult female rats, the mitochondrial side-chain hydroxylation of vitamin D3 and of 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol is independent of sex hormones. In males these activities are regulated by influence of sex hormones on the hypophysis, probably by the presence of androgens in the neonatal period. Different effects on the two hydroxylases indicate the presence of at least two different cytochromes P-450 in rat liver mitochondria.

Androgen-linked control of rat liver carbonic anhydrase III

1983 ◽  
Vol 3 (5) ◽  
pp. 475-478 ◽  
Author(s):  
A. Shiels ◽  
S. Jeffery ◽  
I. R. Phillips ◽  
E. A. Shephard ◽  
C. A. Wilson ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Rat Liver ◽  
Marked Reduction ◽  
Male Rats ◽  
Testosterone Replacement ◽  
Male Rat ◽  
Carbonic Anhydrase Iii

The concentration of carbonic anhydrase IlI (CAIII) in male rat liver was found to be 30 times greater than that in the female. Castration of male rats led to marked reduction in liver CAIII concentrations which could be partially restored to control levels by testosterone replacement. Marked developmental and senescence changes in liver CAIII were also observed in male rats.

Use of Melatonin to Promote Sleep in Older People

2012 ◽  
Vol 7 (2) ◽  
pp. 90 ◽  
Author(s):  
Richard J Wurtman ◽  
Keyword(s):  
Side Effects ◽  
Older People ◽  
Low Dose ◽  
Sleep Onset ◽  
Melatonin Receptors ◽  
Older Americans ◽  
Exogenous Melatonin ◽  
Plasma Melatonin ◽  
The Brain

Many older Americans purchase the hormone melatonin and take it orally, nightly, to promote sleep onset and to help them fall back asleep after the frequent nocturnal awakenings associated with ageing. This need for exogenous melatonin reflects the fact that the progressive calcification of the human pineal diminishes the organ’s ability to secrete its hormone, so that instead of plasma melatonin levels rising normally by 10-fold or more around bedtime the rise may be only by twofold, or even less. The quantity of melatonin that most ageing people need to restore nocturnal plasma melatonin levels to what they are in youth – and, concurrently, to promote sleep – is tiny, only about 0.2–0.5 mg. However, this dosage is generally unavailable, so patients may take doses 10-fold greater, or more, producing side-effects (e.g., hypothermia; hypoprolactinaemia; morning grogginess) and ultimately desensitising melatonin receptors in the brain. The reasons why low-dose melatonin is generally unavailable are described and a strategy is proposed for enabling patients to consume the correct dosage even when preparations containing that dosage cannot be obtained.

Differences in cholesterol oxidation and biosynthesis in liver of male and female rats

1961 ◽  
Vol 200 (3) ◽  
pp. 519-522 ◽  
Author(s):  
David Kritchevsky ◽  
Ezra Staple ◽  
Joseph L. Rabinowitz ◽  
Michael W. Whitehouse
Keyword(s):  
Rat Liver ◽  
Sodium Acetate ◽  
Liver Mitochondria ◽  
Female Rats ◽  
Male Rats ◽  
Cholesterol Oxidation ◽  
Male Rat ◽  
Rat Liver Mitochondria ◽  
Oxidized Cholesterol ◽  
Liver Homogenates

Female rat liver mitochondria oxidized cholesterol-26-C14 and sodium pyruvate-2-C14 to C14O2 to a much greater extent (per mg N) than did male rat liver mitochondria. Mitochondrial preparations from livers of castrated, estrogenized or castrated-estrogenized male rats all oxidized cholesterol-26-C14 to a greater extent than did liver preparations from normal male rats. No differences were observed in the oxidation of sodium octanoate-1-C14. The serum and liver cholesterol levels of the feminized rats were higher than those of the intact males. Biosynthesis of cholesterol from sodium acetate-2-C14 by male rat liver homogenates was significantly lower than biosynthesis by liver homogenates from normal female rats or gonadectomized rats of both sexes. The rate of biosynthesis from mevalonic acid-2-C14 by liver homogenates from castrated male rats was much higher than in homogenates of oophorectomized females or intact males or females. Differences in sex or gonadectomy had no effect on biosynthesis of fatty acids from sodium acetate-2-C14.

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