Showing papers on "Pinealectomy published in 2022"

Influence of Pinealectomy and Long-term Melatonin Administration on Inflammation and Oxidative Stress in Experimental Gouty Arthritis

Abstract: Gout is an inflammatory arthritis characterized by the deposition of monosodium urate (MSU) crystals in the joints or soft tissue. MSU crystals are potent inflammation inducers. Melatonin (MLT) is a powerful endogenous anti-inflammatory agent and effective in reducing cellular damage. In the present study, possible underlying mechanisms associated with anti-inflammatory and antioxidative effects were investigated in rats with gouty arthritis and melatonin deprivation treated with MLT. Fifty-six rats were divided into seven groups: control, sham control, pinealectomy (PNX), MSU (on the 30th day, single-dose 20 mg/ml, intraperitoneal), MSU + MLT (10 mg/kg/day for 30 days, intraperitoneal), MSU + PINX and MSU + PINX + MLT. PNX procedure was performed on the first day of the study. As compared to the controls, the results showed that MSU administration caused significant increases in oxidative stress parameters (malondialdehyde and total oxidant status). Besides, significant decreases in antioxidant defense systems (glutathione, superoxide dismutase and total antioxidant status) were observed. A statistically significant increase was found in the mean histopathological damage score in the groups that received MSU injection. It was found that histopathological changes were significantly reduced in the MSU + MLT group given MLT. In our study, it was determined that many histopathological changes, as well as swelling and temperature increase in the joint, which are markers of inflammation, were significantly reduced with MLT supplementation. These results suggest that melatonin ameliorates MSU-induced gout in the rat through inhibition of oxidative stress and proinflammatory cytokine production.

Impact of Melatonin Deficit on Emotional Status and Oxidative Stress-Induced Changes in Sphingomyelin and Cholesterol Level in Young Adult, Mature, and Aged Rats

Abstract: The pineal gland regulates the aging process via the hormone melatonin. The present report aims to evaluate the effect of pinealectomy (pin) on behavioral and oxidative stress-induced alterations in cholesterol and sphingomyelin (SM) levels in young adult, mature and aging rats. Sham and pin rats aged 3, 14 and 18 months were tested in behavioral tests for motor activity, anxiety, and depression. The ELISA test explored oxidative stress parameters and SM in the hippocampus, while total cholesterol was measured in serum via a commercial autoanalyzer. Mature and aged sham rats showed low motor activity and increased anxiety compared to the youngest rats. Pinealectomy affected emotional responses, induced depressive-like behavior, and elevated cholesterol levels in the youngest rats. However, removal of the pineal gland enhanced oxidative stress by diminishing antioxidant capacity and increasing the MDA level, and decreased SM level in the hippocampus of 14-month-old rats. Our findings suggest that young adult rats are vulnerable to emotional disturbance and changes in cholesterol levels resulting from melatonin deficiency. In contrast, mature rats with pinealectomy are exposed to an oxidative stress-induced decrease in SM levels in the hippocampus.

Metabolic footprint in young, middle-aged and elderly rats with melatonin deficit

Abstract: The pineal gland is suggested to be an essential area involved in the programming of fertility, growth, aging, and death of mammals via the released hormone melatonin.The present study aimed to ascertain the effect of melatonin deficit on several physiological and metabolic parameters, closely associated with the aging process, at certain stages of ontogenesis. Sham and rats with pinealectomy, operated at ages 3, 14, and 18-months, respectively, were tested two months later. Sham rats demonstrated an age-related decline of muscle strength, exercise endurance, motor activity, food intake, calorimetric parameters, and impaired lipid profile. Pinealectomy reduced the maximal time to exhaustion and body weight gain while diminished motor activity, food intake, O2 consumption, CO2 production, and energy expenditure during the Dark phase in the youngest rat group. In addition, melatonin deficit elevated arterial blood pressure (systolic, diastolic, and mean arterial pressure) and increased serum glucose and triglyceride level in 3-month-old rats while decreased the liver enzyme activity in 14-month-old rats. In conclusion, the present study brought new insights confirming the complex impact of melatonin deficit on important physiological, metabolic and biochemical markers related to aging and demonstrated for the first time that the lack of melatonin hormone is harmful in young adult rats.

Melatonin and miscarriage

Abstract: Spontaneous abortions (abortion up to 22 weeks of gestation since the last menstrual cycle or with a fetal weight of less than 500.0 g) occur in 15-20% of the total number of registered pregnancies. The incidence of miscarriages increases up to 15% in women under 25 and to 35% and more in women over 38. Causes of miscarriages can be divided into two categories: those which associated with chromosomal abnormalities and those which associated with disruption of the intrauterine environment.Some studies have shown the infl uence of systematic and placental oxidative stress in the pathophysiology of abortion and repeated «stop» of pregnancy. Lack of antioxidant protection leads to recurrent abortions. Membranes’ damages with the production of lipid peroxides, which are induced by reactive oxygen species (ROS), as well as due to certain disorders or disorganization, immediately cause abortion. There are versions that pineal insuffi ciency may be associated with spontaneous abortions, even in cases where there are no chromosomal abnormalities and structural disorders of the uterus. This hypothesis is based on the fact that melatonin is a strong antioxidant which binds free radicals and its concentration normally increases signifi cantly during pregnancy and in pinealectomy rats the frequency of miscarriages increases. Melatonin has an immunomodulatory eff ect. It stimulates the secretion of progesterone, which reduces the degree of uterine contraction and prevents immunological rejection of the trophoblast, inhibits the synthesis of prostaglandins, which can potentially induce uterine contractions. Pinealectomy leads to a signifi cant reduction of circulating in blood melatonin level and to abortion in rats.

0813 Post-Pinealectomy Insomnia and Melatonin Therapy

Abstract: Melatonin is a hormone produced in the pineal gland that has an important role in sleep; immune, neurologic, psychiatric, metabolic, and endocrinologic function; cardiac-autonomic regulation and even cancer risk. We present a case of insomnia, somnambulism, dream enactment, and periodic limb movements of sleep (PLMS) after a pinealectomy. Report of Cases: A 40-year-old woman with a history of a complete pinealectomy due to a pineal cyst presented to the sleep medicine clinic. Shortly after the pinealectomy, she developed sleep onset and maintenance insomnia. Two years later she developed somnambulism, and four years later she developed dream enactment and PLMS. She reported no prior treatments for her sleep issues, including no history of melatonin use. On average, her total sleep time (TST) was 2-8 hours/night with awakenings every 2 hours. Sleep latency was 10-45 minutes. Polysomnograghy demonstrated an apnea-hypopnea index of 0.6/hr, PLM index of 68.1/hr, normal REM atonia, and no complex behaviors. The patient started 1mg immediate release (IR) melatonin, which did not help her insomnia, but parasomnias resolved. She had improvement in her PLMS with iron supplementation and melatonin. The melatonin dose was increased to 3mg IR which helped increase her TST to 4-8 hours. She was switched to 3mg extended release (ER) melatonin, and then increased to 4mg ER. She obtained the most benefit for her insomnia with 1mg IR plus 4mg ER with sleep latency reduced to 5-10 minutes and TST improved up to 7.5 hours with rare awakenings. Pinealectomy in humans is rarely reported. Most data about the consequences of pinealectomy and pathophysiology of melatonin come from animal research. Melatonin level after pinealectomy is often undetectable or severely diminished. Current limited literature on patients with pinealectomy consists of case reports about patients who experienced insomnia, non-24-hour sleep-wake rhythm disorder [SSM1] and mood disorders. Melatonin doses ranging from 0.5mg to 14mg IR and up to 5mg ER have been trialed with most patients having symptomatic improvement with doses above 3mg. We found that a combination of 1mg immediate and 4mg extended release melatonin was the most beneficial for our patient.

Emotional Disturbance in Two Models of Melatonin Deficiency: A Comparative Study

Abstract: In the present study, the aim was to compare the role of melatonin deficiency on emotional status in two different models, chronic constant light (CCL) and pinealectomy in male Wistar rats. While the rats with pinealectomy (Pin) showed impulsive behaviour (increased motor activity and lack of anxiety), CCL-rats demonstrated higher anxiety in the elevated plus-maze test (EPM). Slight differences in depressive-like behaviour, measured by the saccharine preference test (SPT) and the forced swimming test (FST), were also detected. The CCL-rats exhibited anhedonia only during the active (dark) phase of the light-dark cycle whereas rats with removed pineal gland showed depressive behaviour without diurnal variations. Immobility in the FST was increased in the two models of melatonin deficiency. Exposure to CCL and removal of the pineal gland abolished the circadian fluctuations in plasma melatonin levels. Both models of melatonin deficit exhibited higher plasma corticosterone levels during the light period and blunted diurnal variations of the hormone. Our findings suggest that models of melatonin deficiency recapitulate several neurobiological alterations associated with melancholic depression. Future studies are needed to elucidate the precise mechanism related to the model-specific difference in emotional status.

Pinealectomy and melatonin administration in rats: their effects on pulmonary edema induced by α-naphthylthiourea.

Abstract: We aimed to observe the possible effects of melatonin (MLT) deprivation (pinealectomy) and exogenous MLT administration on pulmonary edema induced by alpha-naphthylthiourea (ANTU), a toxic chemical agent, in rats. Seventy animals were assigned to seven groups: control, sham pinealectomy (PINX), PINX, ANTU (10 mg/kg intraperitoneal on day 30), ANTU + MLT (10 mg/kg/day i.p. for 30 days), ANTU + PINX, and ANTU + PINX + MLT.In this study, pleural effusion (PE) formation, lung weight/body weight (LW/BW) and PE/BW ratios (fluid accumulation and weight values in the lungs) increase detected. Pre-ANTU MLT administration led to significant decreases in PE, LW/BW, and PE/BW levels. The inhibited glutathione (GSH) and superoxide dismutase (SOD) levels and high malondialdehyde (MDA) levels that ANTU increase lipid peroxidation in the study. MLT administration eliminated oxidative stress by reducing MDA and ameliorating GSH and SOD levels.Pre-ANTU MLT administration led to a significant decrease in interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) levels in the lung when compared to the ANTU group without MLT administration. Post-pinealectomy ANTU administration significantly increased IL-1β and TNF-α levels when compared to ANTU and MLT administration without pinealectomy. Diffused inflammatory cell infiltration, interstitial pulmonary edema, and histopathological congestion were observed after the administration of ANTU. Severity of the damage was elevated in the ANTU + PINX group. MLT treatment regressed pulmonary effusion and edema and improves lung structure. In brief, the findings suggested that MLT inhibited proinflammatory mediators and could serve as a therapeutic agent to prevent inflammatory disorders.