Opioids such as morphine and fentanyl are widely used for pain management and in cardiovascular conditions; however, their misuse has become a significant public health concern. Non-cardiogenic pulmonary edema is a hallmark of opioid intoxication, often associated with impaired alveolar fluid clearance (AFC), a sodium transport–driven process that removes excess fluid from the alveoli. This study aimed to elucidate the potential mechanisms of morphine-induced pulmonary edema by investigating the effects of μ-, δ-, and κ-opioid receptor (MOR, DOR, and KOR) modulation on AFC in rat lungs and determining whether receptor-specific blockade alters sodium transport across the alveolar epithelium. Adult male Wistar rats were anesthetized, and a 5

Alzheimer's disease (AD), the most frequent neurodegenerative disease within dementias, affects the CNS, leading to gradual memory issues and cognitive dysfunction. Oxidative stress in AD contributes to ongoing neuronal loss and hastens disease progression. Notably, the potent antioxidant compounds morin and hesperidin have demonstrated significant effectiveness in addressing oxidative stress. This study explores the impact of morin and hesperidin on behavior and oxidative stress in the streptozotocin (STZ)-induced AD rat model. The experiment involved five groups: control, STZ, STZ+morin, STZ+hesperidin, and STZ+morin+hesperidin. The rat model of AD was created by injecting STZ with the stereotaxic surgery. Morin and hesperidin were applied to the groups for 7-days. After the applications, the Morris water maze (MWM) and novel object recognition (NOR) tests were used and the rats were sacrificed. Malondialdehyde (MDA), glutathione (GSH), nitric oxide (NOx), and protein carbonyl (PC) levels were measured. In the STZ group, the levels of NOx and PC exhibited a noteworthy increase compared to the control. Conversely, the application of morin and/or hesperidin treatments reduced NOx and PC levels compared to the STZ group. The co-administration of morin and hesperidin improved the antioxidant status and decreased lipid peroxidation in STZ-induced rats. In the STZ group, serum advanced oxidation protein products (AOPP) levels were statistically elevated compared to the control. However, in the treatment groups, morin and/or hesperidin successfully decreased AOPP levels to those observed in the control. The combined use of these flavonoids may have a neuroprotective effect regarding memory problems and decreasing oxidative/nitrosative stress.

Introduction: We evaluated the effects of repeated ketamine, propofol, and ketamine + propofol administration on cognitive functions and brain tissue of elderly rat models with streptozotocin-induced Alzheimer’s disease. Materials and Methods: Thirty elderly male Wistar Albino rats were divided into five groups: control (Group C), Alzheimer’s (Group A), Alzheimer’s + ketamine (Group AK), Alzheimer’s + propofol (Group AP), and Alzheimer’s + propofol + ketamine (Group APK). Alzheimer’s disease was induced in Groups A, AK, AP, and APK via intracerebroventricular streptozotocin. Four weeks after surgery, ketamine, propofol, and ketamine + propofol were administered intraperitoneally for 3 days to Groups AK, AP, and APK, respectively. The radial arm maze test (RAMT) was performed in the initial, 1st, 2nd, 3rd, and 4th weeks after surgery and daily following anaesthesia. Blood and brain tissue samples were obtained. Results: The RAMT results of Groups A, AK, AP, and APK decreased compared to Group C 2 weeks after Alzheimer’s disease onset. Compared to Group A, the RAMT results increased in Groups AK and APK after the first anaesthesia, and in Group AP after the second anaesthesia. Brain tissue paraoxonase-1 (PON-1) and catalase (CAT) activities were low, and the thiobarbituric acid reactive substance (TBARS) level was high in Group A compared to Group C. TBARS levels of Groups AP and APK were lower than Group A, while CAT activity was higher. PON-1 activity was higher in Groups AK, AP, and APK than in Group A. Histopathological changes decreased in Groups AP and AK. A decrease in p53 was found in Group C compared to Group A. Ketamine and propofol were found to be effective at Bcl-2 immunoexpression, but a decrease in Caspase-3 was observed in Group APK. GFAP immunoexpression increased in Group A compared to Group C and in Group AP compared to Group AK. Conclusions: Repetitive anaesthesia application was found to positively affect cognitive functions. This was supported by histopathological and biochemical markers.

Alzheimer’s disease (AD) is the most common form of dementia that occurs in the brain. This is a chronic neurodegenerative disease which is valid in 60–70% of all dementia patients. Boron, regarded as a potential antioxidant, has the effect of reducing oxidative stress. Taurine, as one of the thiol-containing amino acids, exists at different concentrations in both the neurons and glial cells of the central nervous system. It plays an important role in the protective and adjuvant therapies as an antioxidant due to its characteristics of maintaining the oxidant-antioxidant balance of the body as well as cell integrity and increasing body resistance. Based on this information, our objective was to reveal the effect of boron alone, taurine alone plus co-administration of taurine and boron application on brain tissue protein carbonyls (PC) and serum advanced oxidation protein products (AOPP) levels in the experimental Alzheimer’s model. For this purpose, 5 groups were formed in our study which consisted of 30 Wistar albino male rats. The rats were given a single dose of STZ stereotaxically. At the end of this period, the rats were decapitated, plus their brain tissues and blood were removed. Our findings suggested that taurine alone and co-administration of boron and taurine had a decreasing effect on AOPP and PC levels of the experimental Alzheimer model of the rats.

Background/aim Physical exercise is a state of physiological stress that requires adaptation of the organism to physical activity. Glycogen is an important and essential energy source for muscle contraction. Skeletal muscle and liver are two important glycogen stores, and the energy required to maintain exercise in rodents are provided by destruction of this glycogen depot. In this study, the effects of endogenous opioid peptide antagonism at the central nervous system level on tissue glycogen content after exhaustive exercise were investigated. Materials and methods Rats had intracerebroventricularly (icv) received nonspecific opioid peptide receptor antagonist, naloxone (50 μg/10 μL in saline) and δ-opioid receptor-selective antagonist naltrindole (50 μg/10 μL in saline) and then exercised till exhaustion. After exhaustion, skeletal muscle, heart, and liver were excised immediately. Results Both opioid peptide antagonists decreased glycogen levels in skeletal muscle. Although, in soleus muscle, this decrease was not statistically significant (p > 0.05), in gastrocnemius muscle, it was significant in the icv naloxone administered group compared with control (p < 0.05). Heart glycogen levels increased significantly in both naloxone and naltrindole groups compared to control and sham-operated groups (p < 0.05). Heart glycogen levels were higher in the naloxone group than naltrindole (p < 0.05). Liver glycogen levels were elevated significantly with icv naloxone administration compared with the control group (p < 0.05). Glycogen levels in the naloxone group was also significantly higher than the naltrindole group (p < 0.05). Conclusion Our findings indicate that icv administered opioid peptide antagonists may play a role in glycogen metabolism in peripheral tissues such as skeletal muscle, heart, and liver.

Objectives: The aim of this study was to investigate the association between Alzheimer's disease and erythrocyte deformability and to assess whether recurrent sevoflurane anesthesia influenced this association. Methods: A total of 24 Wistar albino rats were divided into four groups: Control, sevoflurane, Alzheimer, and Alzheimer + sevoflurane. The experimental Alzheimer model was prepared by intracerebroventricular injection of streptozotocin at a dose of 3 mg/kg (10 μl) to the Alzheimer and Alzheimer + sevoflurane groups. Sevoflurane (2.3%) was administered to the sevoflurane and Alzheimer + sevoflurane groups 4 weeks after the surgery for 3 days and lasting for 2 hours per day. Blood samples were then collected for deformability measurements. Results: The deformability index was significantly increased in Alzheimer-induced rats, but the results for the Alzheimer and Alzheimer + sevoflurane groups were similar. The erythrocyte deformability index was significantly increased in the Alzheimer and Alzheimer + sevoflurane groups (p=0.004 p=0.001 respectively). However, there was no difference in deformability in the sevoflurane group (p= 0.496) Conclusion: Erythrocyte deformability was increased in the Alzheimer-induced rats; however recurrent sevoflurane anesthesia did not affect erythrocyte deformability.

The aim of this review is to summarize current studies on the relationship between melatonin and aging. Nowadays, age-related diseases come into prominence, and identifying age-related changes and developing proper therapeutic approaches are counted as some of the major issues regarding community health. Melatonin is the main hormone of the pineal gland. Melatonin is known to influence many biological processes in the body, including circadian rhythms, the immune system, and neuroendocrine and cardiovascular functions.Melatoninrhythms also reflect the biological process of aging. Aging is an extremely complex and multifactorial process. Melatonin levels decline considerably with aging and its decline is associated with several age-related diseases. Aging is closely associated with oxidative damage and mitochondrial dysfunction. Free radical reactions initiated by the mitochondria constitute the inherent aging process. Melatonin plays a pivotal role in preventing age-related oxidative stress. Coronavirus disease 2019 (COVID-19) fatality rates increase with chronic diseases and age, where melatonin levels decrease. For this reason, melatonin supplementation in elderly could be beneficial in COVID-19 treatment. Therefore, studies on the usage of melatonin in COVID-19 treatment are needed.

Objective: Hypoxic preconditioning allows cells to gain resistance to hypoxic damage. There are a limited number of studies suggesting that hypoxic preconditioning increases antioxidant capacity in the lung. In this study, we aimed to evaluate effects of hypoxic preconditioning on oxidant/ antioxidant systems in rat lung. Material and Methods: Rats were divided into 4 groups: control, preconditioning (PC) (10% O2), severe hypoxia (SH) (7% O2) and PC + SH. The parameters related to oxidative stress and antioxidant defense mechanisms, which are malondialdehyde (MDA) levels, total oxidant system (TOS), total antioxidant capacity (TAC), oxidative stress index (OSI), superoxide dismutase (SOD) and glutathione (GSH) activity, were measured. Results were evaluated using the One-Way ANOVA and t-test; p<0.05 was considered significant. Results: Compared with the control group, MDA levels decreased in all hypoxic groups; decrements in PC and SH groups were statistically significant. Compared with the control group, levels of TOS showed a significant increase in the PC+SH group. OSI of PC+SH group was significantly higher than other groups. There was no significant difference in TAC levels between the groups. Compared to other groups, SOD activity showed a significant decrease in the PC+SH group. GSH levels showed a significant decrease in PC+SH group compared to both control and PC group. Conclusion: Our findings suggest that hypoxic preconditioning does not have an effect on antioxidant defense systems in lungs, but severe hypoxia does affect oxidant/antioxidant systems.

Background/aim The purpose of the present study was to explore the neuroprotective role of delta opioid receptors (DOR) in the rat cortex in hypoxic preconditioning. Materials and methods Rats were randomly divided into 8 groups: control (C), sham (S), hypoxic preconditioning (PC), severe hypoxia (SH), PC + SH, PC + SH + Saline (PS), PC + SH + DPDPE (DPDPE, selective DOR agonist), PC + SH + NT (NT, Naltrindole, selective DOR antagonist). Drugs were administered intracerebroventrically. Twenty four h after the end of 3 consecutive days of PC (10% O2, 2 h/day), the rats were subjected to severe hypoxia (7% O2 for 3 h). Bcl-2 and cyt-c were measured by western blot, and caspase-3 was observed immunohistochemically. Results Bcl-2 expressions in the PC group were higher than in control, SH, and PC + SH groups. Even though there were no significant differences between the groups in terms of cyt-c levels, caspase-3 immunoreactivity of cortical neurons and glial cells in the severe hypoxia and NT groups were higher than in the control, sham, and hypoxic preconditioning groups. DPDPE administration diminished caspase-3 immunoreactivity compared with all of the severe hypoxia groups. Conclusions These results suggest that cortical cells are resistant to apoptosis via increased expression of Bcl-2 and decreased immunoreactivity of caspase-3 in the cortex, and that DOR is involved in neuroprotection induced by hypoxic preconditioning via the caspase-3 pathway in cortical neurons.

We investigated the protective effect of vitamin D against liver damage caused by carbon tetrachloride (CCl4). Twenty-four male rats were divided into four equal groups: G1, untreated controls; G2, administered CCl4; G3, administered both CCl4 and vitamin D for 10 weeks; G4, administered CCl4 for 10 weeks and vitamin D for 12 weeks. At the end of experiment, intracardiac blood samples were taken and liver samples were removed. Hepatic damage due to CCl4 was assessed using biochemistry and histopathology. Glutathione (GSH) levels decreased, while malondialdehyde (MDA) levels increased in liver tissues of G2. Alanine transaminase (ALT), alkaline phosphatase (ALP), and gamma-glutamyl-transaminase (GGT) levels increased, while albumin (ALB) levels decreased. Hepatocyte degeneration, lobular disorder, sinusoid dilation, focal necrotic areas, hyperemia, and glycogen loss were observed. Hepatic fibrosis was observed around portal areas and central veins. Bridging fibrous septa were formed between portal veins. By immunohistochemistry, both matrix metalloproteinase-9 (MMP-9) and desmin reactivity were increased. All aspects of liver damage were at least partially prevented in rats treated with vitamin D. Vitamin D appears to act as an antioxidant and anti-fibrotic to protect the rat liver against damage.

Ischemia-reperfusion (I/R) injury induces the generation of reactive oxygen species (ROS) which affect many organs. This study was designed to investigate the roles of melatonin and 1,25-dihydroxyvitamin D-3 (VD3) on renal I/R injury. Thirty male Wistar albino rats were divided into five groups: group 1, control; group 2, right nephrectomy (RN) + I/R in the contralateral kidney; group 3, melatonin + RN + I/R; group 4, VD3 + RN + I/R; and group 5, melatonin + VD3 + RN + I/R. Melatonin (10 mg/kg), VD3 (0.5 mu g/kg), and melatonin plus VD3 were injected intraperitoneally for 7 days before renal I/R. After 7 days, right nephrectomy was initially performed and left renal artery was clamped for 45 min. After 45-min reperfusion, the serum and kidney tissue samples were obtained for assays. Melatonin and VD3 had an ameliorative effect on biochemical parameters such as serum creatinine (SCr) and blood urea nitrogen (BUN). Renal tissue malondialdehyde (MDA), glutathione (GSH), nitric oxide (NO) levels, and superoxide dismutase (SOD) activity were determined. Renal I/R decreased the kidney tissue GSH levels and SOD activity and increased the NO levels as compared with control group. However, melatonin and VD3 and melatonin plus VD3 treatment significantly increased the tissue GSH levels and SOD activity and decreased the NO levels compared with those of I/R group. Meanwhile, MDA levels were not different between the control and I/R groups. But, MDA levels decreased in all treated groups compared to I/R and control groups. These data support that melatonin and VD3 have beneficial effects on renal injury.

Aging is believed to be a first-order risk factor for most neurodegenerative disorders. The neuronal cell loss that occurs with aging has been partly attributed to increased production of nitric oxide and high caspase activity. Melatonin (MLT) might have a role in the regulation of nitric oxide in the brain. We investigated the effects of MLT on the nitrite/nitrate levels and caspase-3 enzyme activity in the frontal cortex, temporal cortex, and hippocampus of young and aged rats. There was no significant difference between the nitrite levels in the frontal cortex and hippocampus of young and aged animals. In the temporal cortex of aged rats, the nitrite level, however, was significantly higher (P < 0.001). In the aged group, MLT significantly decreased these levels in the brain regions. Caspase-3 enzyme activity in the temporal and frontal cortices was significantly higher in aged rats when compared to the control group (P < 0.05). Melatonin did not cause significant changes in caspase-3 activity in any brain region of both young and aged rats. Thus, brain regions demonstrate different caspase-3 enzyme activities and nitrite levels in the aging process. Exogenous MLT administration might delay brain aging (by moderation of death of neurons and glia) via decreasing the nitrite/nitrate level.

Background: Oxidative stress is involved in several pathologic conditions such as metabolic or cardiovascular disease, and in aging. Oxidative damage of biomolecules increases with age. Melatonin is the main neurohormone of the pineal gland and specific antioxidants may act against age-related oxidative damage.Objective: This study investigated the effects of administration of melatonin on aging-related parameters such as total oxidant status (TOS), hydrogen peroxide (H2O2) and lipid hydroperoxide (LOOH) levels and total antioxidant capacity (TAC) in the heart and liver in a rat model of aging.Methods: Young (3-month-old) and aged (24-month-old) male Wistar rats were divided into control and melatonin-treated groups. Melatonin was given for 21 days (10 mg/kg/day). At the end of the treatment period, TOS, TAC, H2O2, and LOOH levels were measured.Results: H2O2 in the liver, but not in the heart, was found to be increased in aged rats. Melatonin treatment diminished H2O2 in the heart of both group of rats compared with those of untreated control rats. Melatonin treatment also led to a decrease in H2O2 in the liver of aged rats. LOOH were found to be increased in both tissues of aged rats whereas melatonin treatment decreased LOOH levels in heart and liver tissues of aged rats. In the young rats melatonin also inhibited LOOH in liver. TAC in heart and liver was not found to be statistically different between young and aged rats. In young rats, melatonin treatment resulted in an increase in TAC that was associated with increased H2O2. In the liver and heart of the rats, TOS was increased with age and was ameliorated by melatonin treatment.Conclusion: Our results demonstrate that there is no dramatic overall decline in the antioxidant system with age. However, total oxidant status increased with age. Melatonin has a restorative effect on oxidative status. Copyright (C) 2012, Taiwan Society of Geriatric Emergency & Critical Care Medicine. Published by Elsevier Taiwan LLC. All rights reserved.

Physical exercise increases the level of endogenous opiates that possibly play a major role for integration of hormonal and metabolic responses to exercise. Increased endogenous opioids in response to physical activity may enhance the performance through decreasing pain perception. However, what possible effect the opioid peptides have on physical exercise at the level of central nervous system remains to be elucidated. In this study, naloxone (N = 6), and naltrindole (N = 8) were administered intracerebroventrically to rats. A physiologic saline group (N = 10) and a control group (N = 8) were also included in the study. All groups were then subjected to exhaustive exercise on a treadmill. Besides recording the exhaustion time, blood glucose and lactate levels were measured before and after exercise. Treatments with naloxone and naltrindole had no effect on the exhaustion time. In comparison with pre-exercise period, lactate levels increased, while glucose levels decreased significantly in the blood of all animals during post-exercise period. However, decreased level of glucose in the post-exercise period was statistically significant only in those treated with naltrindole, compared with the other groups. Our findings indicate that the central endogenous opioid peptides may have a role in the regulation of glucose metabolism during exhaustive exercise. This effect can be mediated via delta opioid receptors, although they exert no effect on the performance, namely, on the exhaustion time.

During magnetic resonance imaging, there is an interaction between the time-varying magnetic fields and the active implantable medical devices (AIMD). In this study, in order to express the nature of this interaction, simplified analytical expressions for the electric fields induced by time-varying magnetic fields are derived inside a homogeneous cylindrical volume. With these analytical expressions, the gradient induced potential on the electrodes of the AIMD can be approximately calculated if the position of the lead inside the body is known. By utilizing the fact that gradient coils produce linear magnetic field in a volume of interest, the simplified closed form electric field expressions are defined. Using these simplified expressions, the induced potential on an implant electrode has been computed approximately for various lead positions on a cylindrical phantom and verified by comparing with the measured potentials for these sample conditions. In addition, the validity of the method was tested with isolated frog leg stimulation experiments. As a result, these simplified expressions may help in assessing the gradient-induced stimulation risk to the patients with implants.