Impact of Lithium on the Immune System: An Investigation of T-Cell Subpopulations and Cytokine Responses in Rats.

The aim of this study was to investigate the dose-dependent adverse effects of long-term dietary lithium administration on specific aspects of the defense system in rats. Additionally, the study aimed to explore the inflammatory activities of lithium beyond its recognized anti-inflammatory properties. Forty Wistar Albino rats were involved, which were randomly allocated into the control and four treatment groups. The control group received standard rat feed, and the experimental groups' diet was added 1 g/kg, 1.4 g/kg, 1.8 g/kg, and 2.2 g/kg lithium bicarbonate, respectively. CD4+, CD8+, and CD161 + cells were assessed by flow cytometry. TNF-α, IFN-γ, IL-1ß, and IL-2 and IL-4, IL-6, and IL-10 levels were measured. The proportion of CD4 + cells and the CD4+/CD8 + ratio (P = 0.005 and P = 0.038, respectively) were reduced with the highest dose of lithium compared to the control group. The data regarding pro-inflammatory cytokines showed a dose-dependent increase in serum TNF-α and IFN-γ levels (P = 0.023 and P = 0.001, respectively). On the other hand, serum IL-1ß and IL-2 levels were decreased in a dose-dependent manner (P = 0. 001 and P = 0. 001, respectively). As for anti-inflammatory cytokines, a dose-dependent decrease was determined in serum IL-4 level (P = 0.002), while no significant changes were noted in IL-6 and IL-10 levels (P = 0.507 and P = 0.732, respectively). In conclusion, lithium adversely impacted the cellular defense system. Furthermore, apart from its anti-inflammatory properties, lithium exhibited cytokine-mediated inflammatory activities. Therefore, lithium's potential adverse effects on the immune system should be considered in immunodeficient patients and those with an inflammatory status treated with high doses of lithium.

Erythroid microRNA and oxidant status alterations in l-thyroxine-induced hyperthyroid rats: effects of selenium supplementation.

BACKGROUND: Hypermetabolic state in hyperthyroidism causes oxidative stress. Erythrocytes are the cells that are involved in oxidant equilibrium in an organism and contain microRNA (miRNA). Selenium, which is an essential element for an organism, has antioxidant properties. The present study was aimed at investigating the effects of selenium supplementation in hyperthyroidism, on pro- and antioxidant enzymes, and miRNA (miR-144 and miR-451) expressions in the erythrocytes. METHODS: Forty-eight Sprague-Dawley male rats were divided into 6 groups; control group, group fed with 0.5 mg/kg sodium selenite; group fed with 1 mg/kg sodium selenite; hyperthyroid group; hyperthyroid group fed with 0.5 mg/kg sodium selenite; and hyperthyroid group fed with 1 mg/kg sodium selenite. Malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), miR-144, and miR-451 expression levels were studied in erythrocyte hemolysates. RESULTS: MDA levels were increased in the hyperthyroid group compared to the control group, and the group fed with 0.5 mg/kg sodium selenite (P<0.001 and P<0.01, respectively). GSH levels were increased in the hyperthyroid group and the hyperthyroid group fed with 0.5 mg/kg sodium selenite compared to the control group (P<0.001, and P<0.05, respectively). GSH levels of the hyperthyroid group fed with 1 mg/kg sodium selenite were decreased when compared with the hyperthyroid group (P<0.05). SOD levels of the hyperthyroid group were increased when compared with the control group (P<0.05, and P<0.001, respectively). Similarly, SOD levels of the hyperthyroid group fed with 1 mg/kg sodium selenite were lower than the hyperthyroid group (P<0.01). miR-144 values were increased in the hyperthyroid group and the hyperthyroid group fed with 0.5 mg/kg sodium selenite compared to the control group (P<0.001, and P<0.05 respectively). miR-451 expression was increased significantly in the hyperthyroid group compared to the control group (P<0.05). CONCLUSIONS: Our findings showed that MDA, SOD and GSH levels increased, and miR-144 and miR-451 expressions changed in hyperthyroidism. Supplementation of 1 mg/kg sodium selenite was more effective than 0.5 mg/kg sodium selenite for normalizing the MDA, GSH, SOD, and miRNA levels in the hyperthyroid group.

Monitoring of platelet function parameters and microRNA expression levels in patients with prostate cancer treated with volumetric modulated arc radiotherapy.

Radiotherapy (RT) may result in platelet activation and thrombosis development. To the best of our knowledge, the potential effect of volumetric-modulated arc therapy (VMAT), a novel radiotherapy technique, on platelet function and microRNA (miRNA/miR) expression has not been previously investigated. The present study aimed to determine the effect of VMAT on the alterations in platelet function parameters and miRNA expression levels. A total of 25 patients with prostate cancer and 25 healthy subjects were included in the present study. Blood samples were collected from the patient group on the day prior to RT (pre-RT), the day RT was completed (post-RT day 0), and 40 days following the end of therapy (post-RT day 40). Platelet count, mean platelet volume (MPV) value, platelet aggregation, plasma P-selectin, thrombospondin-1, platelet factor 4, plasma miR-223 and miR-126 expression levels were measured. A significant decrease in platelet count in the post-RT day 0 group was measured in comparison with the pre-RT and the post-RT day 40 groups. Pre-RT MPV values were higher than those of the post-RT day 0 and the post-RT day 40 groups. No significant differences were observed in the levels of platelet activation markers or miR-223 and miR-126 expression levels between the RT groups. Although RT may result in a reduction in platelet and MPV counts, the results of the present study indicate that platelet activation markers are not affected by VMAT. Therefore, it is possible that no platelet activation occurs during VMAT, owing to the conformal dose distributions, improved target volume coverage and the sparing of normal tissues from undesired radiation.

The Effects of Lithium Administration on Oxidant/Antioxidant Status in Rats: Biochemical and Histomorphological Evaluations.

Present study was planned to determine possible dose-dependent effects of lithium (Li) on oxidant-antioxidant status and histomorphological changes in liver and kidney tissues. For this purpose, twenty-four Wistar male rats were equally divided into three groups: the rats in group I served as controls, drinking tap water without lithium. Groups II and III received 0.1 and 0.2 % lithium carbonate (Li2CO3) through their drinking water, respectively, for 30 days. At the end of the experimental period, lithium concentrations, levels of malondialdehyde (MDA) and glutathione (GSH) and superoxide dismutase (SOD) activities were measured in considered tissues. Histomorphological study was also performed on liver and kidney tissues. Compared to controls, MDA was significantly higher but GSH level lower in groups II and III. SOD activity was higher in group III, but no difference was determined in group II in liver tissue. In kidney tissue, there was no difference determined in MDA and GSH levels between control and experimental groups but SOD activity in groups II and III was significantly higher. In histologic sections of both experimental liver and kidney tissues, specific degenerations were observed. The results of the present study show that treatment with lithium carbonate may result in liver and kidney tissue abnormalities and oxidative damage.

Lithium-induced hypothyroidism: oxidative stress and osmotic fragility status in rats.

The present study was conducted to explore the possible effects of different doses of lithium carbonate on thyroid functions, erythrocyte oxidant-antioxidant status, and osmotic fragility. Twenty-four Wistar-type male rats were equally divided into three groups: groups I and II received 0.1 and0.2 % lithium carbonate in their drinking water, respectively, for 30 days. The rats in group III served as controls, drinking tap water without added lithium. At the end of the experimental period, the erythrocyte osmotic fragility and the levels of triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) were measured in blood samples. Compared to controls, there was a statistically significant increase of TSH but decreases of the T3 and T4 levels in group II. Both experimental groups showed a statistically significant increase of the maximum osmotic fragility limit. The minimum osmotic fragility values of the animals in group II were statistically higher than those of controls. The standard hemolytic increment curve of both experimental groups was shifted to the right when compared to the curve obtained from the controls. Also, relative to controls, the activities of MDA and SOD were significantly higher and the GSH level lower in group II, but not so in group I. The results of the present study show that treatment with lithium carbonate may result in thyroid function abnormalities, increased oxidative damage, and possible compromise of the erythrocyte membrane integrity resulting from increased osmotic fragility.

The effects of chronic long-term intermittent hypobaric hypoxia on blood rheology parameters.

The effect of chronic long-term intermittent hypobaric hypoxia (CLTIHH) on blood rheology is not completely investigated. We designed this study to determine the effect of CLTIHH on blood rheology parameters. Present study was performed in 16 male Spraque-Dawley rats that divided into CLTIHH and Control groups. To obtain CLTIHH, rats were placed in a hypobaric chamber (430 mmHg; 5 hours/day, 5 days/week, 5 weeks). The control rats stayed in the same environment as the CLTIHH rats but they breathed room air. In the blood samples aspirated from the heart, hematocrit, whole blood viscosity, plasma viscosity, plasma fibrinogen concentration, erythrocyte rigidity index and oxygen delivery index were determined. The whole blood viscosity, plasma viscosity, hematocrit and fibrinogen concentration values in the CLTIHH group were found to be higher than those of the control group. However, no significant difference was found in erythrocyte rigidity index and oxygen delivery index between the groups. Our results suggested that CLTIHH elevated whole blood viscosity by increasing plasma viscosity, fibrinogen concentration and hematocrit value without effecting the erythrocyte deformability. Hence, CLTIHH that may occur in intermittent high altitude exposure and some severe obstructive sleep apnea (OSA) patients may be responsible for hemorheologic changes in those subjects.

The effects of ß-glucan on iron levels and lipid peroxidation in intra-abdominal sepsis in rats.

Sepsis is defined as a systemic response of organisms to microorganisms and toxins. Sepsis is associated with the enhanced generation of reactive oxygen metabolites, leading to multiple organ dysfunctions. ß-glucan is accepted to be one of the most powerful immune response modifiers. The aim of this study was to investigate the putative protective effect of ß-glucan on changes of iron and malondialdehyde (MDA) levels in various tissue and blood after experimental sepsis in rats. Sepsis was induced by cecal ligation and perforation (CLP) in 32 male Wistar albino rat. To evaluate this, rats were divided into four groups as sham operated, ß-glucan treated sham operated, CLP and ß-glucan treated CLP. Sixteen hours after operation, rats were decapitated and MDA and iron levels were measured in the liver, kidney, heart, diaphragm tissues and blood. Also, whole tissue histopathology was evaluated by a light microscope. The results demonstrate that sepsis significantly decreased iron levels of all tissues and blood. The decrease in tissue iron levels and the increase MDA levels demonstrate the role of trace elements and free radicals in sepsis-induced tissue damage. Our results indicate that the given dose of ß-glucan was probably insufficient to prevent sepsis-induced organ injury.

Erythrocyte osmotic fragility and lipid peroxidation in experimental hyperthyroidism.

This study investigated the relation between erythrocyte osmotic fragility and oxidative stress and antioxidant state in primary hyperthyroidism induced experimental rats. Twenty-four Spraque-Dawley-type female rats weighing between 160 and 200 g were divided into two, as control (n = 10) and experimental (n = 12), groups. The experimental group animals have received tap water and L-Tiroksin (0.4 mg/100 g fodder) added standard fodder for 30 days to induce hyperthyroidism. Control group animals were fed tap water and standard fodder for the same period. Blood samples were drawn from the abdominal aorta of the rats under ether anesthesia. T3, T4, and TSH levels, osmotic fragility, malondialdehyde (MDA), superoxide dismutase, and glutathione levels were measured in the blood. There was a statistically significant deviation found in maximum and minimum osmotic hemolysis limit values of experimental group when compared to controls. The standard hemolytic increment curve of the hyperthyroid group shifted to the right when compared to control group's curve. There was a statistically significant increase found in MDA and superoxide dismutase, but statistically a significant decrease was detected in glutathione levels in hyperthyroid group when compared to controls. As a result of our study, it may be concluded that hyperthyroidism may led to an increase in osmotic fragility of erythrocytes and this situation may possibly originate from the increased lipid peroxidation in hyperthyroidism.

The effect of ß-glucan on trace element levels in intra-abdominal sepsis in rats.

Sepsis is associated with the development of progressive damage in multiple organ systems. The beneficial effect of glucans has been attributed to modulation of immune function and enhances defense against bacterial, viral, fungal, and parasitic infections. The aim of this study was to investigate the putative protective effect of ß-glucan on changes of trace element levels in various tissues after experimental sepsis in rats. Sepsis was induced by cecal ligation and perforation (CLP) in 28 male Wistar albino rats. To evaluate this, rats were divided into four groups as sham operated, ß-glucan treated sham operated, CLP, and ß-glucan treated CLP. Sixteen hours after operation, rats were decapitated and zinc (Zn) and copper (Cu) levels were determined in the liver, kidney, heart, diaphragm, and lung tissues. The results demonstrate that sepsis significantly decreased zinc and copper levels of all tissues. The decrease in tissue zinc and copper levels demonstrates the role of trace elements in sepsis-induced tissue damage. Our results indicated that ß-glucan administration did not return the zinc and copper levels to the control group level, and it seems likely that the given dose of ß-glucan was insufficient to prevent sepsis-induced organ injury.

Significance of the counteracting oxidative and antioxidative systems in the pathogenesis of laryngeal carcinoma.

OBJECTIVE: To evaluate the parameters of oxidative and antioxidative systems in laryngeal carcinoma for their effects on pathogenesis. METHODS: Blood and plasma samples from 30 patients with laryngeal carcinoma were compared with 15 smokers who were otherwise healthy. The tumour tissue samples of the 30 patients were compared with the adjacent non-tumour-bearing mucosal tissue in which carcinoma was ruled out histologically. Although malondialdehyde was used as the main indicator of oxidative stress, superoxide dismutase, glutathione, and catalase activities were accepted as indicators of the antioxidative defense mechanism. RESULTS: Malondialdehyde was significantly higher in the plasma and blood of patients when compared with those of the control group. Glutathione, superoxide dismutase, and catalase activity levels were measured in blood, and these parameters were significantly higher in the control group (p < .001). All results were found to be statistically significant (p < .001). The malondialdehyde level was also found to be significantly higher (p < .01) in the tumour tissue sample. Among the parameters of the tissue antioxidative defense mechanism, superoxide dismutase levels were determined to be significantly higher (p < .001) in the tumour when compared with the levels in adjacent healthy tissue. However, there was no statistically significant difference between the glutathione and catalase activities of the tumour and non-tumour-bearing tissues (p > .05). CONCLUSION: Although the parameters of the oxidative system appear to increase, the antioxidative variants seem to be reduced in laryngeal carcinoma, with one exception: superoxide dismutase has been found in higher amounts in tumour tissue. These results may reflect the effect of oxidative stress in the pathogenesis of laryngeal carcinoma.

The effects of experimental hypothyroidism on hemorheology and plasma fibrinogen concentration.

Effects of hypothyroid on hemorheology of patients had widely attracted the attention of researchers during last decade. The present study has been planned with the purpose to determine the effects of experimental hypothyroidism on hemorheological parameters and fibrinogen concentration. To induce experimental hypothyroid methimazole (75 mg/100 g) was added to the fodder of an experimental group rats for 20 d. After experimental duration, plasma and blood viscosity, hematocrit (Hct), hemoglobin, erythrocyte rigidity index, and plasma fibrinogen concentration values of both the control and the experimental group animals were determined and evaluated. The serum T3 and T4 levels of the experimental group were found lower (p < 0.001) but TSH level higher (p < 0.001) than that of the control group. Plasma viscosity and fibrinogen concentration of hypothyroid group were found significantly higher than controls (p < 0.01). Hematocrit and hemoglobin values were also found lower in the experimental group than the control group animals (p < 0.01). However, there was no significant difference found in blood viscosity at the original Hct value but there was a significant increase at standard Hct value (p < 0.01). There was also no change in erythrocyte rigidity index between control and experimental groups. According to these results it may be said that in hypothyroidism, increased fibrinogen concentration may alter the rheological structure of blood by inducing increase in plasma viscosity.

Erythrocyte osmotic fragility and oxidative stress in experimental hypothyroidism.

The present study was planned to explain the relation between erythrocyte osmotic fragility and oxidative stress and antioxidant statue in primary hypothyroid-induced experimental rats. Twenty-four Spraque Dawley type female rats were divided into two, as control (n = 12) and experimental (n = 12), groups weighing between 160 and 200 g. The experimental group animals have received tap water methimazole added standard fodder to block the iodine pumps for 30 d (75 mg/100 g). Control group animals were fed tap water and only standard fodder for the same period. At the end of 30 d blood samples were drawn from the abdominal aorta of the rats under ether anesthesia. T3, T4, and TSH levels were measured and the animals that had relatively lower T3, T4, and higher TSH levels were accepted as hypothyroid group. Hormone levels of the control group were at euthyroid conditions. Osmotic fragility, as a lipid peroxidation indicator malondialdehyde (MDA), antioxidant defense system indicators superoxide dismutase (SOD) and glutathione (GSH) levels were measured in the blood samples. Osmotic fragility test results: There was no statistically significant difference found between maximum osmotic hemolysis limit values of both group. Minimum osmotic hemolysis limit value of hypothyroid group was found to be higher than that of control group values (p < 0.02). The standard hemolysis and hemolytic increment curve of the hypothyroid group drawn according to osmotic fragility test results was found to be shifted to the right when compared to control group's curve. This situation and hemolytic increment value, which shows maximum hemolysis ratio, is the proof of increased osmotic fragility of the erythrocytes in hypothyroidism. There is no statistically significant difference found between hypothyroid and control groups in the lipid peroxidation indicator MDA and antioxidant indicators SOD and GSH levels. As a result of our study it may be concluded that hypothyroidism may lead to an increase in osmotic fragility of erythrocytes. But the increase in erythrocyte osmotic fragility does not originate from lipid peroxidation.

Changes in hemorheological parameters due to lead exposure in female rats.

Lead is an ubiquitous metal in the environment that induces a broad range of physiological, biochemical and behavioral dysfunctions. The purpose of this study was to investigate its effects on blood parameters and blood viscosity. Female rats (14 Wistar-Albino type) were divided into a control and a lead exposed group. Both groups were fed with the same standard food, but lead acetate was added to the drinking water of the experimental group for 5 weeks. At the end of the experimental period, blood samples were drawn from the abdominal aorta of the anaesthetized animals. Hematocrit (Hct %), hemoglobin (Hb), and the number of erythrocytes were determined, blood viscosity was measured with a rotational viscometer, and the lead concentration in blood was analyzed by means of flame atomic absorption spectrometry. The erythrocyte count, Hb and Hct % of the lead exposed group were found to be significantly lower than in the control group (p<0.01). The blood viscosity level was significantly higher compared to the control group (p<0.01). It can be concluded that increased lead concentrations in blood impair certain hemorheological mechanisms and increase blood viscosity.

Lipid peroxidation and antioxidative enzyme activities in childhood epilepsy.

This study aimed to investigate the relationship among lipid peroxidation, subsequent activation of scavenger enzymes (superoxide dismutase and glutathione peroxidase), and the presence of structural abnormality in 52 epileptic children receiving monotherapy (medically responsive) or polytherapy (medically intractable). Plasma lipid peroxidation in epileptic patients with abnormal magnetic resonance imaging (MRI) findings significantly increased as compared with that of 16 healthy children (P < .05), whereas antioxidant enzymes were not significantly affected. Both medically controlled and intractable children with normal MRI had higher activities of superoxide dismutase than those of controls (P < .05). The activity of superoxide dismutase in epileptic patients with structural abnormality did not significantly change as compared with controls. Activity of glutathione peroxidase in all of the epileptic children was not significantly different from controls. The activity of antioxidant enzymes or plasma malonyldialdehyde levels did not correlate with duration of epilepsy, frequency of seizures (> one seizure per month or not), and the presence or localization (focal, multifocal, or generalized) of electroencephalographic or MRI abnormalities. Increased plasma lipid peroxidation may be causally related to the presence of structural abnormality rather than ongoing epileptic activity or therapy status.