No abstract available.
Lithium Chloride* ; Lithium*

OBJECTIVE: The present study was designed to identify the stress-induced polyamine (PA) response and its modulation by chronic treatment of lithium in brain (hippocampus) and periphery (liver). METHOD: For immobilization stress, rats (230-250 g, male) were placed in restrainer once daily, for 3h. All biochemical measurements were done 5h after the beginning of immobilization stress application. Stress application was done for 5 days and, after a resting interval of 7 days, rats were subjected to an additional stress. Additional groups were subjected to same stress schedule, but during the 7 day interval, one group received once daily injections of 2.5 mmol/kg lithium chloride subcutaneously, and other received saline. RESULTS: The putrescine (PU) level was increased after each stress episode. After cessation of the intermittent stress period, an additional stress 7 days later led again to an increase in PU level in brain but not in liver. The later increase in PU level was blocked by lithium treatment during the intervening 7 day interval between stressors. CONCLUSION: The results suggest that long-term lithium treatment can inhibit an overreactive PA response in brain. So, maladjustment of a stress induced PA response may be a factor to the affective illness and can be target of lithium.
Animals ; Appointments and Schedules ; Brain* ; Immobilization ; Lithium Chloride ; Lithium* ; Liver ; Putrescine ; Rats

Lithium has long been a primary drug used to treat bipolar mood disorder. Recently, in vivo and in vitro studies have demonstrated neuroprotective actions of lithium, even though therapeutic mechanisms of lithium remain obscure. The present study was undertaken to examine whether pretreatment with lithium can reduce the expression of aquaporin4 (AQP4) related to brain edema. Chronic lithium treatment was produced by pellet of standard diet containing 40 mmol/dL and/or 60 mmol/dL lithium chloride for 25 days. The serum concentrations of lithium were increased to 0.60+/-0.1 mEq/L in the 40 mM/dL and 60 mM/dL lithium treated rats which is therapeutic dose of clinical practice. After chronic lithium treatment, there was a dose-dependent down-regulation of AQP4 expression in the cerebrospinal fluid-brain interfaces and blood brain barrier. Down-regulation of AQP4 after chronic lithium treatment suggest that lithium may be used for the prevention or treatment of brain edema.
Animals ; Aquaporin 4* ; Blood-Brain Barrier ; Brain Edema ; Brain* ; Diet ; Down-Regulation* ; Lithium ; Lithium Chloride ; Mood Disorders ; Rats*

OBJECTIVES: Mechanisms of clinical synergistic effects, induced by co-treatments of lithium and valproate, are unclear. Extracellular signal-regulated kinase (ERK) has been suggested to play important roles in mechanisms of the action of mood stabilizers. In this study, effects of co-treatments of lithium and valproate on the ERK1/2 signal pathway and its down-stream transcription factors, ELK1 and C-FOS, were investigated in vitro. METHODS: PC12 cells, human pheochromocytoma cells, were treated with lithium chloride (30 mM), valproate (1 mM) or lithium chloride + valproate. The phosphorylation of ERK1/2 was analyzed with immunoblot analysis. Transcriptional activities of ELK1 and C-FOS were analyzed with reporter gene assay. RESULTS: Single treatment of lithium and valproate increased the phosphorylation of ERK and transcriptional activities of ELK1 and C-FOS, respectively. Combined treatments of lithium and valproate induced more robust increase in the phosphorylation of ERK1/2 and transcriptional activities of ELK1 and C-FOS, compared to those in response to single treatment of lithium or valproate. CONCLUSIONS: Co-treatments of lithium and valproate induced synergistic increase in the phosphorylation of ERK1/2 and transcriptional activities of its down-stream transcription factors, ELK1 and C-FOS, compared to effects of single treatment. The findings might suggest potentiating effects of lithium and valproate augmentation treatment strategy.
Animals ; Genes, Reporter ; Humans ; Lithium Chloride ; Lithium* ; PC12 Cells* ; Pheochromocytoma ; Phosphorylation* ; Phosphotransferases ; Signal Transduction ; Transcription Factors ; Valproic Acid*

Glycogen synthase kinase (GSK)-3β and related enzymes are associated with various forms of neuroinflammation, including spinal cord injury (SCI). Our aim was to evaluate whether lithium, a non-selective inhibitor of GSK-3β, ameliorated SCI progression, and also to analyze whether lithium affected the expression levels of two representative GSK-3β–associated molecules, nuclear factor erythroid 2-related factor-2 (Nrf-2) and heme oxygenase-1 (HO-1) (a target gene of Nrf-2). Intraperitoneal lithium chloride (80 mg/kg/day for 3 days) significantly improved locomotor function at 8 days post-injury (DPI); this was maintained until 14 DPI (P<0.05). Western blotting showed significantly increased phosphorylation of GSK-3β (Ser9), Nrf-2, and the Nrf-2 target HO-1 in the spinal cords of lithium-treated animals. Fewer neuropathological changes (e.g., hemorrhage, inflammatory cell infiltration, and tissue loss) were observed in the spinal cords of the lithium-treated group compared with the vehicle-treated group. Microglial activation (evaluated by measuring the immunoreactivity of ionized calcium-binding protein-1) was also significantly reduced in the lithium-treated group. These findings suggest that GSK-3β becomes activated after SCI, and that a non-specific enzyme inhibitor, lithium, ameliorates rat SCI by increasing phosphorylation of GSK-3β and the associated molecules Nrf-2 and HO-1.
Animals ; Blotting, Western ; Glycogen Synthase Kinases ; Glycogen Synthase* ; Glycogen* ; Heme Oxygenase-1* ; Heme* ; Hemorrhage ; Lithium Chloride ; Lithium* ; Phosphorylation ; Rats* ; Spinal Cord Injuries* ; Spinal Cord*

OBJECTIVE: The aim of the study was to investigate whether lithium chloride and medroxyprogesterone acetate can potentiate the cytotoxicity of imatinib mesylate in human endometrial cancer in vitro and the effect of midkine in these therapies. METHODS: Imatinib mesylate (50 microM), lithium chloride (100 microM), medroxyprogesterone acetate (200 microM) and their combination were applied to monolayer and three dimensional cultures of human Ishikawa endometrial cancer for 72 hours. The cell proliferation index, apoptotic index, caspase-3 and midkine levels, cell cycle distributions in monolayer cultures and cell ultrastructure in spheroid cultures were evaluated. Results were statistically analyzed using the Student's t-test. RESULTS: All drug applications inhibited cell proliferation (p<0.05), however the combination were the effective groups for 72 hours (p<0.05). Interestingly, although the loss of efficiency was seen higly seen every 24 hours at single applications, the inhibition rates of the combination groups were almost same for 72 hours. In concordance with these results, the apoptotic index, caspase-3 levels (p<0.05), cell morphology and ultrastructure damages were much higher in the combination groups. Imatinib mesylate induced S-phase arrest, however other groups induced G0+G1-phase arrest at 24 hours and all groups induced G0+G1 arrest at 72 hours (p<0.05). Imatinib mesylate and imatinib mesylate with medroxyprogesterone acetate induced highest decrease in midkine levels, respectively (p<0.05). CONCLUSION: The present study showed that the combination of imatinib mesylate with lithium chloride and medroxyprogesterone acetate is highly active in Ishikawa endometrial carcinoma in vitro and the inhibition of midkine involved in their mechanism of action against endometrium defense.
Benzamides ; Caspase 3 ; Cell Cycle ; Cell Proliferation ; Cytokines ; Endometrial Neoplasms ; Endometrium ; Female ; Humans ; Imatinib Mesylate ; Lithium ; Lithium Chloride ; Medroxyprogesterone ; Medroxyprogesterone Acetate ; Mesylates ; Piperazines ; Pyrimidines

Lithium salts are being used increasingly to treat patient with affective disorders, especially acute mania, or bipolar manic-depressive illness. For therapeutic effect the lithium content must be maintained at or above a particular level. Lithium poisoning due to overdosage may be seen occasionally, and its course is determined primarily by the rate of renal lithium elimination. A search is therefore indicated for procedures that could raise the lithium clearance. In a number of reports renal lithium excretion has been studied in relation to the excretion of water, sodium, potassium and hydrogen, but effects of sodium or water on the lithium excretion has not yet been clarified. Hence the present study was undertaken to investigate the effects of corticosteroid on the excretion of lithium ion. The female rat (Sprague-Dowley), weighing from 200 to 300g, was injected with 50mg/kg of lithium chloride intraperitoneally, and then injected with graded dosage of fludrocortisones and dexamethasone in each group. During the injected rats were incubated in metabolic cage, 24 hour urine of rats were collected. At 24 hours after injection, the rats were sacrificed with guillotine, the blood were collected. And then the concentrations of Na⁺, K⁺, Li⁺ of collected urine and serum were checked by Flame photometer. The results are summarized as follows 1. Fludrocortisone decreased the serum concentration of lithium and increased the urinary excretion of lithium. 2. In the group treated with low dose of dexamethasone (0.1 mg/kg), the serum concentration of lithium was decreased and high dose of dexamethasone (1 mg/kg) increased the urinary excretion of lithium. 3. Fludrocortisone increased the urinary [Na⁺]/[K⁺] in serum and decreased [Na⁺]/[K⁺] inurine, but opposite effects were occurred in dexamethasone. By above results, it may be concluded that corticosteroid increased the urinary excretion of lithium and decreased the serum concentration of lithium, but it seems to be there in no relationship between these effects of corticosteroid and of the renal Na⁺ or K⁺ transport.
Adrenal Cortex Hormones* ; Animals ; Bipolar Disorder ; Dexamethasone ; Female ; Fludrocortisone ; Humans ; Hydrogen ; Lithium Chloride ; Lithium* ; Mood Disorders ; Poisoning ; Potassium ; Rats ; Renal Elimination* ; Salts ; Sodium ; Water

PURPOSE: To examine the putative seizure-protective properties of ketamine in lithium-pilocarpine induced status epilepticus (LPSE). METHODS: Lithium chloride followed 24 h later by pilocarpine was administered for seizure induction. Ketamine (40 mg/kg) or phenytoin (50 mg/kg) was injected intraperitoneally 10 min or 60 min after the onset of continuous ictal discharge. Then the seizure behavior and EEG were observed and histological changes were compared through Nissl stain at 72 hours. RESULTS: The antiepileptic effect of ketamine, injected during the early stages of LPSE (10 min after the onset of continuous ictal discharge), was comparable to that of phenytoin. Ketamine was more effective than phenytoin in decreasing spike frequency, when administered on the plateau of LPSE (injection 60 min after onset of continuous ictal discharge electrographically). Anticonvulsant action of ketamine was confirmed by a less neuronal injury in hippocampus compared with control rats injected with phenytoin. CONCLUSIONS: In prolonged status epilepticus rat model, ketamine was effective as an antiepileptic, but phenytoin was not. Ketamine was also neuroprotective on the neuronal injury in the hippocampus. These results suggest that ketamine might be useful as an antiepileptic drug when standard antiepileptic drugs fail in the treatment of the refractory cases of status epilepticus.
Animals ; Anticonvulsants ; Electroencephalography ; Hippocampus ; Ketamine* ; Lithium Chloride ; Models, Animal* ; Neurons ; Neuroprotective Agents* ; Phenytoin ; Pilocarpine ; Rats* ; Seizures ; Status Epilepticus*

OBJECTIVETo observe the effects of lithium chloride combined with human umbilical cord blood mesenchymal stem cell (hUCB-SCs) transplantation in the treatment of spinal cord injury in rats.

METHODSEighty female SD rats with complete T9 spinal cord transaction were randomized into 4 groups (n=20), namely the control group (group A), lithium chloride group (group B), hUCB-SCs group (group C) and hUCB-SCs(+) lithium chloride group (group D). On days 1 and 3 and the last days of the following weeks postoperatively, the motor function of the hindlimb of the rats were evaluated according to the BBB scores. At 8 weeks, all the rats were sacrificed and the spinal cords were taken for morphological observation. The spinal cord tissues at the injury site were observed with Brdu nuclear labeling to identify the survival and migration of the transplanted SCs. The regeneration and distribution of the spinal nerve fibers were observed with fluorescent-gold (FG) spinal cord retrograde tracing.

RESULTSBrdu labeling showed that the transplanted hUCB-SCs survived and migrated in the spinal cord 8 weeks postoperatively in groups C and D. FG retrograde tracing identified a small amount of pyramidal cells that migrated across the injury site in groups C and D. The BBB scores of the hindlimb motor function 8 weeks postoperatively were 4.11∓0.14, 4.50∓0.15, 8.31∓0.11 and 11.15∓0.18 in groups A, B, C and D, respectively.

CONCLUSIONLithium chloride can promote the survival and differentiation of hUCB-SCs into neural cells at the injury site. Lithium chloride combined with hUCB-SCs transplantation may accelerate functional recovery of the hindlimbs in rats with complete transection of the spinal cord.

Animals ; Cord Blood Stem Cell Transplantation ; Female ; Humans ; Lithium Chloride ; therapeutic use ; Rats ; Spinal Cord Injuries ; therapy

OBJECTIVETo investigate the changes in the functional activity of glycogen synthase kinase-3 (GSK-3) in the hepatic tissue after endotoxin (lipopolysaccharide, LPS) tolerance and explore the effects of LPS-induced GSK-3 inhibition on glycogen metabolism in the liver.

METHODSMale SD rats were randomly divided into normal control, endotoxin pretreatment and GSK-3 inhibitor (lithium chloride) groups with corresponding pretreatments prior to a large dose of LPS challenge (10 mg/kg) to induce liver injury. Glycogen deposition and content in the hepatic tissue was detected using periodic acid-Schiff (PAS) staining and a glycogen quantification kit, respectively. Western blotting was performed for semi-quantitative analysis of protein level and inhibitory phosphorylation of GSK-3, and a Coomassie brilliant blue G-250-based colorimetric assay was used to detect calpain activity in the liver.

RESULTSGlycogen content in the liver decreased significantly after LPS challenge in all the 3 groups (P<0.05) but showed no significant difference among the groups (P>0.05). Both LPS and lithium chloride pretreatments caused a significant increase of liver glycogen content (P<0.05). LPS pretreatment induced inhibitory phosphorylation of GSK-3β (P<0.05) and partial cleavage of GSK-3α but did not affect the expression of GSK-3 protein (P>0.05). Large-dose LPS challenge significantly increased the activity of calpain in the liver tissue (P<0.05) to a comparable level in the 3 groups (P>0.05).

CONCLUSIONEndotoxin pretreatment induces inhibitory phosphorylation of GSK-3β and partial cleavage of GSK-3α and promotes the deposition of liver glycogen but does not affect the activity of calpain, which may contribute to an increased glycogen reserve for energy supply in the event of large-dose LPS challenge.

Animals ; Calpain ; metabolism ; Glycogen ; metabolism ; Glycogen Synthase Kinase 3 ; antagonists & inhibitors ; metabolism ; Lipopolysaccharides ; adverse effects ; Lithium Chloride ; pharmacology ; Liver ; drug effects ; metabolism ; pathology ; Male ; Rats ; Rats, Sprague-Dawley