The administration of lithium chloride (LiCl) for cardiac output (CO) measurement via a peripheral instead of a central vein has been described previously as a valid alternative route in pigs and dogs. The aim of the study was to compare CO measurements after administration of LiCl using two peripheral veins, cephalic or jugular, in goats. Ten adult, female, experimental goats undergoing bilateral stifle arthrotomy were recruited for the study. Paired CO measurements were taken two minutes apart during stable conditions in isoflurane-anaesthetised goats. Forty-two paired CO measurements were taken in total, and the median (range) of paired CO measurement per goat were 4.5 (3-6). The mean (SD) CO using the cephalic and jugular vein for injection of LiCl was 5.28 (1.29) L min-1 and 5.20 (1.24) L min-1 respectively. The Bland-Altman analysis showed an acceptable agreement with a mean bias of 1.33% with limits of agreement (LoA) of -18.43 to 21.09%. The percentage of error was 25%. The four-quadrant plot analysis showed a poor agreement (71%) between the two routes. The polar plot showed a poor trending ability. An 86% inclusion rate (18/21 points) was reached with a ± 35° radial sector size. The findings revealed that the agreement between the two routes is not as precise as the authors expected, however the results are comparable with studies published previously.

To explore the role of lithium chloride (LiCl) in Pseudomonas aeruginosa (PA) keratitis.

For decades, lithium chloride (LiCl) has been used as a treatment option for those living with bipolar disorder (BD). As a result, many studies have been conducted to examine its mode of action, toxicity, and downstream cellular responses. We know that LiCl is able to affect cell signaling and signaling transduction pathways through protein kinase C and glycogen synthase kinase-3, which are considered to be important in regulating gene expression at the translational level. However, additional downstream effects require further investigation, especially in translation pathway. In yeast, LiCl treatment affects the expression, and thus the activity, of PGM2, a phosphoglucomutase involved in sugar metabolism. Inhibition of PGM2 leads to the accumulation of intermediate metabolites of galactose metabolism causing cell toxicity. However, it is not fully understood how LiCl affects gene expression in this matter. In this study, we identified three genes, NAM7, PUS2, and RPL27B, which increase yeast LiCl sensitivity when deleted. We further demonstrate that NAM7, PUS2, and RPL27B influence translation and exert their activity through the 5'-Untranslated region (5'-UTR) of PGM2 mRNA in yeast.

Dermacentor reticulatus (Fabr., 1794) (Acari: Ixodidae) is parasite that spreads many diseases which are dangerous to humans and animals. Microelement lithium was found to have promising potential against the detrimental bee pest Varroa destructor. Furthermore, its effectiveness was confirmed against Dermanyssus gallinae, a major parasite of poultry, in vitro. In the present study, we investigated whether the efficacy of lithium chloride extends to other parasitic species, such as D. reticulatus. Our results revealed, for the first time, that the effectiveness of lithium chloride extends to D. reticulatus, confirmed to have 100% mortality at a relatively high minimum concentration of 1.38 M in vitro. The 24 h and 48 h median lethal concentration (LC50) values proved to be 0.654 M and 0.481 M, respectively, for this species. Our pilot study may contribute to a better understanding of the properties of lithium ion. Furthermore, it may elicit further studies aiming to reveal whether the different environmental mineral conditions may influence the D. reticulatus population. Further studies might reveal whether lithium has any possible veterinary relevance.

BACKGROUND We synthetized a 3D printed poly-ε-caprolactone (PCL) scaffold with polydopamine (PDA) coating and lithium chloride (LiCl) deposition for cartilage tissue engineering and analyzed its effect on promoting rabbit bone marrow mesenchymal stem cells (rBMSC) chondrogenesis in vitro. MATERIAL AND METHODS PCL scaffolds were prepared by 3D printing with a well-designed CAD digital model, then modified by PDA coating to produce PCL-PDA scaffolds. Finally, LiCl was deposited on the PDA coating to produce PCL-PDA-Li scaffolds. The physicochemical properties, bioactivity, and biocompatibility of PCL-PDA-Li scaffolds were accessed by comparing them with PCL scaffolds and PCL-PDA scaffolds. RESULTS 3D PCL scaffolds exhibited excellent mechanical integrity as designed. PDA coating and LiCl deposition improved surface hydrophilicity without sacrificing mechanical strength. Li⁺ release was durable and ion concentration did not reach the cytotoxicity level. This in vitro study showed that, compared to PCL scaffolds, PCL-PDA and PCL-PDA-Li scaffolds significantly increased glycosaminoglycan (GAG) formation and chondrogenic marker gene expression, while PCL-PDA-Li scaffolds showed far higher rBMSC viability and chondrogenesis. CONCLUSIONS 3D printed PCL-PDA-Li scaffolds promoted chondrogenesis in vitro and may provide a good method for lithium administration and be a potential candidate for cartilage tissue engineering.

Avian infectious bronchitis (IB) was caused by infectious bronchitis virus (IBV), a coronavirus, which leads to enormous economic losses in the poultry industry. Studies have shown that lithium chloride (LiCl) is a good virus inhibitor. Through cell culture, virus infection, and RT-qPCR, we found that LiCl could down-regulate the apoptosis-related genes Caspase-3 and Bax, up-regulate Bcl-2, and down-regulate the inflammatory-related genes (NF-κB, NLRP3, TNF-α, and IL-1β) via inhibiting virus replication. Finally, clinical trials showed that LiCl could inhibit IBV-induced apoptosis and inflammatory in chicken embryos as well as reduce the mortality and deformity rate of chicken embryos. The results showed that LiCl has antiviral activity against IBV and clinical effects. Further studies are required to explore the exact action mechanism of LiCl on IBV-induced apoptosis and inflammation.

Neurons synthesizing gonadotropin-inhibitory hormone (GnIH) have been implicated in the control of reproduction, food intake and stress. Serotonin (5-HT) receptors have been shown in GnIH neurons; however, their functional role in the regulation of GnIH neurons remains to be elucidated. In this study, we measured intracellular calcium ion levels following 5-HT treatment to hypothalamic primary cultures of enhanced fluorescent green protein-tagged GnIH (EGFP-GnIH) neurons from Wistar rat pups of mixed sex. Three days after initial seeding of the primary cultures, the test groups were pre-treated with lithium chloride to selectively inhibit glycogen synthase kinase 3 beta to promote intracellular calcium levels, whereas the control groups received culture medium with no lithium chloride treatment. 24 h later, the cultures were incubated with rhodamine-2AM (rhod-2AM) calcium indicator dye for one hour prior to imaging. 5-HT was added to the culture dishes 5 min after commencement of imaging. Analysis of intracellular calcium levels in EGFP-GnIH neurons showed that pre-treatment with lithium chloride before 5-HT treatment resulted in significant increase in intracellular calcium levels, two times higher than the baseline. This suggests that lithium chloride enhances the responsiveness of GnIH neurons to 5-HT.

Wnt/β-catenin signaling induced by the Norrin/Frizzled-4 pathway has been shown to improve capillary repair following oxygen induced retinopathy (OIR) in the mouse, a model for retinopathy of prematurity. Here we investigated if treatment with the monovalent cation lithium that has been shown to augment Wnt/β-catenin signaling in vitro and in vivo has similar effects. In cultured human microvascular endothelial cells, LiCl as well as SB 216763, another small molecule that activates Wnt/β-catenin signaling, induced proliferation, survival and migration, which are all common parameters for angiogenic properties in vitro. Moreover, treatment with both agents caused an increase in the levels of β-catenin and their translocation to nuclei while quercetin, an inhibitor of Wnt/β-catenin signaling, completely blocked the effects of LiCl on proliferation. In mice with OIR, intraperitonal or intravitreal treatment with LiCl markedly increased the retinal levels of β-catenin, but did not improve capillary repair. In contrast, repair was significantly improved following intravitreal treatment with Norrin. The effects of LiCl on HDMEC in vitro have minor relevance for OIR in vivo, and the influence of the Norrin/Frizzled-4 pathway on capillary repair in OIR is not reproducible upon enhancing Wnt/β-catenin signaling by LiCl treatment strongly indicating the presence of additional and essential mechanisms.

The poultry red mite (Dermanyssus gallinae) is the main pest of poultry, causing severe problems by being a vector of several animal and human pathogens. The number of miticides is few, and their efficacy in practice implies problems of residues and resistance; therefore, the demand for a new and safe agent is constant. The present publication investigated the effectiveness of lithium chloride under in vitro conditions on poultry red mites. This chemical currently appears to be one of the most promising alternatives to study amongst potential applicants to treat varroosis, a fatal disease of honey bees. In Experiment I, the previously used experimental doses (5.52 M, 2.76 M, 1.38 M) on Varroa mites confirmed their in vitro activity on the poultry red mite. Three event times (uncontrolled movement, immobilisation and death) were recorded to base the response to treatment for each concentration. In Experiment II, the LD 50 value was calculated, i.e., the value at which 50% of the mites were killed by the treatment. This Experiment showed that the LD50 of lithium chloride = 0.265 M in the poultry red mite. It is to note that the study remained restricted to in vitro confirmation of lithium chloride's effectiveness on the parasite. Thus, further extensive studies are needed to decide whether it has any relevance in practice against D. gallinae, and also to assess potential residue problems that could affect poultry products.

Postoperative cognitive dysfunction is a common complication in elderly patients after surgeries involving anesthesia, but the underlying mechanisms are poorly understood. Lithium is a conventional treatment for bipolar disorder, which exerts a neuroprotective role in various diseases by inhibiting glycogen synthase kinase-3β (GSK-3β) in the brain and spinal cord. However, it is not known whether lithium chloride (LiCl) can protect against cognitive dysfunction induced by sevoflurane (SEV) anesthesia. Here, we examined the effects of LiCl on SEV-induced cognitive dysfunction in rats and on SEV-induced neuron apoptosis. We report that anesthesia with SEV significantly impaired memory performance, induced oxidative stress and hippocampal neuron apoptosis, and stimulated GSK-3β activity. Treatment with LiCl ameliorated SEV-induced cognitive disorder in rats by inhibiting the GSK-3β/β-catenin signaling pathway. In addition, LiCl reduced hippocampal neuron apoptosis and oxidative stress induced by SEV anesthesia. These results suggest that LiCl may have potential for development into a therapeutic agent for treatment of SEV anesthesia-induced cognitive dysfunction.

Root resorption is a common side effect of orthodontic treatment. In the current study, lithium chloride (LiCl), a Wnt signaling activator, was examined to determine its effect on root resorption. In total, 10 Sprague Dawley rats were randomly allocated into the experimental group (EG) and control group (CG). Each group consisted of five subjects. By using closed nickel-titanium coil springs, a 50-g force was applied between the upper incisors and the maxillary right first molars in order to mimic orthodontic biomechanics in the EG and CG for 14 days. During the 14 days, the EG rats were gavage-fed 200 mg/kg LiCl every 48 h. Next, digital radiographs were captured using a micro-computational tomography scanner. The movement of the maxillary first molars and the root resorption area ratio were measured electronically on the digital radiographs. The outcomes were analyzed using ANOVA. Following 14 days of experimental force application, all rats had spaces of varying sizes between the first and second right maxillary molars. The average distance measured in the CG was slightly higher than in the EG, however, the difference was not found to be statistically significant (P=0.224). Root resorption craters were observed in the groups following the experiment. Rough cementum areas were observed on the mesial surface of the distobuccal and distopalatal roots. The mean root resorption area ratio of CG was significantly greater than EG (P<0.05). Results of the present study indicate that LiCl can attenuate orthodontically induce root resorption during orthodontic tooth movement. The effect of LiCl on tooth movement is insignificant.

The avian coronavirus infectious bronchitis virus (IBV) is a major economic pathogen of domestic poultry that, despite vaccination, causes mortality and significant losses in production. During replication of the RNA genome there is a high frequency of mutation and recombination, which has given rise to many strains of IBV and results in the potential for new and emerging strains. Currently the live-attenuated vaccine gives poor cross-strain immunity. Effective antiviral agents may therefore be advantageous in the treatment of IBV. Lithium chloride (LiCl) is a potent inhibitor of the DNA virus herpes simplex virus but not RNA viruses. The effect of LiCl on the replication of IBV was examined in cell culture using two model cell types; Vero cells, an African Green monkey kidney-derived epithelial cell line; and DF-1 cells, an immortalized chicken embryo fibroblast cell line. When treated with a range of LiCl concentrations, IBV RNA and protein levels and viral progeny production were reduced in a dose-dependent manner in both cell types, and the data indicated that inhibition was a cellular rather than a virucidal effect. Host cell protein synthesis still took place in LiCl-treated cells and the level of a standard cellular housekeeping protein remained unchanged, indicating that the effect of LiCl was specifically against IBV.

We herein describe a novel procedure for dentin regeneration that mimics the biological processes of tooth development in nature. The canonical Wnt signaling pathway is an important regulator of the Dentin sialophosphoprotein (Dspp) expression. Our approach mimics the biological processes underlying tooth development in nature and focuses on the activation of canonical Wnt signaling to trigger the natural process of dentinogenesis. The coronal portion of the dentin and the underlying pulp was removed from the first molars. We applied lithium chloride (LiCl), an activator of canonical Wnt signaling, on the amputated pulp surface to achieve transdifferentiation toward odontoblasts from the surrounding pulpal cells. MicroCT and microscopic analyses demonstrated that the topical application of LiCl induced dentin repair, including the formation of a complete dentin bridge. LiCl-induced dentin is a tubular dentin in which the pulp cells are not embedded within the matrix, as in primary dentin. In contrast, a dentin bridge was not induced in the control group treated with pulp capping with material carriers alone, although osteodentin without tubular formation was induced at a comparatively deeper position from the pulp exposure site. We also evaluated the influence of LiCl on differentiation toward odontoblasts in vitro. In the mDP odontoblast cell line, LiCl activated the mRNA expression of Dspp, Axin2 and Kallikrein 4 (Klk4) and downregulated the Osteopontin (Osp) expression. These results provide a scientific basis for the biomimetic regeneration of dentin using LiCl as a new capping material to activate dentine regeneration.

LiCl is widely prescribed for bipolar disorder but adversely associated with a higher incidence of increased body weight. Here, we investigated effects and underlying mechanisms of LiCl on lipid accumulation. LiCl induced dose-dependent lipid accumulation in HepG2 and RAW264.7 cells under normal as well as high glucose conditions. LiCl exposure additionally promoted lipid accumulation in livers of zebrafish. SB216763, a specific GSK-3β inhibitor, did not affect lipid accumulation in HepG2 cells. Expression of key lipogenic enzymes, such as FAS and aP2, as well as SR-B1 were increased in RAW264.7 cells. LiCl enhanced FAS, ACC and SCD-1 mRNA levels while suppressing CPT-1 in HepG2 cells. LiCl stimulated DNA binding activities of SREBP-1c and ChREBP. LiCl activated AMPK phosphorylation but the AMPK inhibitor, AICAR, did not suppress LiCl-induced lipid accumulation in RAW264.7. LiCl, but not SB216763, induced a significant increase in ROS in RAW264.7 and HepG2 cells. NOX activity was dose-dependently enhanced by LiCl. Furthermore, NOX-1, NOX-2 and DUOX-1 mRNA levels were upregulated at an early stage of LiCl stimulation. LiCl-induced lipid accumulation was suppressed by the antioxidant, NAC, and inhibitors of NOX, DPI and APO. Phosphorylation and transcriptional activity of CREB were enhanced by LiCl. The cell-permeable cAMP analog, di-butyryl cAMP, not only promoted lipid accumulation itself but also LiCl-induced lipid accumulation in RAW264.7 cells. H-89, a PKA inhibitor, suppressed CREB activation, lipid accumulation and NOX activity in RAW264.7 cells. Our results indicate that LiCl stimulates lipid accumulation in hepatocyte and macrophage cells potentially through increased PKA-dependent ROS production.

Inflammation-mediated skeletal muscle wasting occurs in patients with sepsis and cancer cachexia. Both conditions severely affect patient morbidity and mortality. Lithium chloride has previously been shown to enhance myogenesis and prevent certain forms of muscular dystrophy. However, to our knowledge, the effect of lithium chloride treatment on sepsis-induced muscle atrophy and cancer cachexia has not yet been investigated. In this study, we aimed to examine the effects of lithium chloride using in vitro and in vivo models of cancer cachexia and sepsis. Lithium chloride prevented wasting in myotubes cultured with cancer cell-conditioned media, maintained the expression of the muscle fiber contractile protein, myosin heavy chain 2, and inhibited the upregulation of the E3 ubiquitin ligase, Atrogin-1. In addition, it inhibited the upregulation of inflammation-associated cytokines in macrophages treated with lipopolysaccharide. In the animal model of sepsis, lithium chloride treatment improved body weight, increased muscle mass, preserved the survival of larger fibers, and decreased the expression of muscle-wasting effector genes. In a model of cancer cachexia, lithium chloride increased muscle mass, enhanced muscle strength, and increased fiber cross-sectional area, with no significant effect on tumor mass. These results indicate that lithium chloride exerts therapeutic effects on inflammation-mediated skeletal muscle wasting, such as sepsis-induced muscle atrophy and cancer cachexia.

To gain insight into the basic neurobiological processes regulated by lithium--an effective drug for bipolar disorder--we used Affymetrix Genome Arrays to examine lithium-induced changes in genome-wide gene expression profiles of head mRNA from the genetic model organism Drosophila melanogaster. First, to identify the individual genes whose transcript levels are most significantly altered by lithium, we analyzed the microarray data with stringent criteria (fold change>2; p<0.001) and evaluated the results by RT-PCR. This analysis identified 12 genes that encode proteins with various biological functions, including an enzyme responsible for amino acid metabolism and a putative amino acid transporter. Second, to uncover the biological pathways involved in lithium's action in the nervous system, we used less stringent criteria (fold change>1.2; FDR<0.05) and assigned the identified 66 lithium-responsive genes to biological pathways using DAVID (Database for Annotation, Visualization and Integrated Discovery). The gene ontology categories most significantly affected by lithium were amino acid metabolic processes. Taken together, these data suggest that amino acid metabolism is important for lithium's actions in the nervous system, and lay a foundation for future functional studies of lithium-responsive neurobiological processes using the versatile molecular and genetic tools that are available in Drosophila.

Lithium compounds, a classic class of metal complex medicine that target GSK 3β and are widely known as mood-stabilizer, have recently been reported as potential anti-tumor drugs. The objective of this investigation was to explore the anticancer potential of lithium chloride (LiCl) and elucidate its mode of action in pancreatic cancer cells. The MTT, colony formation, and Edu assay were used to evaluate the impact of LiCl on pancreatic cancer cell proliferation. Various methods were employed to investigate the anti-tumor activity of LiCl and its underlying mechanisms. Cell cycle analysis and apoptosis detection assays were utilized for in vitro experiments, while the orthotopic pancreatic cancer mouse model was employed to evaluate the effectiveness of LiCl treatment in vivo. Furthermore, the impact of LiCl on the proliferation of patient-derived organoids was also studied. The results demonstrated that LiCl inhibited the proliferation of pancreatic cancer (PC) cells, induced G2/M phase arrest, and activated apoptosis. Notably, the triggering of endoplasmic reticulum (ER) stress by LiCl was observed, leading to the activation of the PERK/CHOP/GADD34 pathway, which subsequently promoted apoptosis in PC cells. In the future, Lithium compounds could become an essential adjunct in the treatment of human pancreatic cancer.

Zebrafish provide researchers and students alike with an excellent model of vertebrate nervous system development due to a high degree of conserved developmental mechanisms and transparent embryos that develop in synchrony. In these laboratory exercises, undergraduate students explore cell biological concepts while performing hypothesis-driven novel research utilizing methodologies such as immunofluorescence, confocal microscopy, image analysis, pharmacology, and basic statistics. In the first block of exercises, students perform anti-acetylated tubulin (anti-AT) immunofluorescence, identify spinal tracts and neuronal subtypes, and perform conventional and confocal microscopy. Building on knowledge acquired in the first block of exercises, during the second block, students subsequently perform pharmacological activation of Wnt signaling through lithium chloride treatments, and assess nervous system integrity through anti-AT immunofluorescence. Students perform various quantitative methods and apply statistics to determine outcomes of Wnt activation. In their final laboratory report, students contextualize their results with foundations of molecular mechanisms of nervous system development. In sum, these exercises offer undergraduate students a model of independent research at the graduate level.

Transmissible gastroenteritis virus (TGEV) is a porcine coronavirus. Lithium chloride (LiCl) has been found to be effective against several DNA viruses, such as Herpes simplex virus and vaccinia virus. Recently, we and others have reported the inhibitory effect of LiCl on avian infectious bronchitis coronavirus (IBV) infection, an RNA virus. In the current study, the action mechanism of LiCl on cell infection by TGEV was investigated. Plaque assays and 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenyl tetrazoliumbromide (MTT) assays showed that the cell infection by TGEV was inhibited in a dose-dependent manner, when LiCl was added to virus-infected cells; the cell infection was not affected when either cells or viruses were pretreated with the drug. The inhibition of TGEV infection in vitro by LiCl was observed at different virus doses and with different cell lines. The inhibitory effect of LiCl against TGEV infection and transcription was confirmed by RT-PCR and real-time PCR targeting viral S and 3CL-protease genes. The time-of-addition effect of the drug on TGEV infection indicated that LiCl acted on the initial and late stage of TGEV infection. The production of virus was not detected at 36 h post-infection due to the drug treatment. Moreover, immunofluorescence (IF) and flow cytometry analyses based on staining of Annexin V and propidium iodide staining of nuclei indicated that early and late cell apoptosis induced by TGEV was inhibited efficiently. The ability of LiCl to inhibit apoptosis was investigated by IF analysis of caspase-3 expression. Our data indicate that LiCl inhibits TGEV infection by exerting an anti-apoptotic effect. The inhibitory effect of LiCl was also observed with porcine epidemic diarrhea coronavirus. Together with other reports concerning the inhibitory effect of lithium salts on IBV in cell culture, our results indicate that LiCl may be a potent agent against porcine and avian coronaviruses.

This study evaluated the ability of lithium chloride (LiCl) to increase bone filling (BF) around threaded titanium implants inserted in estrogen-deficient rats and, thein-vitro effects of this drug on osteoblast-like cell viability, proliferation, mineralization and expression of bone-related markers.