Lithium Exposure Research Articles

Potential link between vaping and hypothyroidism: A case report

Background: Vaping has gained popularity as an alternative to traditional smoking, but its potential health effects, particularly on endocrine function, remain under-explored. This case report highlights a possible association between vaping and the development of subclinical hypothyroidism in a young adult female. Case Presentation: A 25-year-old female with a history of vaping for 30 minutes daily over the course of one year presented with symptoms of fatigue, weight gain, and dry skin. Initial thyroid function tests showed elevated TSH (5.08 uIU/mL), reduced T3 (64 ng/dL), and T4 (4.8 ug/dL), consistent with subclinical hypothyroidism. After discontinuing or reducing vaping, repeat thyroid function tests revealed an improvement in thyroid hormone levels (TSH: 4.69 uIU/mL, T3: 136.4 ng/dL, T4: 5.77 ug/dL) and symptom relief. The use of a vaping device with a lithium-ion battery raised concerns about possible lithium exposure, a known factor in thyroid dysfunction. Conclusion: This case suggests a potential reversible association between vaping and subclinical hypothyroidism, possibly exacerbated by lithium toxicity from battery leakage. Further research is necessary to understand the mechanisms behind vaping-related thyroid dysfunction and the potential role of lithium in this process.

Drug-drug interactions of empagliflozin and dapagliflozin

Abstract Introduction The sodium glucose co-transporter2-inhibitors dapagliflozin (Dapa) and empagliflozin (Empa), initially developed as antihyperglycemic agents, are increasingly also prescribed for non-diabetic patients with heart failure (HF). Glucuronidation by uridine-diphosphate glucuronosyltransferase (UGT)1A9 is the main mechanism of metabolism of Dapa, whereas Empa is eliminated mainly by excretion. Both Dapa and Empa are substrates of P-glycoprotein. The risk for drug-drug interactions (DDI) of Empa and Dapa is assumed to be low. Aim of this study was to summarize reports of DDI of Empa and Dapa from the literature. Methods Search-terms in PubMed were "drug-drug interaction" and AND "sodium glucose co-transporter2-inhibitors" OR "SGLT2" OR "dapagliflozin" OR "empagliflozin". The drugs were classified according the Anatomical Therapeutic Chemical (ATC) system. Included were randomized trials, pharmacovigilance studies, case series, case reports, studies in healthy subjects and in vivo data. The funding of the study and the disclosures of the authors were registered. Results In 45 reports DDI of Empa and Dapa with 29 drugs were described (Table). According to the ATC system, these were drugs for the alimentary tract and metabolism (n=5), blood and blood forming organs (n=2), cardiovascular system (n=11), genitourinary system and sex hormones (n=2), antiinfectives (n=2), antineoplastic and immunomodulating agents (n=3), musculo-skeletal system (n=2) and nervous system (n=2). The reports comprised studies in healthy subjects (n=28), case reports (n=7), case series (n=6), pharmacovigilance studies (n=2), a subgroup analysis of a randomized trial (n=1) and in vivo data (n=1). Most of the reports found no clinically relevant DDI (n=32). Dapa and Empa both had a synergistic diuretic effect with bumetanide, and led to severe infections when combined with the interleukin-17-inhibitors secukinumab or ixekizumab. Empa administered with intravenous iron was reported to increase cell-iron availability, with lithium to reduce lithium exposure and with valproate to increase valproate exposure. Dapa administered with sacubitril-valsartan was reported to lead to severe hypotension, with linezolid to pancytopenia, with donafenib to an increased exposure to donafenib, with rifampicin to a reduction and mefenamic acid to an increase in Dapa exposure. Of the 45 reports, 33 were funded by a pharmaceutical company marketing Dapa or Empa and 33 had authors with conflicts of interest with pharmaceutical companies marketing Dapa or Empa. Conclusions Most data about DDI of Empa and Dapa derive from studies in healthy subjects and from the marketing companies. The clinical relevance DDI of Empa and Dapa in polymorbid patients with polymedication is largely unknown. There is an urgent need for independent studies on DDI of these drugs in diabetic and non-diabetic patients with HF.Table

Retrospective Review of Postpartum Lithium Use Including During Lactation.

Introduction: Lithium remains a gold standard treatment for bipolar disorder including during peripartum. Historically, guidelines advised against breastfeeding while taking lithium though recent data suggest it is acceptable for a healthy infant. Lack of awareness of acceptability contributes to decreased patient and clinician comfort and low breastfeeding rates. We report current breastfeeding rates, monitoring practices, and infant outcomes with lithium exposure in breastmilk at our institution. Methods: A retrospective chart review was conducted at a single academic medical center using records from 2013 to 2023. Electronic medical records were queried to identify patients prescribed lithium postpartum. Data were collected on timing of lithium initiation, lithium dose and concentration, breastfeeding status, and infant outcomes. Results: A total of 18 cases of lithium use in the postpartum period were identified. A total of 39% (n = 7) of patients taking lithium postpartum breastfed. Most patients, 61% (n = 11), initiated lithium prior to pregnancy, 11% (n = 2) initiated during pregnancy and 27% (n = 5) started postpartum. Four infant charts were reviewed with no reports of adverse events. Of these infants, average maternal lithium dose was 750 mg daily, with an average maternal serum lithium concentration of 0.62 mmol/L and average infant serum lithium concentration of 0.16 mmol/L. Conclusion: Our data demonstrate most patients using lithium postpartum have been taking lithium long-term and are not breastfeeding. Lithium exposure in breastmilk appears to be tolerated by healthy infants. There is a need for ongoing research and education on acceptability and infant monitoring recommendations to support patients who would like to breastfeed while on lithium.

Understanding the effects of lithium exposure on castor bean (Ricinus communis) plants, a potential bioindicator of lithium-contaminated areas.

As lithium (Li) stands out as a crucial component of batteries, the inappropriate disposal of electronic gadgets might drive Li pollution in environmentally sensitive environments, such as dumps, where castor bean (Ricinus communis) plant communities are usually found. The exposure to high Li concentration is potentially harmful to the environment and humans. Therefore, it is opportune to evaluate the potential of bioindicator species to monitor Li contamination. In this scenario, the present study assessed the effects of Li exposure on the development of castor bean plants exposed to lithium chloride at five Li dosages (0, 5, 10, 20, and 30mgdm-3). Significant symptoms of phytotoxicity were observed at all doses. Li dosage exhibited increasing impairment effects on plant biometrics, such as stem diameter and the number of leaves, as well as on the SPAD index, nutritional balance, and biomass production. Our findings suggest castor bean as a potential model species for biomonitoring Li-contaminated areas.

#2333 Risk of NDI and CKD in individuals treated with lithium

Abstract Background and Aims Nephrogenic diabetes insipidus (NDI) is a known side effect of lithium treatment. Lithium has also been associated with the development of chronic kidney disease (CKD). The aims of this study were to examine the risk factors for NDI among persons on lithium treatment and the association of NDI and other risk factors with the development of chronic kidney disease (CKD). Method This was a retrospective cohort study of all persons in Iceland using lithium in the years 2003-2018. Lithium exposure was defined as at least one lithium prescription or at least one serum lithium measurement with a detectable lithium level. Patients with affective disorders (ICD-10 codes F30-F39) attending the outpatient clinics of Landspitali–The National University Hospital Mental Health Services in 2014-2016, without lithium exposure, served as controls. NDI was defined as concomitant serum sodium (SNa) >144 mmol/L and urine specific gravity (SG) <1.005; individuals with no SNa measurement after 2003 were excluded from the analysis. CKD stages 3-5 were defined according to the KDIGO guidelines for CKD as estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2. The eGFR was calculated from serum creatinine (SCr) using the CKD-EPI equation. The analysis of incident CKD was limited to the period when standardized SCr measurements had become available, in 2008-2018. Individuals with <2 SCr measurements after 2008 and those with CKD stages 3-5 before 2008 were excluded. In addition, this analysis specifically examined the relationship between the mean serum lithium concentration and the development of CKD, comparing those not exposed to lithium to 3 groups of lithium users with a mean serum lithium concentration of 0.3-0.59, 0.6-0.79 and 0.8-0.99 mmol/L. Acute kidney injury (AKI) was defined according to the SCr component of the KDIGO criteria for AKI, and other comorbid conditions were defined based on ICD-9 and ICD-10 diagnosis codes. Multivariable Cox regression with time-dependent covariables was used for risk assessment. Results In the analysis of the development of NDI, the group exposed to lithium consisted of 2252 individuals, of whom 58 (2.6%) met the criteria for NDI compared with 13 (1.0%) of the 1272 controls. When compared with those without lithium exposure. the risk of NDI was lithium concentration dependent, with a hazard ratio (HR) of 1.22 (95% CI, 0.50–2.98), 5.52 (95% CI, 2.81–10.85) and 10.03 (95% CI, 4.51–22.27) for groups with a mean lithium concentration of 0.3–0.59, 0.6–0.79 and 0.8–0.99 mmol/L, respectively. A previous diagnosis of CKD was also a significant risk factor (HR 3.00 [95% CI, 1.50–6.12]). In the CKD analysis, the group of lithium users comprised 1401 individuals. Of those, 192 (13.7%) developed CKD, compared with 39 (2.8%) of the 1406 controls. Analysis adjusted for initial eGFR showed that NDI was a significant risk factor for CKD (HR 1.90 [95% CI, 1.03-3.54]). Other significant risk factors were mean lithium concentration with HR of 1.25 (95% CI, 0.82–1.91), 2.84 (95% CI, 1.94–4.15) and 5.11 (95% CI, 3.22–8.07) for the groups with a mean lithium concentration of 0.6–0.79 and 0.8–0.99 mmol/L, respectively. Other significant risk factors were age per year (HR 1.03 [95% CI, 1.02–1.05]), diabetes (HR 1.62 (95% CI, 1.08–2.46]) and history of AKI (HR 1.92 [95% CI, 1.33–2.77]). Conclusion Lithium use is associated with NDI in a concentration-dependent manner. Long-term lithium treatment is associated with a risk of CKD, which also is concentration dependent, in patients with bipolar and unipolar mood disorders. NDI may be an important risk factor for CKD.

Lithium levels in drinking water predicted the ratio of attempted to completed suicides in regions with high incidence of affective disorders: Insights from ecological study

IntroductionLithium has demonstrated significant antisuicidal effects: it significantly reduces the high excess overall mortality of patients with affective disorders. MethodsPublic drinking water samples were collected in 53 Lithuanian municipalities during a two-month period. Linear models used lithium level in public drinking water as predictor and ratio of suicide attempts to suicide mortality as outcomes across the municipalities. ResultsLithium in drinking water predicted the ratio of attempted to completed suicides (A/S) nonlinearly, described by a U-shaped curve. The curves for visualization of the association of incidence of affective disorders and suicide standard mortality rate with lithium level displayed significant suicide curve decrements and invers direction in affective disorders curve. Multivariate regression model for ratio A/S in high lithium exposure group (> 7 µg/L, N = 26) suggests that the lithium level can explain 54.3 % of variance of ratio A/S in municipalities with exposure of lithium above median and with high incidence of affective disorders. ConclusionsThe findings provide confirmatory evidence that in municipalities with high incidence of affective disorders higher lithium levels in the public drinking water are associated with higher ratio A/S due to an unchanging number of suicide attempts and due to decreasing suicide lethal outcomes. LimitationsNevertheless, the methods employed detected several factors with well-established associations with suicide. Finally, cohort, prospective or intervention studies are needed to verify the causal inverse relationship of these variables and to speculate the mechanism for this relationship.

Serious adverse drug events associated with psychotropic treatment of bipolar or schizoaffective disorder: a 17-year follow-up on the LiSIE retrospective cohort study.

Mood stabilisers and other psychotropic drugs can lead to serious adverse drug events (ADEs). However, the incidence remains unknown. We aimed to (a) determine the incidence of serious ADEs in patients with bipolar or schizoaffective disorders, (b) explore the role of lithium exposure, and (c) describe the aetiology. This study is part of the LiSIE (Lithium-Study into Effects and Side Effects) retrospective cohort study. Between 2001 and 2017, patients in the Swedish region of Norrbotten, with a diagnosis of bipolar or schizoaffective disorder, were screened for serious ADEs to psychotropic drugs, having resulted in critical, post-anaesthesia, or intensive care. We determined the incidence rate of serious ADEs/1,000 person-years (PY). In 1,521 patients, we identified 41 serious ADEs, yielding an incidence rate of 1.9 events per 1,000 PY. The incidence rate ratio (IRR) between ADEs with lithium present and causally implicated and ADEs without lithium exposure was significant at 2.59 (95% CI 1.20-5.51; p = 0.0094). The IRR of ADEs in patients <65 and ≥65 years was significant at 3.36 (95% CI 1.63-6.63; p = 0.0007). The most common ADEs were chronic lithium intoxication, oversedation, and cardiac/blood pressure-related events. Serious ADEs related to treatment of bipolar (BD) or schizoaffective disorder (SZD) were uncommon but not rare. Older individuals were particularly at risk. The risk was higher in individuals exposed to lithium. Serum lithium concentration should always be checked when patients present with new or unclear somatic symptoms. However, severe ADEs also occurred with other mood stabilisers and other psychotropic drugs.

Serum Lithium Concentration and the Risk of Chronic Kidney Disease

IntroductionLithium is an important treatment option for individuals with mood disorders, but its use has been linked to the development of chronic kidney disease (CKD). Existing studies on this association have reported conflicting results.ObjectivesThe aim of this study was to examine the risk of developing CKD with lithium use adjusting for common comorbidities.MethodsThis was a retrospective cohort study that included all individuals in Iceland receiving lithium therapy between 2008 and 2018. Lithium use was defined as at least one dispensed prescription for Lithium or at least one serum lithium concentration above the detection limit. Patients with affective disorders (ICD-10 codes F30-F39) attending the outpatient clinics of Landspitali–The National University Hospital Mental Health Services in 2014-2016, without lithium exposure, served as controls. CKD stages 3-5 were defined according to the Kidney Disease Improving Global Outcomes (KDIGO) guidelines for CKD as estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2. The eGFR was calculated using the serum creatinine (SCr) based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Acute kidney injury (AKI) was defined according to the SCr component of the KDIGO criteria for AKI, and other comorbid diseases were defined based on ICD-9 and ICD-10 codes. Individuals with fewer than 2 SCr measurements during the study period and those with CKD stages 3-5 prior to 2008 were excluded. Cox regression analysis with time dependent variables was performed to assess the risk of CKD.ResultsThe study included 2046 individuals exposed to lithium, of whom 221 (10.9%) developed CKD in the study period. Among the 1220 control subjects, 39 (3.2%) developed CKD. Lithium use was associated with CKD (hazard ratio [HR] 1.93, 95% confidence interval [CI] 1.37–2.74) after adjusting for sex, age, and comorbid diseases. Other significant risk factors were age (per year, HR 1.03, 95% CI 1.02–1.04), initial eGFR (per mL/min/1.73 m2, HR 0.92-0.96, 95% CI 0.90–0.99), presence of diabetes (HR 1.73, 95% CI 1.15–2.48) and history of AKI (HR 1.89, 95% CI 1.32–2.70). When compared to the control group not exposed to lithium, the risk (HR) of CKD was 1.24 (95% CI 0.81–1.89), 2.88 (95% CI 1.97–4.20) and 5.23 (95% CI 3.31-8.26) for groups with a mean lithium concentration of 0.3-0.59, 0.6-0.79 and 0.8-0.99 mmol/L, respectively.ConclusionsLong-term lithium therapy seems to increase the risk of CKD in a concentration-dependent manner in individuals with bipolar and unipolar mood disorders. To mitigate this risk, it is essential to monitor blood levels carefully and use doses of lithium as low as possible for adequate mood stabilization and treatment.Disclosure of InterestNone Declared

Lithium nephropathy in Bipolar Disorder: a clinical challenge

IntroductionLithium nephropathy can occur in long-term lithium-treated bipolar disorder patients. Key risk factors include duration of lithium exposure, cumulative dose, acute intoxication episodes, advanced age, and comorbidities such as hypertension, diabetes mellitus, hyperparathyroidism, and hyperuricemia, along with concurrent use of antipsychotics. The clinical presentation is gradual, with mild proteinuria, often accompanied by arginine vasopressin resistance. Histological studies show a correlation between interstitial fibrosis and cumulative lithium duration. Approximately 15 to 25 per cent of exposed patients may experience a gradual decline in glomerular filtration rate. The outcome after lithium discontinuation varies.ObjectivesThis case study aims to analyze and document the clinical presentation, diagnosis, and management of lithium nephropathy in a patient with Bipolar Disorder.MethodsWe gathered data on the medical history, lab results, and treatment approach for a patient with Bipolar Disorder.ResultsThe patient, a 50-year-old woman, had been under the care of Psychiatry since 2008 due to a diagnosis of Bipolar Disorder Type I. During this time, she had experienced depressive and manic episodes but had not presented significant symptom decompensation for the past 14 years, successfully managed with lithium at a current dose of 600 mg per day. However, on this occasion, the patient sought hospitalization due to recent behavioural disturbances, including restlessness, disinhibition, abrupt changes in behaviour, pressured speech, sleep problems, agitation, and aggression. The patient also reported an increased sense of polyuria and polydipsia. Evaluation in the emergency department revealed elevated lithium levels of 1.47 mmol/L and hypokalemia, that justified lithium withdrawal. After lithium levels decreased, an estimated glomerular filtration rate remained low. She was diagnosed with lithium nephropathy, an adverse effect of long-term lithium therapy. Treatment with lithium changed to sodium valproate. Treatment with asenapine started and sustained for two months. Over the following two years, the patient experienced four additional hospital admissions in Psychiatry due to manic episodes.Conclusions Long-term lithium therapy can lead to lithium nephropathy with symptoms such as polyuria, polydipsia, and acute kidney failure. Consistent monitoring of patients receiving lithium is crucial to detect potential adverse effects.This case highlights the challenges in managing bipolar patients, as discontinuing lithium exacerbated symptoms despite switching to sodium valproate for nephropathy prevention. Long-term lithium treatment, while effective for bipolar disorder, poses significant renal risks. We emphasize continuous renal function monitoring and assessing the risk-benefit of lithium treatment while actively researching lithium nephropathy and its impact on glomerular function.Disclosure of InterestNone Declared

Surgical strategy in lithium-associated hyperparathyroidism: A population-based study.

The extent of parathyroidectomy (PTX) recommendation in patients with lithium-associated hyperparathyroidism (LAH) remains controversial. The primary objectives of this study were to analyze extent of surgery, complications, and long-term outcomes. A population-based study, including all primary hyperparathyroidism (PHPT) patients who underwent PTX in Sweden between 2008 and 2017. Data on exhibited lithium prescriptions, morbidity, surgical approach, and outcomes were collected from relevant national registers and the Scandinavian Quality Register of Thyroid, Parathyroid, and Adrenal Surgery. Patients with lithium exposure before PTX were defined as having LAH. Descriptive summary statistics and regression models were used to evaluate differences in comorbidities, surgical approach, and outcomes between LAH and PHPT not exposed to lithium (non-LAH). Lithium exposure was significantly more common among PHPT (n=202, 2.3%) than in controls (n=416, 0.5%); OR 5.0 (95% CI 4.2-5.9). The risk of LAH correlated to the length of lithium exposure. In the LAH-group, the surgical procedures were more extensive and associated with a higher risk of postoperative bleeding, wound infections, persistent hypercalcemia, and hypocalcemia that remained after adjustment for the higher percentage of multiglandular disease. However, the cumulative risk of re-admission for PHPT was similar the first years after PTX and primarily elevated for patients with >5years duration of lithium exposure prior to surgery. The findings support the perception of LAH as a complex entity. We recommend a functionally oriented approach, aimed to obtain and maintain normocalcemia for as long as possible, minimizing the risk of permanent hypoparathyroidism, and accepting some risk of recurrence.

Lifetime risk of severe kidney disease in lithium-treated patients: a retrospective study

BackgroundLithium is an essential psychopharmaceutical, yet side effects and concerns about severe renal function impairment limit its usage.AimsOur objectives were to quantify the occurrence of chronic kidney disease stage 4 or higher (CKD4 +) within a lithium-treated population, using age- and time-specific cumulative incidence and age-specific lifetime risk as measures of disease occurrence. Additionally, we aimed to investigate the association between the duration of lithium treatment and the risk of CKD4 + .MethodsWe identified patients from the Sahlgrenska University Hospital’s laboratory database. We conducted a retrospective cohort study employing cumulative incidence functions that account for competing deaths to estimate cumulative and lifetime risk of CKD4 + . A subdistribution hazards model was employed to explore baseline covariates. For measuring the association between the duration of lithium treatment and CKD4 + occurrence, we used a matched 1:4 case–control study design and logistic regression.ResultsConsidering a 90-year lifetime horizon, the lifetime risk of CKD4 + for patients initiating lithium treatment between ages 55 and 74 ranged from 13.9% to 18.6%. In contrast, the oldest patient group, those starting lithium at 75 years or older, had a lower lifetime risk of 5.4%. The 10-year cumulative risk for patients starting lithium between ages 18 and 54 was minimal, ranging from 0% to 0.7%. Pre-treatment creatinine level was a predictive factor, with a hazard ratio of 4.6 (95% CI 2.75–7.68) for values within the upper third of the reference range compared to the lower third. Moreover, twenty or more years of lithium exposure showed a strong association with an increased risk of CKD4 + compared to 1–5 years of lithium use, with an odds ratio of 6.14 (95% CI 2.65–14.26).ConclusionsThe risk of CKD4 + among lithium-treated patients exhibited significant age-related differences. Patients under 55 years old had negligible 10-year risk, while the lifetime risk for those aged 75 and older was limited. Duration of lithium treatment, especially exceeding 20 years, emerged as a significant risk factor. For individual risk assessment and prediction, consideration of age, pre-treatment creatinine levels, and the chosen time horizon for prediction is essential.

High lithium concentration at delivery is a potential risk factor for adverse outcomes in breastfed infants: a retrospective cohort study

BackgroundNeonatal effects of late intrauterine and early postpartum exposure to lithium through mother’s own milk are scarcely studied. It is unclear whether described symptoms in breastfed neonates are caused by placental lithium transfer or postnatal exposure to lithium through breastfeeding. We aimed to investigate lithium clearance and neonatal morbidity in breastfed infants with high versus low serum lithium concentrations at birth.MethodsThis retrospective study focused on breastfed infants to women treated with lithium during and after pregnancy, born between 2006 and 2021 in Stockholm, Sweden. Information on serum lithium concentrations and adverse neonatal outcomes was obtained from medical records. Neonatal symptoms and lithium clearance were compared between a high exposure group (HEG, lithium concentrations ≥ 0.6 meq/l) and a low exposure group (LEG, < 0.6 meq/l).ResultsA total of 25 infant-mother dyads were included. Median lithium serum concentration at birth was 0.90 meq/l in the HEG as compared with 0.40 meq/l in the LEG (p < 0.05). The difference was still significant at follow-up (0.20 meq/l vs 0.06 meq/l, p < 0.05), despite reduction in maternal dose. The rate of neonatal symptoms was 85.7% in HEG and 41.2% in LEG (p = 0.08) at birth and 28.6% vs 11.8% at follow-up (p = 0.55). Furthermore, 28.6% of infants in HEG were admitted to neonatal care, vs 5.9% in LEG (p = 0.19). Two infants in the HEG had therapeutic lithium levels at follow-up. All infants with symptoms at follow-up were either in the HEG or exposed to additional psychotropic medication.ConclusionsNeonatal symptoms are common after late intrauterine lithium exposure, however transient, treatable and mostly mild. In this study, a high lithium concentration at birth was a risk factor for an increased lithium level at follow-up. Polypharmacy may constitute an additional risk factor. This study suggests that the late intrauterine exposure to lithium might add to the adverse effects in lithium-exposed, breastfed infants. Consequently we recommend breastfed infants with therapeutic lithium concentrations at birth to be followed up promptly to avoid lithium toxicity.

Oxidative Stress Caused by Lithium Exposure in the Carassius auratus (goldfish) Liver Tissue

Lithium is a therapeutic agent widely used in the treatment of some psychiatric disorders. The aim of this study was to investigate the effects lithium-induced oxidative stress in liver tissue. In this study, Carassius auratus fish was used as a model organism and total 20 control fish and 28 experimental fishes were divided 4 subgroups randomly. Lithium chloride at a concentration of 50 mg/L was added to the glass tank of the experimental group. Fish were placed in two separate glass tanks, 20 in the control group and 28 in the experimental group. Lithium chloride at a concentration of 50 mg/L was added to the glass tank, which is the experimental group. At the 24th, 48th, 72nd and 96th hours of the study, 5 samples from the control group and 7 samples from the experimental group were included in the study in four different time periods. At the end of the study, it was determined that the level of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and acetylcholinesterase(AchE) decreased in the group with lithium exposure, while the levels of Malondialdehyde (MDA) increased. It was determined that oxidative stress occurred in lithium exposure.

Placental passage of lithium and neonatal complications after lithium exposure

Placental passage of lithium and neonatal complications after lithium exposure

Analysis of Impedance Spectra of a Lithium Electrode by the Distribution of Relaxation Times

The possibility of analyzing the electrochemical impedance spectra of lithium–lithium cells using the Distribution of Relaxation Times (DRT) function is studied. A comparative analysis of the electrochemical impedance spectra of lithium–lithium cells obtained during long-term storage at a constant temperature and at different temperatures was performed using the method of either equivalent electrical circuits or the DRT function. The analysis of the impedance of lithium–lithium cells by the DRT function is shown to allow estimating the number of layers in the surface film on the lithium electrodes and evaluating their physical parameters—the resistance and capacitance. It has been established that with a long exposure of lithium–lithium cells at the temperature of 30°C, the number of layers in the surface film and its resistance decreased. With the increase in the temperature, the physical properties of the layers of the surface film are differentiated and its total resistance decreased. The analysis of the electrochemical impedance spectra of lithium–lithium cells by the DRT functions is more informative than the method of equivalent electrical circuits.

Hesperidin via maintenance of mitochondrial function and antioxidant activity protects lithium toxicity in rat heart isolated mitochondria

Lithium is commonly used in the treatment of bipolar disorders (BD) and consumer electronics. It has been reported that lithium exposure is associated with mitochondrial dysfunction and oxidative stress in isolated cardiac mitochondria. Mitochondrial protection has a key role in myocardial tissue homeostasis, cardiomyocyte survival and inhibition of cardiotoxicity. Hesperidin as a flavanone and cardioprotective agent has shown high potential in antioxidant activity and restoration of mitochondrial dysfunction in different models. Therefore, we aimed to evaluate the ameliorative effects of hesperidin against lithium-induced mitochondrial toxicity in rat cardiac mitochondria. Isolated mitochondria were classified into six groups; control, lithium carbonate (125 µM), three groups of lithium + hesperidin-treated received lithium (125 µM) and hesperidin with various concentrations (10, 50, and 100 µM) and hesperidin (100 µM). Succinate dehydrogenases (SDH) activity, mitochondrial swelling, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), mitochondrial glutathione (GSH) and lipid peroxidation (LPO) were measured. The mitochondria received lithium showed a significant reduction of SDH activity, MMP collapse, mitochondrial swelling, induction of ROS formation and lipid peroxidation. However, we observed that the administration of hesperidin (50 and 100 µM) resulted in the increase of SDH activity, improved MMP collapse, mitochondrial swelling, and reduced ROS formation and lipid peroxidation. Also, there were no obvious changes in cardiac mitochondria received of hesperidin. These findings suggest that hesperidin could reduce lithium-induced mitochondrial dysfunction through antioxidant activities in cardiac mitochondria, may be beneficial for prevention and treatment of lithium toxicities, either as a drug to treat BD or as an environmental pollutant.

Focal adhesion is associated with lithium response in bipolar disorder: evidence from a network-based multi-omics analysis

Lithium (Li) is one of the most effective drugs for treating bipolar disorder (BD), however, there is presently no way to predict response to guide treatment. The aim of this study is to identify functional genes and pathways that distinguish BD Li responders (LR) from BD Li non-responders (NR). An initial Pharmacogenomics of Bipolar Disorder study (PGBD) GWAS of lithium response did not provide any significant results. As a result, we then employed network-based integrative analysis of transcriptomic and genomic data. In transcriptomic study of iPSC-derived neurons, 41 significantly differentially expressed (DE) genes were identified in LR vs NR regardless of lithium exposure. In the PGBD, post-GWAS gene prioritization using the GWA-boosting (GWAB) approach identified 1119 candidate genes. Following DE-derived network propagation, there was a highly significant overlap of genes between the top 500- and top 2000-proximal gene networks and the GWAB gene list (Phypergeometric = 1.28E–09 and 4.10E–18, respectively). Functional enrichment analyses of the top 500 proximal network genes identified focal adhesion and the extracellular matrix (ECM) as the most significant functions. Our findings suggest that the difference between LR and NR was a much greater effect than that of lithium. The direct impact of dysregulation of focal adhesion on axon guidance and neuronal circuits could underpin mechanisms of response to lithium, as well as underlying BD. It also highlights the power of integrative multi-omics analysis of transcriptomic and genomic profiling to gain molecular insights into lithium response in BD.

Does lithium poisoning induce brain injuries?-A histopathological rat study.

Due to a narrow therapeutic index, prolonged lithium treatment and overdose may result in neurotoxicity. Neurotoxicity is deemed reversible with lithium clearance. However, echoing the report of syndrome of irreversible lithium-effectuated neurotoxicity (SILENT) in rare severe poisonings, lithium-induced histopathological brain injuries including extensive neuronal vacuolization, spongiosis and ageing-like neurodegenerative changes were described in the rat following acute toxic and pharmacological exposure. We aimed to investigate the histopathological consequences of lithium exposure in rat models mimicking prolonged treatment and all three patterns of acute, acute-on-chronic and chronic poisonings observed in humans. We performed histopathology and immunostaining-based analyses using optic microscopy of brains obtained from male Sprague-Dawley rats randomly assigned to lithium or saline (controls) and treated according to the therapeutic or to the three poisoning models. No lesion was observed in any brain structure in any of the models. Neuron and astrocyte counts did not differ significantly between lithium-treated rats and controls. Our findings support that lithium-induced neurotoxicity is reversible and brain injury not a common feature of toxicity.

Removal of lithium from aqueous solutions by solid-phase extraction using sawdust loaded with magnetite nanoparticles and study of apoptosis, MDA and 8-OHdG caused by lithium toxicity in fish brain.

Lithium, which has a high industrial value, is an environmental pollutant of concern to those who work with lithium in industry as well as to the general public. Biological parameters such as MDA, 8-OHdG, apoptosis (caspase-3), and acetylcholinesterase (AChE) were studied to determine the toxic effects on the brain tissue of the model organism (Carassius auratus) exposed to high dose lithium. According to the results obtained, it was found that lithium exposure caused oxidative stress with an increase in MDA level over time and, accordingly, DNA damage and apoptosis occured in brain tissue. It was also found that a decrease in AChE activity was observed, and the high levels of MDA, 8-OHdG, and caspase-3 activity obtained in brain tissue supported this result. The solid phase extraction (SPE) method was used to effectively remove lithium, which has unfavorable effects on living organisms, from aqueous solutions. In this method, a sawdust loaded with magnetite nanoparticles (MNLS) was prepared as an adsorbent for solid phase extraction by a simple method, and it was characterized. Optimal conditions for the SPE process were defined and it was found that lithium could be removed from solution onto the MNLS surface with a high yield of about 96%. The results of the study are crucial for proposing a simple and applicable high performance method.

The effects of lithium on human red blood cells studied using optical spectroscopy and laser trap.

Lithium has been the treatment of choice for patients with bipolar disorder. However, lithium overdose happens more frequently since it has a very narrow therapeutic range in blood, necessitating investigation of its adverse effects on blood cells. The possible changes that lithium exposure may have on functional and morphological characteristics of human red blood cells (RBCs) have been studied ex vivo using single-cell Raman spectroscopy, optical trapping, and membrane fluorescent probe. The Raman spectroscopy was performed with excitation at 532nm light, which also results in simultaneous photoreduction of intracellular hemoglobin (Hb). The level of photoreduction of lithium-exposed RBCs was observed to decline with lithium concentration, indicating irreversible oxygenation of intracellular Hb from lithium exposure. The lithium exposure may also have an effect on RBC membrane, which was investigated via optical stretching in a laser trap and the results suggest lower membrane fluidity for the lithium-exposed RBCs. The membrane fluidity of RBCs was further studied using the Prodan generalized polarization method and the results verify the reduction of membrane fluidity upon lithium exposure.