Toxic Effects Of Lithium Research Articles

New insight into the toxic effects of lithium in the ragworm Perinereis cultrifera as revealed by lipidomic biomarkers, redox status, and histopathological features.

Lithium (Li) is a toxic monovalent alkaline metal used in household items common to industrial applications. The present work was aimed at investigating the potential toxic effects of LiCl on the redox status, fatty acid composition, and histological aspects of the marine ragworm Perinereis cultrifera. Sea worms were exposed to LiCl graded doses (20, 40, and 80mg/L) for 48h. Compared with the control group, the saturated fatty acids (SFA) decreased while monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA) increased upon exposure to LiCl. The increase in PUFA n-3 and PUFA n-6 was concomitant to an increase in docosahexaenoic (DHA: C22:6n-3), eicosapentaenoic (EPA: C20:5n-3), and docosapentaenoic acid (C22:5n-6) fatty acids. Results showed that LiCl-treated specimens accumulate lithium with increasing exposure gradient. Indeed, the exposure to LiCl doses promoted oxidative stress with an increase of the ferric reducing antioxidant power (FRAP), malondialdehyde (MDA), hydrogen peroxide (H2O2), advanced oxidation protein product (AOPP), and protein carbonyl (PCO) as well as the enzymatic and non-enzymatic antioxidants (non-protein thiols (NPSH), catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione S-transferase (GST), and metallothionein (MT)) levels in all treated groups. Our biochemical findings have been affirmed by the histopathological observations showing hyperplasia and loss of the intestine structure in treated specimens. Overall, our findings give new insights on the toxic effect of LiCl on the redox status of P. cultrifera body tissue and highlighted the usefulness of the FA composition as an early sensitive bioindicators to better understand LiCl mechanism of toxicity in marine polychaetes.

Estimation of acute toxicity of a drug based on the complex of lithium citrate, polymethylsiloxane, aluminum oxide

Research Institute of Clinical and Experimental Lymphology has developed an innovative drug based on a complex of lithium citrate, polymethylsiloxane and aluminum oxide (LOAP). Lithium-based drugs are effective in treating bipolar disorders. However, the toxic effects of lithium cause a “narrow therapeutic window”, which limits its clinical use. The creation of the drug LOAP was aimed at creating a prolonged form with a slow release of lithium to reduce toxic properties and use lithium citrate as an active pharmacological agent. At the moment, the lithium complex has no analogues. The purpose of the study was to study the parameters of acute toxicity of the LOAP. Material and methods. When studying acute toxicity, drugs were administered once intragastrically to mice and rats at doses of 12000, 10000, and 5000 mg/kg. Results. A single administration of drugs intragastrically through a probe in the maximum possible doses to mice and rats did not cause the death of animals and did not cause a locally irritating effect on the gastric mucosa. LOAP can be assigned to hazard class 4 (GOST 12.1.007-76).

Lithium in Environment and Potential Targets to Reduce Lithium Toxicity in Plants

Industrialization and inevitable mining have resulted in the release of some metals in environment, which have different uses on the one hand and also showed environmental toxicity. Lithium (Li) is one of them; however, its excess use in different fields or inappropriate disposal methods resulted in high Li accumulation in soil and groundwater. This subsequently is affecting our environment and more potentially our arable crop production system. In humans, Li has been extensively studied and causes numerous detrimental effects at different organ levels. Moreover, increases in Li in groundwater and food items, cases for mental disorders have been reported in different regions of the world. In plants, only a few studies have been reported about toxic effects of lithium in plants. Moreover, plant products (fruits, grains or other plant parts) could be a major source of Li toxicity in our food chain. Therefore, it is more imperative to understand how plants can be developed more tolerant to Li toxicity. In this short mini-review article, we primarily highlighted and speculated Li uptake, translocation and Li storage mechanism in plants. This article provides considerable information for breeders or environmentalist in identifying and developing Li hyperaccumulators plants and environment management.

Lithium Toxicity in an Elderly Women within Normal Therapeutic Range : A Case Report

Toxic effects of lithium are usually related to high serum levels. However, several cases of significant toxicity have occurred in patients whose serum levels fell within the normal therapeutic range. Such cases are rare, but individual variations may occur and clinical judgment rather than serum levels must determine the management. A 67 years old female with bipolar disorder on lithium was admitted with an acute confusional state, tremor, restlessness, increased nausea, slurred speech, polyuria and diarrhoea. Lithium level found to be 0.6 mmol/L that is in normal range. Neurotoxicity could be suspected at serum lithium levels which are considered therapeutic in young adults.Chatt Maa Shi Hosp Med Coll J; Vol.14 (2); Jul 2015; Page 78-79

Acute effects of lithium on excitability of human motor cortex

ObjectiveLithium has been widely used to treat bipolar affective disorder for over 60years. Still, its acute effects in human cerebral cortex are poorly understood. This study aimed at investigating the acute effects of lithium on motor cortex excitability as measured by transcranial magnetic stimulation (TMS). MethodsTen healthy young adults participated in a double-blind placebo-controlled randomized crossover study with four sessions, where a single oral dose of lithium carbonate (450mg, 900mg, or 1350mg) or placebo was tested. Focal TMS of the hand area of left motor cortex was used to test resting and active motor thresholds, motor evoked potential input–output curve (MEP IO-curve), slope of the MEP IO-curve and paired-pulse measures of intracortical inhibition and facilitation before, and two and four hours after drug administration. ResultsTwo hours post drug administration, 450mg of lithium carbonate increased the slope of the MEP IO-curve while 1350mg tended to decrease it. Lithium had no effect on motor thresholds, or intracortical inhibition or facilitation. ConclusionsThe acute effects of lithium on MEP IO-curve, a marker of corticospinal excitability, are consistent with an inverted U-shaped dose–response relationship. SignificanceFindings are important for our understanding of the therapeutic and toxic effects of lithium on the human central nervous system.

Lithium Use for Bipolar Disorder Post Renal Transplant

Lithium Use for Bipolar Disorder Post Renal Transplant

PIK3CA mutations and EGFR overexpression predict for lithium sensitivity in human breast epithelial cells

A high frequency of somatic mutations has been found in breast cancers within the gene encoding the catalytic p110α subunit of PI3K, PIK3CA. Using isogenic human breast epithelial cells, we have previously demonstrated that oncogenic PIK3CA "hotspot" mutations predict for response to the toxic effects of lithium. However, other somatic genetic alterations occur within this pathway in breast cancers, and it is possible that these changes may also predict for lithium sensitivity. We overexpressed the epidermal growth factor receptor (EGFR) into the non-tumorigenic human breast epithelial cell line MCF-10A, and compared these cells to isogenic cell lines previously created via somatic cell gene targeting to model Pten loss, PIK3CA mutations, and the invariant AKT1 mutation, E17K. EGFR overexpressing clones were capable of cellular proliferation in the absence of EGF and were sensitive to lithium similar to the results previously seen with cells harboring PIK3CA mutations. In contrast, AKT1 E17K cells and PTEN -/- cells displayed resistance or partial sensitivity to lithium, respectively. Western blot analysis demonstrated that lithium sensitivity correlated with significant decreases in both PI3K and MAPK signaling that were observed only in EGFR overexpressing and mutant PIK3CA cell lines. These studies demonstrate that EGFR overexpression and PIK3CA mutations are predictors of response to lithium, whereas Pten loss and AKT1 E17K mutations do not predict for lithium sensitivity. Our findings may have important implications for the use of these genetic lesions in breast cancer patients as predictive markers of response to emerging PI3K pathway inhibitors. See commentary: Treating PIK3CA and EGFR overexpressing breast cancers with lithium citrate

Lithium and inositol: effects on brain water homeostasis in the rat

Since its earliest use in psychiatry, lithium has been known to alter body water homeostasis. Although lithium is also known to decrease the concentration of inositol, an important brain osmolyte, little is known of the effects of lithium on brain water homeostasis. To determine whether lithium alters brain water homeostasis, and, if so, whether the mechanism involves changes in inositol concentration. Rats were fed regular food or regular food plus lithium chloride for either 11 days or 5 weeks. Brains were dissected and assayed for tissue water by the wet-dry method and for inositol by gas chromatography-mass spectrometry. We found a statistically significant (p=0.05, corrected) 3.1% mean elevation in frontal cortex tissue water in 5-week lithium-fed rats (86.7+/-3.9%), compared to control rats (83.6+/-2.6%). Inositol concentration correlated inversely with percent tissue water (r=-0.50, p=0.003, corrected) in pooled samples of 5-week lithium-fed rats, and was significantly lower in frontal cortex and hippocampus of 5-week lithium-fed rats, compared to controls. Rats fed lithium for 11 days did not differ significantly from controls on either variable. This is the first report of a lithium-induced increase in brain tissue water. Although the mechanism is unclear, it does not appear to result from changes in brain inositol concentration or blood sodium concentration. This finding may have implications for the therapeutic or toxic effects of lithium on brain, because increased tissue water can augment cell excitability.

In vitro effects of lithium and nickel at different levels on Neuro-2a mouse Neuroblastoma cells

Lithium and nickel present low toxicity, but are able to cause alterations in different tissues. The toxic effects of lithium and nickel at different cellular levels were assessed using two inorganic chemical species: lithium chloride and nickel(II) chloride. Mouse neuroblastoma cell cultures (Neuro-2a) were exposed to both compounds for 24 h. The cytotoxic effects evaluated were cell proliferation by quantification of total protein content, cytoplasmic membrane integrity to cytosolic lactate dehydrogenase leakage, and lysosomal hexosaminidase release. Metabolic markers were lactate dehydrogenase activity and mitochondrial succinate dehydrogenase activity. Lysosomal markers were relative neutral red uptake by lysosomes, and lysosomal hexosaminidase sphingolipid degradation activity. Acetylcholinesterase activity on intact cells was also quantified. Nickel was found to be 36 times more toxic than lithium to neuroblastoma cell proliferation (EC 50= 0.29 and 10.5 m m, respectively), but the relative extent of other alterations differed. Lithium stimulated nearly all the indicators studied, particularly lactate dehydrogenase, mitochondrial succinate dehydrogenase and acetylcholinesterase activities, as well as hexosaminidase release. In contrast, nickel mainly stimulated hexosaminidase release and inhibited lactate dehydrogenase activity. The stabilization of the cytoplasmic membrane to lactate dehydrogenase leakage simultaneously with the secretion of lysosomal hexosaminidase for both compounds also shows that functional metabolic alterations produced by lithium and nickel are more important than cytoplasmic damage.

Untoward Effects of Lithium Treatment in Children Aged Four through Six Years

To explore the relationship between lithium dose and serum lithium level on the occurrence of untoward or toxic effects of lithium in the treatment of 20 hospitalized aggressive and/or mood-disordered children aged 4 through 6 years. Clinical and research records of 20 children treated with lithium according to an established inpatient protocol were reviewed. Side effects as reported by psychiatric staff were categorized by organ system affected and severity. During the initial 2 weeks of lithium treatment, 60% of the children manifested one or more types of side effects, most commonly central nervous system effects. Side effects were seen at doses of 25.6 to 52.1 mg/kg per day and at serum levels from 0.65 to 1.37 mEq/L. In general, adverse effects were associated with higher lithium doses and lithium levels and were most common during the first week of treatment. A potential interaction between concurrent infection and more severe side effects was seen. Side effects occur frequently in children aged 6 years and younger during the initiation phase of lithium treatment; are related to higher milligram per kilogram doses, higher serum lithium levels, and phase of treatment; and may be related to concurrent medical illness.

Lithium for Zidovudine-Induced Neutropenia in AIDS-Reply

In Reply.— Drs Nathwani and Green are correct that the toxic effects of lithium are a real danger because of the polyinfections and frequent diarrhea of patients with acquired immunodeficiency syndrome (AIDS). We start with 300 mg of lithium carbonate twice daily, and only occasionally have to raise it to three times daily. We monitor serum lithium levels twice weekly for the first few weeks and reduce the dose if any serum lithium level reaches 1.40 mmol/L or if the patient reports a hand tremor or any other sign 1 of a toxic reaction to lithium. We strive for a serum level of 0.60 to 1.20 mmol/L (>1.50 mmol/L signals a toxic effect). 1 Our experience is that lithium does not exacerbate erythrocyte macrocytosis in AIDS. In that connection, we find negative balance for vitamin B 12 and folate to be frequent in AIDS, 2 often being indicators of generalized

Current determination of lithium-induced minimum sodium requirement in rats.

Lithium administration raises the minimum sodium requirement of the organism. Lithium treated-rats drink spontaneously a hypertonic sodium chloride solution and thereby protect themselves against the toxic effects of lithium. In the present paper it was studied whether the consumption of sodium chloride can be used as a quantitative measure of the sodium requirement. Rats given different amounts of lithium with food for about 2 months were given free access to water and a 0.46 M NaCl solution, and the 24-h intake of the latter was followed. It was found that the consumption of hypertonic sodium chloride increased with the lithium dosage and the serum lithium level. The consumption showed the following characteristics: (a) It was sufficient to prevent death from lithium poisoning. (b) When access to hypertonic chloride was discontinued for 48 h, the rats lost body weight; the body weight was reestablished within 1 h when the rats again had access to sodium chloride solution. (c) When sufficient amounts of sodium were given with the food, the lithium-treated rats drank no more sodium chloride solution than did the control rats. (d) When lithium administration was discontinued, the consumption of sodium chloride solution fell within 10 days to the control level. (e) The lithium-treated rats developed polyuria, but this was not the cause of the extra intake of sodium chloride. (f) The lithium-treated rats did not drink more of the hypertonic sodium chloride solution than was necessary to cover the minimum sodium requirement. The results indicate that the intake of hypertonic sodium chloride solution can, in fact, be used as a measure of the minimum sodium requirement in lithium-treated rats.

Toxic effects of lithium in newborn infants: A commentary

Toxic effects of lithium in newborn infants: A commentary

Studies on the Crayfish Plague Fungus Aphanomyces astaci

AbstractA mycelial suspension of the crayfish plague fungus, Aphanomyces astaci, was able to produce large numbers of zoospores, when transferred to redistilled water, at 20°C, even after storage for months at 2°C. Spore production was greater in redistilled water than in tap water and heavier under shake conditions than under stationary ones. In buffered redistilled water sporulation occurred between pH 5 and 8 and the optimal range was about pH 5 to 7.Of the tested aliphatic alcohols, aldehydes, and carboxylic acids, the long analogues were more toxic to spore formation than the shorter ones. Ethylenediamine‐tetraacetic acid (EDTA) prevented sporulation probably by removing some essential metal (s) with an affinity for EDTA near that of calcium. Calcium protected against the toxic effect of lithium, sodium, and potassium. Magnesium, only tested against lithium, had no such protecting effect.Cu2+, Ni2+, Zn2+, Co2+, K+ Mn2+, NH4+, Li+, Na+, Ca2+, Mg2+ was the approximate order among tested cations in their ability to stop the swimming stage of the zoospores, the first mentioned being the most effective ones. Nitrate and acetate were more active in the same respect than sulphate, chloride, phosphate, or bicarbonate. The optimal pH range for swimming seemed to be pH 6–7.5, and the maximal range 4.5–9.0.The zoospores showed no chemotactic response to tested substances. The germination ability was as high in horse blood as in crayfish blood. A spore suspension stored for 2 months at 2°C still contained viable spores.