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[Effect of lithium chloride on the thyroid gland of white rats].

The morphological and functional changes in the thyroid tissue of white rats injected lithium chloride at doses 0.5 mekv/kg and 1.0 mekv/kg (groups 1 and 2, respectively) during three weeks were studied by the radiometric, histological and biochemical methods. The radiometric, histological and biochemical methods. The inhibitory action of lithium chloride on hormonogenesis in the thyroid gland and secretion of thyroid hormones into the blood was proved to be directly related to the lithium dose and concentration in the blood. The data of intravital radiometric and morphological analysis of the organs of the 1st group animals suggest some activization of the gland function, with the secretion of the hormones into the blood being suppressed. Increased concentration of the drug inhibits hormonogenesis and secretion of thyroid hormones into the blood.

Animals↗

Comparison of larkspur alkaloid extract and lithium chloride in maintaining cattle aversion to larkspur in the field.

Lithium chloride (LiCl) and larkspur (Delphinium barbeyi) alkaloid extract were compared in their effect as an emetic to create taste aversions to fresh larkspur. They were further compared in the field to determine whether the indigenous larkspur alkaloids were more effective in maintaining the aversion when conditioned cattle were subjected to the social pressure (social facilitation) of control cattle eating larkspur. Taste aversions were produced in two groups of 1-yr-old cattle by offering fresh larkspur and then gavaging with either LiCl at 200 mg/kg of BW or larkspur alkaloid extract at 1.1 to 1.6 mL/kg of BW. The third group (control) was gavaged with water. The alkaloid group was slower to form an aversion than the lithium group, requiring four doses compared with two doses. All groups were then taken to larkspur-infested rangeland to test the aversion in the field. In the first field trial in which groups grazed separately, both aversion-induced groups generally abstained from eating larkspur. In the second trial in which all groups grazed together, both aversion-induced groups consumed less than half as much larkspur as the controls, but neither group abstained completely. Larkspur alkaloids did not maintain the aversion to larkspur to a greater degree than did LiCl when aversion-induced cattle were subjected to social facilitation.

Alkaloids↗

Neurosecretory and microstructural changes in the hypothalamus of rats following administration of lithium chloride and 3H-thymidin.

Adult male rats were intraperitoneally administered aqueous solution of lithium chloride (LiCl). Studies, including neurosecretory and microstructural changes within particular neurocytes in supraoptic (NSO) and paraventricular nuclei (NPV) were performed on hypothalamic sections. In the experimental rats the administered LiCl increased the level of GOMORI-positive neurosecretory material both in supraoptic and paraventricular nuclei. Great amounts of the neurosecretory material were markedly conspicuous in the above areas after 20 days of LiCl administration. Investigations carried out on cellular nuclei of particular neurocytes showed a significant enlargement of the nuclei, and statistical calculations revealed that, in comparison with the basic control, the difference was essentially significant (p less than 0.001). 3H-thymidin administration to the rats which had previously been on LiCl for 20 days demonstrated also that within supraoptic nuclei the incorporation of the isotope in cellular nuclei took a faster course than in control animals.

Animals↗

A comparison between effects of intraventricular insulin and intraperitoneal lithium chloride on three measures sensitive to emetic agents.

When low doses of insulin are infused directly into the third ventricle, rats reduce their food intake and lose weight. To determine whether these effects could be due to malaise induced by the treatment, the effects of intraventricular insulin were compared to the effects of the emetic agent lithium chloride to condition a taste aversion, to stimulate oxytocin secretion, and to reduce sodium appetite in response to furosemide treatment. For all three of these measures, lithium chloride treatment had a predictable effect compared to controls. Specifically, lithium caused a significant taste aversion, elevated plasma oxytocin, and attenuated sodium appetite. However, lithium did not produce a significant change in food intake or body weight. On the other hand, intraventricular insulin treatment did cause a significant reduction in body weight yet had no effect on these indices of malaise in the rat. These data are consistent with the hypothesis that intraventricular insulin does not reduce food intake and body weight by producing malaise but rather serves as a negative feedback signal of body adiposity to the central nervous system.

Animals↗

Copulation-illness associations in male rats: lithium chloride dose and delay manipulations.

Male rats that receive an injection of lithium chloride (LiCl) after each pairing with an estrous female gradually decrease their copulatory behaviors. In the present experiments we demonstrated that a 6.0 mEq/kg (0.3 M, 20 ml/kg) dose of LiCl injected after trials spaced twice weekly at 3-4-day intervals induced more rapid acquisition of copulation-illness associations than a 3.0 mEq/kg (0.15 M, 20 ml/kg) dose. Contingent 0.3 M saline or noncontingent 0.3 M LiCl injections did not affect copulatory behaviors. The location of the male rat (home cage or test chamber) during a portion of the aversive state induced by LiCl did not influence rate of acquisition. Copulation-illness associations, once established, were retained over a 60-day interval. Comparable decrements in copulatory behaviors were evident when LiCl was injected at 1-, 5-, or 15-min intervals after pairings with estrous females when the males were detained in the test chambers during the delay intervals; decrements were not observed when the interval was increased to 30 or 60 min. An electric shock analog to the aversive state induced by LiCl did not induce decrements in copulatory behaviors. It was suggested that odor-illness associations may, in part, account for the decrements in copulatory behaviors in this paradigm.

Animals↗

Intracellular ionized calcium and increasing doses of lithium chloride therapy in healthy Sprague-Dawley rats.

The use of lithium salts in the prophylaxis and treatment of several psychiatric and neurologic disorders continues to be well accepted despite the apparent lack of understanding regarding its mode of action at the molecular level. This lack of delineation in the mechanism of action is supported by numerous conflicting publications. Despite the lack of understanding, a role for calcium in the manifestation of lithium's action is a constant singular consensus. Intracellular ionized calcium ([Ca2++]i) is involved in the proper functioning of cells because of its role in the second messenger pathway. It is therefore essential to evaluate the effect of lithium on intracellular calcium metabolism in a well-defined system. In this study, platelets loaded with Fura-2-Acetoxymethyl were used to evaluate the effect of intraperitoneally administered lithium chloride at 0, 2.5, 5.0, 7.5, and 10 mmol/kg body wt. on [Ca++]i. The results showed a slight relative increase in serum Ca++ that correlated well with the dose of LiCl administered to the rats. The baseline [Ca++]i were comparable in the study groups, but the response to thrombin stimulation was more pronounced at LiCl doses of 2.5, 5.0, and 7.5/kg body wt. compared with control and rats treated with 10 mmol LiCl/kg body wt. This finding suggests a dose-dependent response of [Ca++]i to LiCl treatment. The observation may therefore explain the variations that have been reported in [Ca++]i studies with respect to LiCl therapy using different doses.

Animals↗

Effect of lithium chloride on ornithine decarboxylase activity in rat adrenal.

The effects of lithium chloride on ornithine decarboxylase (ODC) activity were compared in the adrenal and kidney of control (saline treated) and prolactin-treated rats. ODC activity was decreased in kidney of both groups of animals, the magnitude of the effect of lithium in the hormone-treated group varying with the time of administering the lithium relative to prolactin. The response in the adrenal was quite different. Following treatment with LiCl, there was a gradual increase in ODC activity from a low of 10-35 pmol CO2 x 30 min-1.mg protein-1 in control animals to values 20- to 30-fold greater at 5 h. In rats treated simultaneously with LiCl and prolactin, ODC activity was greater at 5 h than that observed in animals receiving either compound alone, indicating that their effects were additive. When LiCl was given 4 h after prolactin, i.e., 1 h before sacrifice, ODC activity decreased to a very low level at 5 h, as in other tissues. The increase in ODC activity in the adrenal following LiCl is of the same magnitude as the changes observed in tissues stimulated to undergo alterations in proliferation, differentiation, or metabolic or membrane activity by hormones and other external stimuli.

Adrenal Glands↗

Conditioned responses to a taste conditioned stimulus paired with lithium chloride administration.

The present experiments examined whether behavioral conditioned responses (CRs) develop to lithium chloride (LiCl)-paired tastes and whether these CRs are similar to the behaviors that follow administration of the drug. Rats were exposed to a saccharin solution via intraoral infusions before being injected with either LiCl or saline. CRs were assessed after conditioning when the saccharin conditioned stimulus was delivered alone. The unconditioned response to LiCl delivery is a very distinctive posture that has been termed "lying-on-belly." The present study indicates that this behavior pattern also occurs after the delivery of a LiCl-paired taste solution. The similarity between these unconditioned and conditioned behaviors is consistent with the hypothesis that responses are conditioned during taste aversion acquisition and that CRs are similar to those that are generated by the drugs used in conditioning.

Animals↗

Production of and response to interleukin-2 by cultured T cells: effects of lithium chloride and other putative modulators.

Immunomodulating substances may be useful as host-modifying adjuvants in patients receiving immunosuppressive therapies or as probes for studying the immune system. Detection of interleukin-2 (IL-2) is possible via a microassay, enabling investigation of the effects of immunomodulating agents on T cell production of and response to IL-2 in vitro. Four such agents were examined: lithium chloride, Bestatin, Azimexon, and muramyl dipeptide (MDP). All four agents increased the response of cultured T cells to IL-2 over control populations supplied with IL-2 alone. Lithium chloride, Bestatin, and MDP enhanced the production of IL-2 in standard mixed lymphocyte cultures over control cultures receiving media alone. These results suggest that several immunomodulators may produce their effects by the modulation of IL-2 or other lymphokines. Additionally, microassay systems may prove useful as probes to elucidate the function of putative immunoregulatory substances.

Acetylmuramyl-Alanyl-Isoglutamine↗

Conditioned taste reactivity in rats after phenylpropanolamine, d-amphetamine or lithium chloride.

That an aversive property of phenylpropanolamine (PPA) in part contributes to its anorexic capacity is suggested by the demonstration of conditioned taste avoidance to PPA doses ranging from 10-40 mg/kg. In order to further evaluate the putative aversive property of PPA, the present experiment compared the effects of PPA on multiple measures of aversion (chin rubs, gaping) in the taste reactivity (TRT) paradigm with those produced by the classic agent lithium chloride and by amphetamine. Male rats were infused via an intraoral cannula with 0.5 M sucrose followed by injection with either vehicle, 127 mg/kg lithium chloride (LiCl), 1.5 or 3.0 mg/kg amphetamine or by 10, 20 or 40 mg/kg PPA. LiCl and 40 mg/kg PPA induced significant chin rub responses during conditioning but only the aversive response induced by 40 mg/kg PPA persisted during extinction trials. In contrast, lower doses of PPA (10 mg/kg, 20 mg/kg) were not aversive in the TRT paradigm. These results suggest that an aversive component is not contributing to anorexia induced by PPA within the dose range of 10-20 mg/kg, but that higher doses may further suppress appetite via an aversive action.

Animals↗

[Effect of diuretics on lithium chloride toxicity].

Experiments on guinea-pigs, albino rats and mice have shown that administration of novurint, cyclomethiatiazid, hypothiazid, diacarb and lasix provides no favourable results in acute poisoning with LD50 and LD90 of lithium chloride. Euphylline is effective only after administration of LD50 of lithium chloride.

Animals↗

The effect of lithium chloride treatment on cell-mediated immunity in mice.

The immunomodulatory effect of lithium chloride (LiCl) administered i.p. to adult mice (150 mg/kg/day) on cellular immunity in vivo was investigated. A short (6-day) treatment with LiCl of either spleen cell donors in semiallogeneic or xenogeneic GVH reaction, or recipients in semiallogeneic HVG reaction, significantly diminished the early sings of local cell-mediated immunity. A short-term LiCl treatment of donor mice also abrogated systemic GVH reaction in newborn F1 recipients, while a treatment prolonged for 20 days did not alter the high GVH response of spleen cells typical for untreated donors. Thus, a striking time-dependent efficacy of LiCl on the reduction of GVH reaction was found.

Animals↗

In vitro interleukin-8 production by monocytes treated with lithium chloride from breast cancer patients.

AIMS AND BACKGROUND: Since interleukin-8 (IL-8) has a suppressive effect on hematopoiesis, lithium induces leukocytosis and granulocytosis and mononuclear cells are defective in patients affected by neoplastic disease, we analyzed IL-8 production by monocytes obtained from patients with nonmetastatic breast cancer (BCaM0) and metastatic breast cancer (BCaM1) and the effect of lithium chloride (LiCl) on these cells. Lithium salt compounds are used to limit the degree and duration of neutropenia in patients receiving chemotherapy for cancer and acute leukemia. Lithium influences the hematopoietic system, which is known to be regulated by numerous cytokines including IL-8. METHODS: We selected three groups of subjects (15 per group): patients affected by BCaM0, BCaM1 and healthy donors (HD) matched for sex and age. IL-8 release was assessed in supernatants of lipopolysaccharide (LPS) and/or LiCl-treated monocyte cultures. RESULTS: Monocytes from BCaM1 released higher IL-8 levels than monocytes from BCaM0 (P <0.0001); the IL-8 levels of both groups were significantly higher (P <0.0001) than those of HD. In vitro LiCl treatment reduced IL-8 production by monocytes obtained from all subjects compared to the same cells when untreated or LPS treated. The suppressive effect of LiCl on IL-8 production by monocytes from breast cancer patients was particularly marked in monocytes from BCaM0 with respect to those from BCaM1. LPS treatment increased the IL-8 production more in BCaM1 monocytes than in BCaM0 monocytes. Moreover, combined LPS/LiCl treatment of monocytes significantly (p <0.0001) downregulated the release of IL-8 compared to treatment with LPS alone. CONCLUSIONS: Our data demonstrate that monocytes from BCaM0 release larger amounts of IL-8 than monocytes from BCaM0 and from HD. Lithium was able to downregulate IL-8 production by monocytes from different subgroups. Further studies are needed to clarify if the improvement of the hematopoietic system in vivo observed following lithium therapy could reside, at least in part, in the ability of lithium to downregulate this chemokine.

Adjuvants, Immunologic↗

Strain dependent rate of Li+ elimination associated with toxic effects of lethal doses of lithium chloride in mice.

Strain differences in response to the administration of two lethal doses (700 and 900; mg/kg) of lithium chloride were studied in eight week old males from six genetic strains of mice. Two parameters were considered; (a) toxicity (time to death) and (b) hypothermia. Lithium distribution in the body (blood, seven tissues, excreta and urine) were evaluated for each strain following IP injection of 200 mg/kg dose of LiCl. The strain differences were significant for toxicity. The order of susceptibility of the strains was 129/ReJ greater than S.W. greater than C3H/S greater than DBA/2 = Balb/c greater than C57/6J with a 15-fold difference between the most susceptible and the least susceptible strain at the 900 mg/kg dose. Strain differences for hypothermic response at both doses were not significant. Significant strain differences were also observed for lithium distribution in different parts of the body, excreta and urine. The concentration of Li+ found in urine and excreta was positively correlated with resistance (time to death at 900 mg/kg LiCl) to the toxic effect of lithium. The lithium concentration in blood, muscle and lung on the other hand reflected a negative correlation with toxicity. The susceptibility of a strain could be characterized by its inherent lithium excretory ability, particularly through urine. It may suggest an involvement of membrane transport mechanisms in determining toxicity to lithium compounds.

Animals↗

Effect of lithium chloride on adrenocortical activity in male rats: evidence of dose and duration dependent response.

Changes in the adrenal weight, adrenal 5-ene-3 beta-hydroxysteroid dehydrogenase (5-ene-3 beta-HSD) activity and serum levels of corticosterone were observed in male wistar rats after the treatment of lithium chloride in the doses of 100, 200 and 400 micrograms/100 g of body weight/day for 7, 14 and 21 days. The experiments indicate that 200 and 400 micrograms/100 g.b.w. administered for 14 and 21 days caused a significant stimulation in the activities of adrenal 5-ene-3 beta-HSD along with elevation of adrenal weights and serum levels of corticosterone. 100 micrograms of lithium chloride was not able to modulate the adrenal activity. Moreover, plasma levels of lithium remain in therapeutic range in this experiment at the doses of 200 and 400 micrograms/100 g body weight. Therefore, our data suggest that lithium can alter the adrenal activity within its therapeutic range according to the duration of treatment.

3-Hydroxysteroid Dehydrogenases↗

Effects of intraperitoneal injection of lithium chloride on neurohypophyseal activity: implications for behavioral studies.

Intraperitoneal injections of lithium chloride (LiCl) were found to increase the activity of vasopressin-neurons and oxytocin-neurons as indexed by rises in plasma concentrations of vasopressin-associated neurophysin (VP-RNP) and oxytocin-associated neurophysin (OT-RNP). Plasma VP-RNP increased 12 and 4 times basal levels (greater than or equal to 20 fmol/ml) reaching values of 248 +/- 37 fmol/ml (3.0 mEq LiCl/kg body weight) and 89 +/- 10 fmol/ml (1.5 mEq LiCl/kg body weight) at 60 minutes. OT-RNP rose to 37-and 10-times basal levels (greater than or equal to 20 fmol/ml) with peak values of 749 +/- 100 fmol/ml and 188 +/- 48 fmol/ml ten minutes following injection of 3.0 or 1.5 mEq LiCl/kg body weight. Mean arterial pressure increased in response to lithium treatment by 31 +/- 6 mm Hg at 60 minutes in rats receiving 3.0 mEq LiCl/kg and by 22.5 +/- 5 mm Hg at 10 minutes in rats receiving 1.5 mEq LiCl/kg over pretreatment values (125 +/- 3 mm Hg). Heart rate decreased from a pretreatment value of 422 +/- 12 beats/min to 367 +/- 48 beats/min at 10 minutes and to 341 +/- 27 beats/min at 20 minutes for rats treated with the high and low dose of lithium, respectively. These findings suggest that the behavioral effects of LiCl could result from multiple mechanisms and involve its acute release of vasopressin and oxytocin. It is also possible that changes in cardiovascular function may act as cues when LiCl is used as an aversive stimulus.

Animals↗

[Effect of lithium chloride on bioelectric activity of the cortex and various subcortical structures of rabbit brain].

In a dose of 100 mg/kg and with intravenous administration to rabbits lithium chloride produces a depressing influence on the spontaneous bioelectric activity of the cerebral cortex and its subcortical formations, which extends from the cortex to subcortical structures. The compound brings down the electric excitability of the hippocampus, caudate nucleus, tonsils, reticular formation of the mesensephalic segment and of the thalamus, while in a dose of 300 mg/kg it increases the excitability of the motor cortex. No correlation between the lithium chloride induced electroencephalographic changes in the cerebral structures, on the one hand, and the content therein of biogenic amines and accumulation of lithium ions, on the other, was revealed.

Action Potentials↗

Isolating RNA from clinical samples with Catrimox-14 and lithium chloride.

RNA is a highly informative molecule that has great potential as a target for diagnostic studies. This potential can be reached only when reliable methods for isolating RNA are available in the clinical environment. Cationic surfactants lyse cells and precipitate nucleic acids. We have described a novel cationic surfactant (tetradecyltrimethylammonium oxalate, Catrimox-14), which is particularly effective in precipitating RNA from cells and which can be applied to clinical specimens. We examine the utility of a method of recovering RNA from the surfactant-nucleic acid precipitate, in which 2 M lithium chloride is used to extract the DNA and surfactant from the precipitate; RNA (being insoluble in lithium chloride solution) remains in the pellet. The yield of RNA from peripheral blood mononuclear cells by the Catrimox-LiCl method we describe was the same yield by a conventional method using guanidine thiocyanate, phenol, and chloroform (GPC). The quality of the RNA, judged by agarose gel electrophoresis, A260/280 ratio and its ability to serve as a target for reverse transcription and PCR, was the same. RNA was isolated and amplified from blood stored for at least 2 weeks in Catrimox solution at room temperature. RNA was also easily isolated with the Catrimox-LiCl method in good yield from frozen sections of mouse liver, spleen, kidney and brain, and from core biopsies of liver and kidney. RNA isolated from needle aspirates of liver, spleen, kidney, pancreas, and brain was easily amplified by RT-PCR. The Catrimox-LiCl method is simple and does not call for the use of corrosive reagents. The Catrimox-LiCl method removes 98% of the DNA. We conclude that the Catrimox-LiCl method is suitable for use in clinical applications of RNA-based diagnosis.

Animals↗