Lithium Therapy Effects on the Reproductive System

Filippa, Verónica; Mohamed, Fabián

doi:10.1007/978-3-319-95360-1_16

Cited by 6 publications

(8 citation statements)

References 120 publications

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“…Despite its tremendous clinical value, several adverse effects have been attributed to Li + ( 1 ). Several reports of Li + -induced reproductive toxicity have also been reported ( 2 , 16 , 20 , 26 ). Unfortunately, there is no precise mechanism(s) for Li + -induced reproductive toxicity.…”

Section: Discussionmentioning

confidence: 96%

“…Several investigations mentioned the primary role of oxidative stress (OS) in the pathogenesis of reproductive system dysfunction ( 16 , 20 , 26 , 101 ). Many anomalies in the functionality of spermatozoa are attributed to the increased level of ROS in testis and semen ( 37 – 40 ) through severe impairments of DNA, interruption of plasma membrane integrity, and denaturation of proteins ( 41 – 43 ).…”

Section: Discussionmentioning

confidence: 99%

“…Li + is a drug with adverse effects on the reproductive system. There are several lines of evidence indicating the pivotal role of OS in the pathogenesis of Li + -induced reproductive toxicity ( 2 , 16 , 20 , 26 ). At the sub-cellular levels, we found that sperm mitochondria are a critical target for Li + -induced sperm abnormalities.…”

Section: Discussionmentioning

confidence: 99%

“…The role of OS in the mechanism of metals-induced cytotoxicity has been widely investigated ( 34 – 36 ). There are several lines of evidence mentioning the role of OS in the pathogenesis of Li + -induced adverse effects in the testis tissue and semen in both experimental models and human cases ( 19 , 20 ). For instance, many anomalies in the functionality of spermatozoa are attributed to the increased level of ROS in testis and semen ( 37 – 40 ) through severe impairments of DNA, interruption of plasma membrane integrity, and denaturation of proteins ( 41 – 43 ).…”

Section: Introductionmentioning

confidence: 99%

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The Role of Mitochondrial Impairment and Oxidative Stress in the Pathogenesis of Lithium-Induced Reproductive Toxicity in Male Mice

et al. 2021

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Lithium (Li+) is prescribed against a wide range of neurological disorders. Besides its excellent therapeutic properties, there are several adverse effects associated with Li+. The impact of Li+ on renal function and diabetes insipidus is the most common adverse effect of this drug. On the other hand, infertility and decreased libido is another complication associated with Li+. It has been found that sperm indices of functionality, as well as libido, is significantly reduced in Li+-treated men. These adverse effects might lead to drug incompliance and the cessation of drug therapy. Hence, the main aims of the current study were to illustrate the mechanisms of adverse effects of Li+ on the testis tissue, spermatogenesis process, and hormonal changes in two experimental models. In the in vitro experiments, Leydig cells (LCs) were isolated from healthy mice, cultured, and exposed to increasing concentrations of Li+ (0, 10, 50, and 100 ppm). In the in vivo section of the current study, mice were treated with Li+ (0, 10, 50, and 100 ppm, in drinking water) for five consecutive weeks. Testis and sperm samples were collected and assessed. A significant sign of cytotoxicity (LDH release and MTT assay), along with disrupted testosterone biosynthesis, impaired mitochondrial indices (ATP level and mitochondrial depolarization), and increased biomarkers of oxidative stress were detected in LCs exposed to Li+. On the other hand, a significant increase in serum and testis Li+ levels were detected in drug-treated mice. Moreover, ROS formation, LPO, protein carbonylation, and increased oxidized glutathione (GSSG) were detected in both testis tissue and sperm specimens of Li+-treated mice. Several sperm anomalies were also detected in Li+-treated animals. On the other hand, sperm mitochondrial indices (mitochondrial dehydrogenases activity and ATP levels) were significantly decreased in drug-treated groups where mitochondrial depolarization was increased dose-dependently. Altogether, these data mention oxidative stress and mitochondrial impairment as pivotal mechanisms involved in Li+-induced reproductive toxicity. Therefore, based on our previous publications in this area, therapeutic options, including compounds with high antioxidant properties that target these points might find a clinical value in ameliorating Li+-induced adverse effects on the male reproductive system.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The Role of Mitochondrial Impairment and Oxidative Stress in the Pathogenesis of Lithium-Induced Reproductive Toxicity in Male Mice

et al. 2021

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“…Besides, Li + can regulate synaptic plasticity by suppressing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor trafficking [ 54 ]. Despite its therapeutic effects on neurological and psychiatric disorders, it can disturb the neuroendocrine axis, mainly in hypothalamic-pituitary-thyroid, hypothalamic-pituitary-gonadal, and hypothalamic-pituitary-adrenal axis in patients under lithium therapy [ 55 , 56 ]. Besides, oral lithium administration can result in Li + accumulation in central neuroendocrine tissues, such as the hypothalamus and pituitary gland [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

Lithium Enhances the GABAergic Synaptic Activities on the Hypothalamic Preoptic Area (hPOA) Neurons

Rijal

Jang

Park

et al. 2021

IJMS

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Lithium (Li+) salt is widely used as a therapeutic agent for treating neurological and psychiatric disorders. Despite its therapeutic effects on neurological and psychiatric disorders, it can also disturb the neuroendocrine axis in patients under lithium therapy. The hypothalamic area contains GABAergic and glutamatergic neurons and their receptors, which regulate various hypothalamic functions such as the release of neurohormones, control circadian activities. At the neuronal level, several neurotransmitter systems are modulated by lithium exposure. However, the effect of Li+ on hypothalamic neuron excitability and the precise action mechanism involved in such an effect have not been fully understood yet. Therefore, Li+ action on hypothalamic neurons was investigated using a whole-cell patch-clamp technique. In hypothalamic neurons, Li+ increased the GABAergic synaptic activities via action potential independent presynaptic mechanisms. Next, concentration-dependent replacement of Na+ by Li+ in artificial cerebrospinal fluid increased frequencies of GABAergic miniature inhibitory postsynaptic currents without altering their amplitudes. Li+ perfusion induced inward currents in the majority of hypothalamic neurons independent of amino-acids receptor activation. These results suggests that Li+ treatment can directly affect the hypothalamic region of the brain and regulate the release of various neurohormones involved in synchronizing the neuroendocrine axis.

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Taurine mitigates the development of pulmonary inflammation, oxidative stress, and histopathological alterations in a rat model of bile duct ligation

Ommati

Mobasheri

et al. 2022

Naunyn-Schmiedeberg's Arch Pharmacol

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Lung injury is a significant complication associated with cholestasis/cirrhosis. This problem significantly increases the risk of cirrhosis-related morbidity and mortality. Hence, finding effective therapeutic options in this field has significant clinical value. Severe inflammation and oxidative stress are involved in the mechanism of cirrhosis-induced lung injury. Taurine (TAU) is an abundant amino acid with substantial anti-inflammatory and antioxidative properties. The current study was designed to evaluate the role of TAU in cholestasis-related lung injury. For this purpose, bile duct ligated (BDL) rats were treated with TAU (0.5 and 1% w: v in drinking water). Significant increases in the broncho-alveolar lavage fluid (BALF) level of inflammatory cells (lymphocytes, neutrophils, basophils, monocytes, and eosinophils), increased IgG, and TNF-α were detected in the BDL animals (14 and 28 days after the BDL surgery). Alveolar congestion, hemorrhage, and fibrosis were the dominant pulmonary histopathological changes in the BDL group. Significant increases in the pulmonary tissue biomarkers of oxidative stress, including reactive oxygen species formation, lipid peroxidation, increased oxidized glutathione levels, and decreased reduced glutathione, were also detected in the BDL rats. Moreover, significant myeloperoxidase activity and nitric oxide levels were seen in the lung of BDL rats. It was found that TAU significantly blunted inflammation, alleviated oxidative stress, and mitigated lung histopathological changes in BDL animals. These data suggest TAU as a potential protective agent against cholestasis/cirrhosis-related lung injury.

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Lithium Therapy Effects on the Reproductive System

Cited by 6 publications

References 120 publications

The Role of Mitochondrial Impairment and Oxidative Stress in the Pathogenesis of Lithium-Induced Reproductive Toxicity in Male Mice

The Role of Mitochondrial Impairment and Oxidative Stress in the Pathogenesis of Lithium-Induced Reproductive Toxicity in Male Mice

Lithium Enhances the GABAergic Synaptic Activities on the Hypothalamic Preoptic Area (hPOA) Neurons

Taurine mitigates the development of pulmonary inflammation, oxidative stress, and histopathological alterations in a rat model of bile duct ligation

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