Bio-distribution of Lithium Investigated Using Laser Induced Breakdown Spectroscopy

利用激光誘導擊穿光譜法研究鋰元素的生物學分布

Student thesis: Doctoral Thesis

View graph of relations

Author(s)

Related Research Unit(s)

Detail(s)

Awarding Institution
Supervisors/Advisors
Award date12 Dec 2019

Abstract

Laser induced breakdown spectroscopy (LIBS) measurement methods have been developed in the domain of biological application for multi-elemental analysis of organs and tissue in situ along with complementary spectroscopic methods for reinforcing and calibration purpose. The LIBS measurement methods also complemented the clinical methods to characterize metal-based medicines such as lithium in tissues and organs. Lithium-based medications are used successfully to treat many mental disorders, especially Bipolar disorder (BD). Lithium is taken by approximately 1% of people other than BD, and elevated lithium levels in drinking water are associated with reduced suicide and dementia incidence. However, the therapeutic mechanisms are not well characterized due in part to limitations in detecting lithium in tissues, organs, and cells with small sample mass and volume. Here, we developed LIBS methods for rapid and in situ detection of lithium in biological tissues to better understand lithium mechanisms and help to improve lithium-based treatments. Employed LIBS observed lithium emissions from the rats’ thyroids, salivary glands, mammary glands, and breast milk when lithium was administered orally; affecting multiple functioning elements. The LIBS driven hypothesis mechanisms of such tissues and organs are also formulated. The lithium emission intensity is positively correlated with tissue lithium concentration, which is ~1 ppm.

Lithium’s presence in the breast milk of lithium-treated mother subjects is the likely route of entry to breast-fed infants. This is of concern for the breast-fed infants of medicated mothers (e.g. for BD). We further show that lithium is transmitted through breast-milk to the infant, and trace levels accumulate in the blood, thyroid, kidneys, and brain of infants using LIBS. The infants experience weight gain, reduced blood thyroxine (T4), and elevated blood urea nitrogen, indicating hypothyroidism and kidney impairment. The hypothyroidism persists for a long period after breast-feeding, even though lithium clears from the blood shortly after.

We drew evident based mechanisms on how lithium inhibits iodine uptake by thyroid follicles, initiating a mechanism that reduces the iodination of tyrosine, thyroglobulin cleavage, and thyroid hormone production. Interestingly, the hypothyroidism can be significantly improved by administering supplementary iodine to the medicated mother’s diet throughout lactation. However, the transient lithium toxicity in the kidneys may dominate the pre-renal and intrinsic renal effects of hypothyroidism. These results provide valuable information on lithium use in postpartum and elucidate the mechanisms of lithium. Finally, we suggest LIBS is well suited to characterizing the distribution of lithium and other elements across the body when complemented by other analytical methods. This optical method can potentially be adapted for use in vivo and in humans.

    Research areas

  • Laser induced breakdown spectroscopy, Mass spectrometry, Lithium, Bipolar Disorder, Bio-distribution, Thyroid