Effects of lithium on stress hormones and liver function in vivo and in vitro

摘要

Bipolar disorder is the sixth leading reason of disability all over the world Lithium salt a common drug for bipolar disorder has a narrow therapeutic index As such lithium poisoning occurs frequently in patients with long-term use The toxicity of lithium on central nervous renal endocrine cardiovascular systems has been extensively studied Only few but controversial results were reported regarding its effects on stress hormones and liver function In this study we aimed to establish a solid phase extraction-based liquid chromatography tandem mass spectrometry (SPE-LC-MS/MS) method for the measurement of urinary catecholamines and metanephrines and to investigate lithium-induced alterations on stress hormones Meanwhile lithium-induced cytotoxicity and liver function were investigated In addition the effects of valproic acid (VPA) another medication in bipolar disorder frequently in combination with lithium as polytherapy on stress hormones and liver function were also examined AML12 and FL83B hepatocytes treated with lithium exerted significantly enhanced oxidative stress and decreased cell viability at a dose- and time-dependent manner starting at lithium concentration of 1 25 mM Also lithium treatment significantly decreased mitochondrial membrane potential (MMP) at a dose-dependent manner beginning at lithium concentration of 1 25 mM Additional N-acetylcysteine (NAC) administration at 10 mM recovered the lithium-induced liver damage C57BL/6 mice intraperitoneally injected with 100 mg/kg lithium for 4 weeks demonstrated twice urine volume compared to the control group Lithium treatment decreased excretion of urine norepinephrine (mean value 322 μg/g crea vs 439 μg/g crea p

獎項日期	2016 8月 31
原文	English
監督員	Shu-Chu Shiesh (Supervisor)