Department of Hepatology, Kanazawa Medical University, Uchinada, Ishikawa, 920-0293, Japan.
Sci Rep. 2019 Jan 24;9(1):708. doi: 10.1038/s41598-018-37516-4.
The biochemical abnormalities and oxidative stress during pathogenesis of hepatic fibrosis could lead to alteration of trace elements. We studied the alteration of major trace elements during the pathogenesis of N-nitrosodimethylamine (NDMA)-induced hepatic fibrosis in rats. The biochemical and pathological indices of liver functions and hepatic fibrosis were evaluated. Serum and liver levels of copper, iron and zinc were determined using atomic absorption spectrophotometry. Cobalt, manganese, and molybdenum in the serum and liver were estimated by inductively coupled plasma mass spectrometry. Serial administrations of NDMA resulted in decreased serum albumin, biochemical abnormalities, increase of total liver collagen, and well-developed fibrosis and early cirrhosis. Serum and liver zinc content significantly decreased on all the days following NDMA administration. When copper and molybdenum markedly increased in the serum, liver molybdenum decreased dramatically. Both iron and manganese content significantly increased in the liver following NDMA-induced fibrosis. The results of the present study indicate that alteration of trace elements during pathogenesis of hepatic fibrosis is due to metabolic imbalance, biochemical abnormalities, decreased serum albumin, and ascites following NDMA-induced liver injury. The modulation of trace elements during hepatic fibrosis could play a prominent role in progression of the disease.
在肝纤维化发病过程中的生化异常和氧化应激可能导致微量元素的改变。我们研究了在大鼠 N-亚硝二甲胺(NDMA)诱导的肝纤维化发病过程中主要微量元素的变化。评估了肝功能和肝纤维化的生化和病理指标。采用原子吸收分光光度法测定血清和肝脏铜、铁和锌的水平。通过电感耦合等离子体质谱法估计血清和肝脏中的钴、锰和钼。连续给予 NDMA 导致血清白蛋白降低、生化异常、总肝胶原增加以及发达的纤维化和早期肝硬化。在 NDMA 给药后的所有日子里,血清和肝脏锌含量均显著降低。当血清铜和钼显著增加时,肝脏钼含量急剧下降。纤维化诱导后,铁和锰在肝脏中的含量均显著增加。本研究结果表明,肝纤维化发病过程中微量元素的改变是由于 NDMA 诱导的肝损伤后代谢失衡、生化异常、血清白蛋白降低和腹水所致。肝纤维化过程中微量元素的调节可能在疾病进展中发挥突出作用。