Fundamental Toxicological Sciences

Paper Details

Fundamental Toxicological Sciences
Vol. 6 No. 1 January 30, 2019 p.15-23
Original Article
Supplementation with lower doses of EGCg reduces liver injury markers of type 2 diabetic rats
  • Kazuki Mochizuki (Laboratory of Nutritional Physiology, University of Shizuoka, Graduate School of Nutritional and Environmental Sciences / Faculty of Life and Environmental Sciences, University of Yamanashi / mochizukik@yamanashi.ac.jp)
Kazuki Mochizuki 1) 2) , Yu Tan 1) , Yumiko Uchiyama 1) , Takuji Suzuki 3) , Natsuyo Hariya 4) , Toshinao Goda 1)
1) Laboratory of Nutritional Physiology, University of Shizuoka, Graduate School of Nutritional and Environmental Sciences , 2) Faculty of Life and Environmental Sciences, University of Yamanashi , 3) Faculty of Education, Art and Science, Yamagata University , 4) Department of Nutrition, Faculty of Health and Nutrition, Yamanashi Gakuin University
Keywords: (-)-Epigallocatechin-3-gallate, Liver injury, Proinflammatory cytokine, Matrix metalloproteinase, Oxidative stress, Type 2 diabetes
Abstracts

(-)-Epigallocatechin-3-gallate (EGCg), a major catechin in green tea, eliminates reactive oxygen species and development of lifestyle-related diseases. However, excessive EGCg intake could induce adverse effects, particularly liver injury. We examined whether optimal dietary doses of EGCg reduces the risk of liver injuries in non-obese type 2 diabetic Goto-Kakizaki (GK) rats by examining gene expression of the proinflammatory cytokines interleukin (IL)-1β, IL-18 and tumor necrosis factor-α (TNF-α) and fibrosis-related matrix metalloproteinases (MMPs) in the liver. GK rats at 9 weeks of age were fed a control high-fat diet or a high-fat diet containing 0.1%, 0.2% or 0.5% EGCg (w/w) for 25 weeks. Expression of mRNA and proteins related to inflammation were determined by qRT-PCR and western blot analysis, respectively. IL-1β and IL-18 mRNA in the liver were reduced by EGCg supplementation at concentrations of 0.1% and 0.1%-0.2%, respectively, but not at concentrations of 0.2% and 0.5% (IL-1β) or 0.5% (IL-18) EGCg. TNF-α mRNA in the liver was reduced by supplementation with EGCg at concentrations of 0.1%-0.5%. Expression of MMP2 in the liver was reduced by EGCg supplementation at a concentration of 0.2%, but not 0.1% or 0.5%. Importantly, IL-18 protein levels in the liver and serum were reduced by 0.1% EGCg, but not by 0.5%. EGCg supplementation at concentrations from 0.1% to 0.5% did not induce increases in the expression of liver injury marker genes, while low doses (0.1%–0.2%) of EGCg in GK rats reduced expression of injury-associated genes in the liver.