Trehalose alleviates oxidative stress-mediated liver injury and Mallory-Denk body formation via activating autophagy in mice

• DOI: 10.1007/s00795-020-00258-2
• Publication Date: 2020-06-25T20:03:36Z
• Authors: Yuichi Honma; Miyuki Sato-Morita; Yuka Katsuki; Hitomi Mihara; Ryoko Baba; Katsuhiko Hino; Akira Kawashima; Toshio Ariyasu; Masaru Harada
• Keywords: 0303 health sciences; Pyridines; Liver Diseases; Administration, Oral; Trehalose; Apoptosis; Mallory Bodies; Endoplasmic Reticulum Stress; 3. Good health; Disease Models, Animal; Mice; Oxidative Stress; 03 medical and health sciences; Liver; Cell Line, Tumor; Autophagy; Hepatocytes; Animals; Humans

Autophagy is a degradation pathway for long-lived cytoplasmic proteins or damaged organelles and also for many aggregate-prone and disease-causing proteins. Endoplasmic reticulum (ER) stress and oxidative stress are associated with the pathophysiology of various liver diseases. These stresses induce the accumulation of abnormal proteins, Mallory-Denk body (MDB) formation and apoptosis in hepatocytes. A disaccharide trehalose had been reported to induce autophagy and decrease aggregate-prone proteins and cytotoxicity in neurodegenerative disease models. But the effects of trehalose in hepatocytes have not been fully understood. We examined the effect of trehalose on autophagy, ER stress and oxidative stress-mediated cytotoxicity and MDB formation in hepatocytes using mice model with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) treatment for 3 months. We administered trehalose by intraperitoneal injection of water containing 10% trehalose (0.02 mg/g body weight) every other day for 3 months. Our results demonstrated that trehalose induced autophagy and reduced ER stress, oxidative stress, MDB formation and apoptosis in hepatocytes of DDC-fed mice by Western blotting and immunostaining analyses. Electron microscopy revealed that trehalose induced autolysosome formation, which located is close to the MDBs. Thus, our findings suggest that trehalose can become a therapeutic agent for oxidative stress-related liver diseases via activating autophagy.