alpha-Tocopherol supplementation reduces inflammation and apoptosis in high cholesterol mediated nonalcoholic steatohepatitis.

Demirel-Yalciner T., Sozen E., Ozaltin E., Sahin A., Ozer N.

BioFactors (Oxford, England), cilt.47, ss.403-413, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 47
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1002/biof.1700
  • Dergi Adı: BioFactors (Oxford, England)
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, EMBASE, Environment Index, Food Science & Technology Abstracts, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.403-413
  • Anahtar Kelimeler: apoptosis, fibrosis, high cholesterol diet, inflammation, NASH, alpha-tocopherol, FATTY LIVER-DISEASE, HEPATIC STELLATE CELLS, OXIDATIVE STRESS, VITAMIN-E, LIPID OXIDATION, C-JUN, EXPRESSION, AUTOPHAGY, NAFLD, ACIDS
  • Marmara Üniversitesi Adresli: Evet

Özet

Inflammation and apoptosis signaling are crucial steps in the progression from nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis (NASH). Alpha-tocopherol, the most active form of vitamin E, is an important modulator of signaling mechanisms, but its involvement to cholesterol-induced NASH pathogenesis remains poorly defined. Herein we have reported a novel effect of alpha-tocopherol in the transition from hepatic steatosis to NASH. High cholesterol diet alone (without alpha-tocopherol) in rabbits elevated NASH development as indicated by increased inflammatory response, apoptotic activity and liver fibrosis. Such elevation results from induction of signaling mechanisms since the expressions of IL1 beta, phospho c-Jun/c-Jun ratio, JNK, caspase 9, CHOP and Bax were increased, and recruitment of macrophage, alpha-smooth muscle actin (alpha-SMA) and COL1A1 into the liver tissue were induced. Alpha-tocopherol supplementation inhibited inflammatory response, apoptosis and fibrosis development without affecting lipid accumulation in high cholesterol-induced NASH. Specifically, alpha-tocopherol lowered the inflammatory level as observed by reduced macrophage infiltration and JNK/c-Jun signaling. Lower inflammatory status co-occurred with the reduction of CHOP and Bax expressions as well as fibrosis-related COL1A1 and alpha-SMA levels. Taken together, alpha-tocopherol supplementation inhibits cholesterol-induced NASH development by lowering JNK/c-Jun/inflammation axis in addition to JNK/CHOP/apoptosis signaling, which might contribute to resistance against NAFLD/NASH transition.