title: Melatonin attenuates (-)-epigallocatehin-3-gallate-triggered hepatotoxicity without compromising its downregulation of hepatic gluconeogenic and lipogenic genes in mice.
abstract: (-)-Epigallocatehin-3-gallate (EGCG), a major constituent of green tea, can ameliorate metabolic syndrome at least in part through reducing gluconeogenesis and lipogenesis. Green tea extracts, of which EGCG is a key constituent, have been used for weight loss in humans. A potential adverse effect of high-dose EGCG or green tea extracts is hepatotoxicity. Melatonin, an endogenous antioxidant with a high safety profile, is effective in preventing various types of tissue damage. The current study investigated the influence of melatonin on EGCG-triggered hepatotoxicity and EGCG-downregulated hepatic genes responsible for gluconeogenesis and lipogenesis in mice. We found that (i) melatonin extended survival time of mice intoxicated with lethal doses of EGCG; (ii) melatonin ameliorated acute liver damage and associated hepatic Nrf2 suppression caused by a nonlethal toxic dose of EGCG; (iii) melatonin reduced subacute liver injury and hepatic Nrf2 activation caused by lower toxic doses of EGCG; and (iv) melatonin did not compromise the action of pharmacological doses of EGCG in downregulating a battery of hepatic genes responsible for gluconeogenesis and lipogenesis, including G6Pc, PEPCK, FOXO1α, SCD1, Fasn, leptin, ACCα, ACCβ, GAPT, and Srebp-1. Taken together, these results suggest that the combination of EGCG and melatonin is an effective approach for preventing potential adverse effects of EGCG as a dietary supplement for metabolic syndrome alleviation and body weight reduction.
authors.affiliation: State Key Laboratory of Tea Plant Biology and Utilization, School of Tea & Food Science, Anhui Agricultural University, Hefei, Anhui, China.|International Joint Research Laboratory of Tea Chemistry and Health Effects, Anhui Agricultural University, Hefei, Anhui, China.
authors.forename: Dongxu
authors.initials: D
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Tea Plant Biology and Utilization, School of Tea & Food Science, Anhui Agricultural University, Hefei, Anhui, China.
authors.forename: Yaqing
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Clinical Nutrition, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.
authors.forename: Taotao
authors.initials: T
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Tea Plant Biology and Utilization, School of Tea & Food Science, Anhui Agricultural University, Hefei, Anhui, China.|International Joint Research Laboratory of Tea Chemistry and Health Effects, Anhui Agricultural University, Hefei, Anhui, China.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Wan
authors.affiliation: International Joint Research Laboratory of Tea Chemistry and Health Effects, Anhui Agricultural University, Hefei, Anhui, China.|Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
authors.forename: Chung S
authors.initials: CS
authors.lastname: Yang
authors.affiliation: Department of Cellular and Structural Biology, UT Health Science Center, San Antonio, TX, USA.
authors.forename: Russel J
authors.initials: RJ
authors.lastname: Reiter
authors.affiliation: State Key Laboratory of Tea Plant Biology and Utilization, School of Tea & Food Science, Anhui Agricultural University, Hefei, Anhui, China.|International Joint Research Laboratory of Tea Chemistry and Health Effects, Anhui Agricultural University, Hefei, Anhui, China.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000633:toxicity; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005943:Gluconeogenesis / Q000187:drug effects; D050155:Lipogenesis / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008550:Melatonin / Q000627:therapeutic use*; D051379:Mice; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism
chemical_list: D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D002392:Catechin; C045651:epigallocatechin gallate; D008550:Melatonin
keywords: (-)-Epigallocatehin-3-gallate; gluconeogenesis; hepatotoxicity; lipogenesis; melatonin