Metabolomics evaluation of the effects of green tea extract on acetaminophen-induced hepatotoxicity in mice.
Green tea has been purported to have beneficial health effects including protective effects against oxidative stress. Acetaminophen (APAP) is a widely used analgesic drug that can cause acute liver injury in overdose situations. These studies explored the effects of green tea extract (GTE) on APAP-induced hepatotoxicity in liver tissue extracts using ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry and nuclear magnetic resonance spectroscopy. Mice were orally administered GTE, APAP or GTE and APAP under three scenarios. APAP alone caused a high degree of hepatocyte necrosis associated with increases in serum transaminases and alterations in multiple metabolic pathways. The time of GTE oral administration relative to APAP either protected against or potentiated the APAP-induced hepatotoxicity. Dose dependent decreases in histopathology scores and serum transaminases were noted when GTE was administered prior to APAP; whereas, the opposite occurred when GTE was administered after APAP. Similarly, metabolites altered by APAP alone were less changed when GTE was given prior to APAP. Significantly altered pathways included fatty acid metabolism, glycerophospholipid metabolism, glutathione metabolism, and energy pathways. These studies demonstrate the complex interaction between GTE and APAP and the need to employ novel analytical strategies to understand the effects of dietary supplements on pharmaceutical compounds.
Division of Systems Biology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR 72079, USA.
Yihong
Y
Lu
Jinchun
J
Sun
Katya
K
Petrova
Xi
X
Yang
James
J
Greenhaw
William F
WF
Salminen
Richard D
RD
Beger
Laura K
LK
Schnackenberg
D000082:Acetaminophen / Q000009:adverse effects*; D000818:Animals; D028241:Camellia sinensis / Q000737:chemistry*; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D055432:Metabolomics / Q000379:methods; D051379:Mice; D008815:Mice, Inbred Strains; D010936:Plant Extracts / Q000494:pharmacology*
D005227:Fatty Acids; D010936:Plant Extracts; D000082:Acetaminophen; D005978:Glutathione
3-HB; 3-Hydroxybutyrate; ALP; ALT; APAP; AST; ATP; Acetaminophen; CHOL; CTRL; CYP450; GGT; GLU; GSH; GTE; Green tea extract; Hepatotoxicity; LC/MS; LysoPC; Metabolic profiling; Metabolomics; N-acetyl-p-benzoquinone imine; NAD(+); NAPQI; NMR; PC; PCA; PLS-DA; QC; QTOF-NEG; QTOF-POS; ROS; TBILI; TRI; ULN; UPLC/MS; UPLC/QTof-MS; acetaminophen; adenosine-5′-triphosphate; alanine aminotransferase; alkaline phosphatase; aspartate aminotransferase; cholesterol; control; cytochrome P450; glucose; glutathione; green tea extract; liquid chromatography/mass spectrometry; lysophosphatidylcholine; nicotinamide adenine dinucleotide; nuclear magnetic resonance; partial least squares-discriminant analysis; phosphatidylcholine; principal component analysis; quadrupole time-of-flight negative mode; quadrupole time-of-flight positive mode; quality control; reactive oxygen species; total bilirubin; triglycerides; ultra performance liquid chromatography mass spectrometry; ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry; upper limit of normal; γ-glutamyl transferase