title: Protective effects of quercetin and quercetin-5',8-disulfonate against carbon tetrachloride-caused oxidative liver injury in mice.
abstract: Oxidative stress is one of the major factors in the pathogenesis of liver disease. Quercetin is a plant-based antioxidant traditionally used as a treatment for hepatic injury, but its poor solubility affects its bioavailability. We here report the regulative effects on hepatoprotection and absorption in mice of quercetin sulfation to form quercetin-5',8-disulfonate (QS), a novel synthetic compound. Oral administration of both QS and the parent quercetin at 100, 200 and 500 mg/kg·bw prior to acute CCl4 oxidative damage in mice, effectively attenuated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) activities and hepatic malondialdehyde (MDA) levels (p<0.05), and suppressed the CCl4-induced depletion of glutathione peroxidase (GSH-Px) and total superoxide dismutase (T-SOD). Selective 5',8-sulfation of quercetin increased the hepatoprotective effect, and its relative absorption relative to quercetin (p<0.05) as indicated by an improved 24-hour urinary excretion and a decreased fecal excretion determined by HPLC. These results and histopathological observations collectively demonstrate that quercetin sulfation increases its hepatoprotective effects and absorption in mice, and QS has potential as a chemopreventive and chemotherapeutic agent for liver diseases.
authors.affiliation: School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Yanmang
authors.initials: Y
authors.lastname: Cui
authors.affiliation: School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Han
authors.affiliation: School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Xingbin
authors.initials: X
authors.lastname: Yang
authors.affiliation: School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Sun
authors.affiliation: School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China. yanzhao@fmmu.edu.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000097:blood; D002251:Carbon Tetrachloride / Q000009:adverse effects; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D005979:Glutathione Peroxidase / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D018384:Oxidative Stress / Q000187:drug effects*; D011794:Quercetin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; C574501:quercetin-5',8-disulfonate; D008315:Malondialdehyde; D011794:Quercetin; D002251:Carbon Tetrachloride; D007770:L-Lactate Dehydrogenase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase