title: Effects of antioxidants on drug absorption in in vivo intestinal ischemia/reperfusion.
abstract: Ischemia/reperfusion (I/R) injury must be overcome in order to succeed in small intestinal transplantation. Reactive oxygen species (ROS) are generated by I/R, and they induce lipid peroxidation which is one of the causes of mucosal lesion. We previously reported the protection effects of antioxidants to I/R injury in the in vitro study. In the present study, we examined the inhibitive effect of antioxidants on intestinal I/R injury in the in vivo study. Intestinal ischemia was induced in Wistar/ST rats using the spring scale and the surgical suture for 1 h, followed by reperfusion for 1 h. We used 4,5-dihydroxy-1,3-benzene-disulfonic acid (Tiron), astaxanthin (ATX) and epigallocatechin gallate (EGCG) as antioxidants. The inhibitive effects on mucosal lesion, opening of TJ and decrease in protein expression level of P-gp by in vivo intestinal I/R were admitted by three kinds of antioxidant. Tiron and EGCG inhibited P-gp function but ATX did not. Therefore, for the use of P-gp substrate like immunosuppressants after the intestinal transplantation, ATX, which does not inhibit P-gp is considered to be effective for intestinal I/R injury.
authors.affiliation: Department of Drug Absorption and Pharmacokinetics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan. takizawa@toyaku.ac.jp
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Takizawa
authors.forename: Takuya
authors.initials: T
authors.lastname: Kitazato
authors.forename: Hisanao
authors.initials: H
authors.lastname: Kishimoto
authors.forename: Mikio
authors.initials: M
authors.lastname: Tomita
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hayashi
mesh_terms: D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt / Q000494:pharmacology; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D003911:Dextrans / Q000493:pharmacokinetics; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D007422:Intestines / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D024341:Xanthophylls / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000975:Antioxidants; D003911:Dextrans; D024341:Xanthophylls; C015219:fluorescein isothiocyanate dextran; D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt; D002392:Catechin; C005948:astaxanthine; C045651:epigallocatechin gallate; D016650:Fluorescein-5-isothiocyanate