title: Aristolochic acid-induced destruction of organic ion transporters and fatty acid metabolic disorder in the kidney of rats.
abstract: Aristolochic acid (AA) nephropathy exhibits early proximal tubular injury and fatty acid metabolic disorder. In order to study the unrecognized abnormalities of organic ion transporters and fatty acid metabolism indicators in AA nephropathy, Wistar rats were orally administrated with vehicle, 10 and 20mg/kg AA once daily for 7 days, respectively. At day 8, significant reduction of body weight and right kidney weight, as well as elevation of plasma blood urea nitrogen (BUN) levels, renal long-chain fatty acids (LCFAs), non-esterified fatty acids (NEFA) and triglycerides (TG) contents were observed in AA-treated rats, accompanying with down-regulation of renal rOAT1/3, rOCT1/2 and rOCTN1/2 expressions. OCTN2 particularly transports l-carnitine through cell membrane. AA treatment also induced a significant decrease of L-carnitine levels in renal cortex of rats. Down-regulation of peroxisome proliferator-activated receptor alpha (rPPARα) and carnitine acyltransferase 1 (rCPT1), and up-regulation of acetyl coenzyme A carboxylase 1/2 (rACC1/2) in renal cortex were detected in AA-treated rats. These results indicate that alterations of organic ion transportation and fatty acid metabolism are part of AA-induced nephropathy (AAN), contribute to the altered urinary metabolic profile and may lead to further proximal tubule injury in rats.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Han kou Road No. 93, Nanjing, People's Republic of China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Lou
authors.forename: Jianmei
authors.initials: J
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
authors.forename: Xing
authors.initials: X
authors.lastname: Wang
authors.forename: Ruiqing
authors.initials: R
authors.lastname: Jiao
authors.forename: Shuijuan
authors.initials: S
authors.lastname: Wang
authors.forename: Lingdong
authors.initials: L
authors.lastname: Kong
mesh_terms: D000123:Acetyltransferases / Q000235:genetics; D000818:Animals; D034341:Aristolochic Acids / Q000633:toxicity*; D001806:Blood Urea Nitrogen; D002331:Carnitine / Q000032:analysis; D050482:Catecholamine Plasma Membrane Transport Proteins / Q000235:genetics; D003404:Creatinine / Q000097:blood; D005227:Fatty Acids / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins / Q000032:analysis / Q000235:genetics*; D027362:Organic Anion Transport Protein 1 / Q000235:genetics; D029362:Organic Anion Transporters, Sodium-Independent / Q000235:genetics; D027701:Organic Cation Transport Proteins / Q000235:genetics; D000075102:Organic Cation Transporter 2; D051381:Rats; D017208:Rats, Wistar; D000074058:Solute Carrier Family 22 Member 5
chemical_list: D034341:Aristolochic Acids; D050482:Catecholamine Plasma Membrane Transport Proteins; D005227:Fatty Acids; D026901:Membrane Transport Proteins; D027362:Organic Anion Transport Protein 1; D029362:Organic Anion Transporters, Sodium-Independent; D027701:Organic Cation Transport Proteins; D000075102:Organic Cation Transporter 2; C493212:Slc22a1 protein, rat; C100590:Slc22a2 protein, rat; C115441:Slc22a5 protein, rat; C421043:Slc22a6 protein, rat; D000074058:Solute Carrier Family 22 Member 5; C114338:organic anion transport protein 3; C000228:aristolochic acid I; D003404:Creatinine; D000123:Acetyltransferases; C055210:aminoglycoside N1-acetyltransferase; D002331:Carnitine