title: Activation of complement system in kidney after ketoprofen-induced kidney injury in sheep.
abstract: BACKGROUND
  Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat inflammatory pain in humans and animals. An overdose of an NSAID is nephrotoxic and can lead to acute kidney injury (AKI). Complement activation occurs in several types of renal disorders with proteinuria. The aim of this study was to investigate whether complement system becomes activated in kidneys after a high dose of NSAID. Kidney tissue and urine samples were collected from six sheep with ketoprofen-induced AKI and from six healthy control sheep. The localization of complement proteins in kidney tissue was carried out using immunohistochemical stainings, and excretion of C3 was tested by immunoblotting.
  
  
  RESULTS
  The complement system was found to become activated in the kidney tissue as demonstrated by positive immunostaining for C1q, C3c, C4c, C5, C9 and factor H and by Western blotting analysis of C3 activation products in urine samples in sheep with AKI.
  
  
  CONCLUSIONS
  Our results thus suggest that the alternative complement pathway is activated, and it may contribute to the acute tubular injury seen in the kidneys of NSAID-induced AKI sheep. Inhibition of complement activation may serve as potential therapeutic target for intervention in drug-induced AKI.
authors.affiliation: Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, P. O. Box 56, FI-00014, Helsinki, Finland. mari.palviainen@helsinki.fi.
authors.forename: Mari J
authors.initials: MJ
authors.lastname: Palviainen
authors.affiliation: Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 66, FI-00014, Helsinki, Finland. sami.junnikkala@helsinki.fi.
authors.forename: Sami
authors.initials: S
authors.lastname: Junnikkala
authors.affiliation: Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, P. O. Box 56, FI-00014, Helsinki, Finland. marja.raekallio@helsinki.fi.
authors.forename: Marja
authors.initials: M
authors.lastname: Raekallio
authors.affiliation: Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, P.O. Box 21, FI-00014, Helsinki, Finland. seppo.meri@helsinki.fi.
authors.forename: Seppo
authors.initials: S
authors.lastname: Meri
authors.affiliation: Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, P. O. Box 56, FI-00014, Helsinki, Finland. outi.vainio@helsinki.fi.
authors.forename: Outi
authors.initials: O
authors.lastname: Vainio
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000503:physiopathology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000652:urine; D015153:Blotting, Western / Q000662:veterinary; D003165:Complement System Proteins / Q000378:metabolism* / Q000652:urine; D005260:Female; D007150:Immunohistochemistry / Q000662:veterinary; D007660:Ketoprofen / Q000009:adverse effects* / Q000652:urine; D007668:Kidney / Q000293:injuries; D012756:Sheep; D012757:Sheep Diseases / Q000139:chemically induced / Q000503:physiopathology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003165:Complement System Proteins; D007660:Ketoprofen