title: Nephroprotective potential of carnitine against glycerol and contrast-induced kidney injury in rats through modulation of oxidative stress, proinflammatory cytokines, and apoptosis.
abstract: OBJECTIVE
  Contrast media (CM) are a major cause of nephropathy in high-risk patients. The aim of this study was to examine the effects of carnitine (CAR) in advanced nephrotoxicity due to CM administration in rats with glycerol-induced renal functional disorder.
  
  
  METHODS
  40 rats were divided randomly into five groups (n = 8): (1) healthy group; (2) glycerol only (GLY); (3) glycerol and CM (GLY + CM); (4) glycerol, CM and 200 mg kg(-1) carnitine (CAR200, Carnitene(®); Sigma-tau/Santa Farma, Istanbul, Turkey); and (5) glycerol, CM and 400 mg kg(-1) carnitine (CAR400). Kidney injury was induced with a single-dose, intramuscular injection of 10 ml kg(-1) body weight (b.w.) of GLY. CAR was administered intraperitoneally. CM (8 ml kg(-1) b.w. iohexol, Omnipaque™; Opakim Medical Products, Istanbul, Turkey) was infused via the tail vein to the rats in Groups 3-5.
  
  
  RESULTS
  l-carnitine administration significantly decreased serum creatinine and blood urea nitrogen levels. Superoxide dismutase and glutathione activity increased significantly in the treatment groups compared with the nephrotoxic groups. CAR400 significantly reduced malondialdehyde levels to healthy levels. In the treatment groups, tumour necrosis factor (TNF)-α, transforming growth factor 1β, interleukin 1β and caspase-3 gene expression decreased compared with the nephrotoxic groups. TNF-α and nuclear factor kappa-beta (NF-κB) protein expression increased after CM and CAR administration reduced both TNF-α and NF-κB expressions. Histopathologically, hyaline and haemorrhagic casts and necrosis in proximal tubules increased in the nephrotoxicity groups and decreased in the CAR groups.
  
  
  CONCLUSIONS
  The results reveal that l-carnitine protects the oxidant/antioxidant balance and decreases proinflammatory cytokines and apoptosis in CM-induced nephrotoxicity in rats with underlying pathology.
  
  
  CONCLUSIONS
  Depending on the underlying kidney pathologies, the incidence of CM-induced nephropathy (CIN) increases. Therefore, this is the best model to represent clinically observed CIN.
authors.affiliation: 1 Department of Pharmacology, Ordu University Faculty of Medicine, Ordu, Turkey.
authors.forename: Celalettin S
authors.initials: CS
authors.lastname: Kunak
authors.affiliation: 2 Department of Pharmacology, Ataturk University Faculty of Medicine, Erzurum, Turkey.
authors.forename: Rustem A
authors.initials: RA
authors.lastname: Ugan
authors.affiliation: 2 Department of Pharmacology, Ataturk University Faculty of Medicine, Erzurum, Turkey.
authors.forename: Elif
authors.initials: E
authors.lastname: Cadirci
authors.affiliation: 3 Department of Pharmacology and Toxicology, Ataturk University Faculty of Veterinary Medicine, Erzurum, Turkey.
authors.forename: Emre
authors.initials: E
authors.lastname: Karakus
authors.affiliation: 4 Department of Pharmacology, Ataturk University Faculty of Pharmacy, Erzurum, Turkey.
authors.forename: Beyzagul
authors.initials: B
authors.lastname: Polat
authors.affiliation: 5 Department of Biochemistry, Agri Ibrahim Cecen University Faculty of Pharmacy, Agri, Turkey.
authors.forename: Harun
authors.initials: H
authors.lastname: Un
authors.affiliation: 2 Department of Pharmacology, Ataturk University Faculty of Medicine, Erzurum, Turkey.
authors.forename: Zekai
authors.initials: Z
authors.lastname: Halici
authors.affiliation: 6 Department of Emergency Medicine, Ataturk University Faculty of Medicine, Erzurum, Turkey.
authors.forename: Murat
authors.initials: M
authors.lastname: Saritemur
authors.affiliation: 7 Department of Pathology, Kırıkkale University Faculty of Veterinary Medicine, Kırıkkale, Turkey.
authors.forename: Hasan T
authors.initials: HT
authors.lastname: Atmaca
authors.affiliation: 8 Department of Radiology, Ataturk University Faculty of Medicine, Erzurum, Turkey.
authors.forename: Adem
authors.initials: A
authors.lastname: Karaman
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001806:Blood Urea Nitrogen; D002331:Carnitine / Q000494:pharmacology*; D003287:Contrast Media / Q000633:toxicity*; D003404:Creatinine / Q000097:blood; D016207:Cytokines / Q000097:blood*; D005990:Glycerol / Q000633:toxicity*; D007150:Immunohistochemistry; D007472:Iohexol / Q000633:toxicity*; D007674:Kidney Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D003287:Contrast Media; D016207:Cytokines; D007472:Iohexol; D003404:Creatinine; D005990:Glycerol; D002331:Carnitine