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    Nephroprotective potential of carnitine against glycerol and contrast-induced kidney injury in rats through modulation of oxidative stress, proinflammatory cytokines, and apoptosis
    (British Inst Radiology, 2016) Kunak, Celalettin S.; Ugan, Rustem A.; Cadirci, Elif; Karakus, Emre; Polat, Beyzagul; Un, Harun; Karaman, Adem
    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 (GLY1CM); (4) glycerol, CM and 200 mg kg(-1) carnitine (CAR200, Carnitene (R); 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, Omni-paque (TM) T; 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)-beta, transforming growth factor 1 beta, interleukin 1 beta and caspase-3 gene expression decreased compared with the nephrotoxic groups. TNF-alpha and nuclear factor kappa-beta (NF-kappa B) protein expression increased after CM and CAR administration reduced both TNF-alpha and NF-kappa B expressions. Histopathologically, hyaline and haemorrhagic casts and necrosis in proximal tubules increased in the nephrotoxicity groups and decreased in the CAR groups. Conclusion: 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. Advances in knowledge: 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. Advances in knowledge: 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.
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    Tnf-alpha inhibition by infliximab as a new target for the prevention of glycerol-contrast-induced nephropathy
    (Elsevier Science Bv, 2015) Saritemur, Murat; Un, Harun; Cadirci, Elif; Karakus, Emre; Akpinar, Erol; Halici, Zekai; Atmaca, Hasan Tarik
    Contrast medium-induced nephropathy (CIN) remains as a problem with high incidence and mortality rates. The aim of this study is to examine the roles of infliximab (INF) in the glycerol (GLY) and CIN model in rats. The rats were separated into five groups (n=8): Healthy, GLY, GLY+CM, GLY+CM+INF 5 mg/kg intraperitoneally (i.p.), and GLY+CM+INF 7 mg/kg (i.p.). Antioxidant levels in the therapy groups were observed to be quite similar to those in the healthy group. In this study, while the kidney TNF-alpha, TGF-1 beta and Caspase 3 gene expressions' levels increased in the nephrotoxic groups, these levels were found to have decreased in the treatment groups. Moreover, histopathologic examination showed that hyaline, haemorrhagic casts and necrosis were increased in nephrotoxicity group, whereas they decreased in the therapy group. Furthermore, TNF-alpha and NF-kappa B expression were decreased with infliximab administrated groups similar to control group. In conclusion, we suggest that infliximab have protective roles on CIN. (C) 2015 Elsevier B.V. All rights reserved.