Celalettin S Kunak1, Rustem A Ugan2, Elif Cadirci2, Emre Karakus3, Beyzagul Polat4, Harun Un5, Zekai Halici2, Murat Saritemur6, Hasan T Atmaca7, Adem Karaman8. 1. 1 Department of Pharmacology, Ordu University Faculty of Medicine, Ordu, Turkey. 2. 2 Department of Pharmacology, Ataturk University Faculty of Medicine, Erzurum, Turkey. 3. 3 Department of Pharmacology and Toxicology, Ataturk University Faculty of Veterinary Medicine, Erzurum, Turkey. 4. 4 Department of Pharmacology, Ataturk University Faculty of Pharmacy, Erzurum, Turkey. 5. 5 Department of Biochemistry, Agri Ibrahim Cecen University Faculty of Pharmacy, Agri, Turkey. 6. 6 Department of Emergency Medicine, Ataturk University Faculty of Medicine, Erzurum, Turkey. 7. 7 Department of Pathology, Kırıkkale University Faculty of Veterinary Medicine, Kırıkkale, Turkey. 8. 8 Department of Radiology, Ataturk University Faculty of Medicine, Erzurum, Turkey.
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. 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.
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 ureanitrogen 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. 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.
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