| Autor: |
Kaya A; Department of Medical Services and Techniques, Health Services Vocational School, Medical Laboratory Techniques Program, Bayburt University, Bayburt, Turkey., Ceylan AF; Department of Medical Pharmacology, Faculty of Medicine, Ankara Yıldırım Beyazıt University, Ankara, Turkey., Kavutcu M; Department of Medical Biochemistry, Faculty of Medicine, Gazi University, Ankara, Turkey., Santamaria A; Laboratorio de Aminoácidos Excitadores/Laboratorio de Neurofarmacología Molecular y Nanotecnología, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico., Šoltésová Prnová M; Centre of Experimental Medicine, Institute of Experimental Pharmacology & Toxicology, Slovak Academy of Sciences, Bratislava, Slovak Republic., Stefek M; Centre of Experimental Medicine, Institute of Experimental Pharmacology & Toxicology, Slovak Academy of Sciences, Bratislava, Slovak Republic., Karasu Ç; Department of Medical Pharmacology, Cellular Stress Response and Signal Transduction Research Laboratory, Faculty of Medicine, Gazi University, Ankara, Turkey. |
| Abstrakt: |
Inhibiting aldose reductase (ALR2, AR) as well as maintaining a concomitant antioxidant (AO) activity via dual-acting agents may be a rational approach to prevent cellular glucotoxicity and at least delay the progression of diabetes mellitus (DM). This study was aimed at evaluating the dual-acting AR inhibitor (ARI) cemtirestat (CMTI) on tissue oxidative stress (OS) and carbonyl stress (CS) biomarkers in rats exposed to fructose alone (F) or fructose plus streptozotocin (D; type-2 diabetic). D and F rats were either untreated or treated daily with low- or high-dose CMTI, ARI drug epalrestat (EPA) or antioxidant stobadine (STB) for 14 weeks. Malondialdehyde (MDA), glutathione S-transferase (GST), nitric oxide synthase (NOS), and catalase (CAT) were increased in the sciatic nerve of F and D. These increases were attenuated by low doses of CMTI and STB in D, but exacerbated by low-dose EPA and high-dose CMTI in F. STB and CMTI and to a lesser extent EPA improved MDA, protein-carbonyl, GST and CAT in the hearts and lungs of F and D. CMTI and STB were more effective than EPA in improving the increased MDA and protein-carbonyl levels in the kidneys of F and especially D. CMTI ameliorated renal GST inhibition in D. In the lungs, hearts, and kidneys of F and D, the GSH to GSSG ratio decreased and caspase-3 activity increased, but partially resolved with treatments. In conclusion, CMTI with ARI/AO activity may be advantageous in overcoming OS, CS, and their undesirable consequences, with low dose efficacy and limited toxicity, compared to ARI or antioxidant alone. |
