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Öğe Effects of propolis, caffeic acid phenethyl ester, and pollen on renal injury in hypertensive rat: An experimental and theoretical approach(Wiley, 2017) Salmas, Ramin Ekhteiari; Gulhan, Mehmet Fuat; Durdagi, Serdar; Sahna, Engin; Abdullah, Huda I.; Selamoglu, ZelihaThe objective of this study was to evaluate the antioxidant effects of propolis, caffeic acid phenethyl ester (CAPE; active compound in propolis), and pollen on biochemical oxidative stress biomarkers in rat kidney tissue inhibited by N-nitro-L-arginine methyl ester (L-NAME). The biomarkers evaluated were paraoxonase (PON1), oxidative stress index (OSI), total antioxidant status (TAS), total oxidant status (TOS), asymmetric dimethylarginine (ADMA), and nuclear factor kappa B (NF-B). TAS levels and PON1 activity were significantly decreased in kidney tissue samples in the L-NAME-treated group (P<0.05). The levels of TAS and PONI were higher in the L-NAME plus propolis, CAPE, and pollen groups compared with the L-NAME-treated group. TOS, ADMA, and NF-B levels were significantly increased in the kidney tissue samples of the L-NAME-treated group (P<0.05). However, these parameters were significantly lower in the L-NAME plus propolis, CAPE, and pollen groups (P<0.05) compared with rats administered L-NAME alone (P<0.05). Furthermore, the binding energy of CAPE within catalytic domain of glutathione reductase (GR) enzyme as well as its inhibitory mechanism was determined using molecular modeling approaches. In conclusion, experimental and theoretical data suggested that oxidative alterations occurring in the kidney tissue of chronic hypertensive rats may be prevented via active compound of propolis, CAPE administration.Öğe The effects of pollen, propolis, and caffeic acid phenethyl ester on tyrosine hydroxylase activity and total RNA levels in hypertensive rats caused by nitric oxide synthase inhibition: experimental, docking and molecular dynamic studies(Taylor & Francis Inc, 2018) Salmas, Ramin Ekhteiari; Durdagi, Serdar; Gulhan, Mehmet Fuat; Duruyurek, Merve; Abdullah, Huda I.; Selamoglu, ZelihaThe objective of the present study was to evaluate the effects of propolis, pollen, and caffeic acid phenethyl ester (CAPE) on tyrosine hydroxylase (TH) activity and total RNA levels of N-nitro-L-arginine methyl ester (L-NAME) inhibition of nitric oxide synthase in the heart, adrenal medulla, and hypothalamus of hypertensive male Sprague dawley rats. The TH activity in the adrenal medulla, heart, and hypothalamus of the rats was significantly increased in the L-NAME group vs. control (p<0.05). Treatment with L-NAME led to a significant increase in blood pressure (BP) in the L-NAME group compared to control (p<0.05). These data suggest that propolis, pollen, and CAPE may mediate diminished TH activity in the heart, adrenal medulla, and hypothalamus in hypertensive rats. The decreased TH activity may be due to the modulation and synthesis of catecholamines and BP effects. In addition, the binding mechanism of CAPE within the catalytic domain of TH was investigated by means of molecular modeling approaches. These data suggest that the amino acid residues, Glu429 and Ser354 of TH may play a pivotal role in the stabilization of CAPE within the active site as evaluated by molecular dynamics (MD) simulations. Gibbs binding free energy (G(binding)) of CAPE in complex with TH was also determined by post-processing MD analysis approaches (i.e. Poisson-Boltzmann Surface Area (MM-PBSA) method).